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DEVELOPMENT OF A HEALTH-RELATED QUALITY OF LlFE (HRQL) INSTRUMENT FOR NAUSEA AND
VOMlTlNG IN PREGNANCY (NVP)
Kiran Chandra
A thesis subrnitted in conformity with the requirernents for the degree of M.Sc.
Graduate Departrnent of Pharrnacology University of Toronto
O Copyright by Kiran Chandra (2000)
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ABSTRACT
Development of a Health-Related Quality of Life (HRQL) Instrument for Nausea and Vomiting in Pregnancy (NVP) M.Sc. (2000) Kiran Chandra Graduate Department of Phannacology University of Toronto
This thesis examined impairment of quality of life of Nausea and
Vomiting in Pregnancy (NVP) patients. Many interventions are geared to
resolving patients' symptorns but don't take into account their impact on Health-
Related Quality of Life (HRQL). Our objective was to develop a disease
specific instrument for measuring HRQL in NVP patients. Items potentially
affecting HRQL of patients were identified based on women's responses.
research experts and Medline search. A separate sample of 500 wornen
identified items probiematic and rated their importance. Areas of quality of life
impairment included NVP symptoms, responses to environrnental stimuli,
socialfdomestic/occupational limitations and emotional dysfunction. Results
were explored using a factor analysis and domains of dysfunction were chosen
eliminating redundant questions. The questionnaire includes areas of quality of
life impairment important to NVP patients. It has been designed to assess
changes within subjects to be used as a measure of outcome in NVP clinical
trials.
Special thanks to:
Lauren Griffith, for the factor analysis,
Caroline Maltepe, Yvette Navioz, Adrienne Einarson and Gordana Atanackovic. rny NVP research team.
Dr. Shinya Ito, my advisor,
Drs. Gideon Koren & Laura Magee, my supervisors,
and finally my family and friends who have supported and encouraged me for the past 2 years of my graduate schooling and work.
iii
TABLE OF CONTENTS
. . ......................................................................... ABSTRACT 11
........................................................ ACKNOWLEDGEMENT iii
........................................... LIST OF TABLES ...w..a.D....m... vi
LIST OF FIGURES ..................... ... .................................. vii
... LIST OF APPENDICES .......... ... ......................................... VIII
1.1 STATEMENT OF PROBLEM ...................................... 1 1.2 OBJECTIVE ............................................................ 3 1.3 HYPOTHESIS ......................................................... 3
SECTION 2 REVIEW OF THE LITERATURE .............................. 4 DEFINITION OF NVP ......................... .. .................. 4 EPIDEMIOLOGY OF NVP ......................................... 5 PATHOGENESIS ..................................................... 6
2.3.1 Endocrinology ............................................................ 8 2.3.2 Gastrointestinal Motility .............................................. 10 2.3.3 Lipid Metabolism ...................................................... 12
................................................ 2.3.4 Psychological Factors 13 2.3.5 Vitamin B6 Deficiency ................................................. 1 4
OUTCOME ............................................................ 14 THERAPY FOR NVP .............................................. 16 QUALITY OF LIFE .......................................................... 1 7 1 MPACT ON WOMEN'S LIVES ................................. 20 SUMMARY ..................................................................... 22
SECTION 3 METHODSm..Dmmmm.wm .......m....*.rn.........m....rn............. ma23 3.1 ITEM GENERATION ............................................... 23
3.2 SOURCES OF INFORMATION ................................. 23 3.3 ITEM REDUCTION ................................................. 26 3.4 STUDY PROCEDURES .......................................... 26 3.5 ANALYSIS .......................................................... 28
........................................... 3.6 ITEM PRESENTATION 29 3.7 SAMPLE SIZE ................. .... ...... .. ...........+........m.. 29 3.8 ETHICS .............................................................. 30
SECTION 4 RESULTS*am**a*ma****mm**omo* * . a * * o o . . . . . . . . . . * * * m * m . . r n r n m . . m m m * m m a Z l
4.1 RECRUITMENT FOR THE ITEM REDUCTION PHASE.31 .................................. 4.2 MATERNAL DEMOGRAPHICS -33
4.3 OVERALL IMPACT SCORES ......................................... 38 *............. .................................... 4.4 FACTOR AN ALY S I S .. -54
4.4.1 Factor 1 ................................................................. -58 4.4.2 Factor 2 .................................................................. 58 4.4.3 Factor 3 .................................................................. 59 4.4.4 Factor 4 .................................................................. 59
4.5 NVP-HRQL QU EsTl ONNAI RE ................................. 59
SECTION 5 DISCUSSION AND CONCLUSIONSmmmm. 0 0 l a * o a a mma63
SECTION 6 FUTURE D I R E C T I O N S * * = o . m * ~ * ~ m m ~ m m m m m m m m m m m m m m o m ~ m e m m m * m m m 6 8 6.1 PRE-TESTING OF NVP-HRQL QUESTIONNAIRE ......... 68 6.2 VALlDlTY AND RESPONSIVENESS ...... ............ ........... -68 6.3 SUMMARY ........................................................... 69
SECTION 7 R E F E R E N C E S a a . a a m * m ~ ~ m ~ * * * ~ e * a ~ o * m m * m o m m m m m * * m m m m m ~ m m ~ m m m m m m m 7 O
LIST OF TABLES
Table l. Table II.
Table III. Table IV.
Tabie V.
Table VI. Table VII.
Table VIII.
Table IX.
Table X.
Table XI.
Table XII.
Table Xlll.
Maternai Characteristics of 500 Patients. ............................... -34 2 2.0 scoring items of the 195 items presented to patients with NVP.. ...................................................................................... -38 Order of Overall Importance of items by Subgroup ................... 41 Mean Overall Impact by Subgroup. .......................................... 51
4 - Factor Solution using a Varimax Rotation for ail ô6 items with .............................................................. Impact Score 2 2.0.. 5 7
Items in their Domains that made it to the Final Questionnaire..Gl 3 - Factor Solution using a Varimax Rotation for al1 66 items with Impact Score 1 2.0.. ............................................................. .XXIV Rotated Factor Loadings for a 3 - Factor Model for all 66 items with Impact Score 2 2.0.. ................................................... XXV Rotated Factor Loadings for a 4 - Factor Model for all 66 items with Impact Score 2 2.0.. ................................................. .XXVII
Pearson Correlation Coefficients for the 15 items with lmpact ................ Score 1 2.0 for Factor 1 for the 4 - Factor Model ..XXX
Pearson Correlation Coefficients for the 1 1 items with lmpact ................ Score 2 2.0 for Factor 2 for the 4 - Factor Model XXXV
Pearson Correlation Coefficients for the 5 items with lmpact Score ........................ 2 2.0 for Factor 3 for the 4 - Factor Mode1 XXXVll
Pearson Correlation Coefficients for the 2 items with lmpact Score 2 2.0 for Factor 4 for the 4 - Factor Model.. .................... XXXVIII
Figure 1. Recruitment Charts of 500 women between 1997 and 1999.. ................................................................................ 31
Figure 2. Scree Plot of Eigenvalues for al1 66 items with Impact Sores >= 2.0.. ....................................................................... ..XXIX
vii
LIST OF APPENDICES
.............................................. Appendix A. Item Reduction Questionnaire.. ..l ........................ Appendix B. McMaster Telep hone Interview Guidelines.. .XIX
Appendix C. Five-Point Likert Scale. ............................................................. .XXI Appendix D. Factor Analysis Results ........................................................... 1 II Appendix E. Nausea and Vomiting in Pregnancy Health-Related Quality of Life
Questionnaire .................................................................... .XXXIX
Section 1 INTRODUCTION
1.1 STATEMENT OF PROBLEM
Although Nausea and Vomiting in Pregnancy (NVP) affects more than
half of pregnant women. it is largely ignored and neglected in terms of medical
research into the development of new treatment modalities. Presently, there is
no tool with which to assess the severity of symptoms of NVP, further
hampering any attempt to study the effectiveness of different treatment
modalities.
The research group at the Motherisk Program is one of very few to focus
on NVP in an attempt to improve the health and quality of life of millions of
women every year. The development of the proposed new measurement tool is
key for any future research in this area.
Clinical trials in NVP have focused. in general, on physiological
measures of outcome such as improvement in the severity of NVP. The
primary outcome has been restricted to changes in conventional, clinical,
physical symptoms and has not taken into account the impact of the symptorns
and other aspects of the disease on the patients' lives. In this study we
evaluated impairment of quality of life in NVP patients, with stratification for
several possible detemiinants of impact scores such as age, parity, smoking,
education, occupation, NVP severity, nausea episodes, vomithetch episodes,
anti-emetic use and non-drug use. By using only physical symptoms of NVP as
outcome measures for drug therapy, one ignores the fact that the relationship
between the occurrence/severity of nauseahomiting and the distress caused by
that nauseafvomiting is not predictable'. Secondly, assessing only the severity
of nausea andfor vomiting may miss not only therapeutic effects of potential
importance to patients (e.g.. the ability to work), but also adverse effects that
might make therapy less desirable to patients (e.g.. drowsiness from
antihistarninic anti-emetics).
As NVP is rarely life - threatening and certainly time - limited, most
treatment for NVP should be aimed at improving the quality of a woman's life.
Many medical intewentions are designed to improve the quality rather than to
extend a patient's life. Therefore, a rneasure of quality of life is required to
assess the overall benefit of any given intervention. Although there are a
number of generic quality of life rneasures in existence, there is no NVP -
specific or even pregnancy - specific quality of life measure in existence. There
are reasons to believe that such a measure is needed. Firstly. disease - or
patient - specific rneasures are more likely to detect small, clinically important
changes in quality of life due to specific medical conditions. Secondly, patients
with NVP are likely to have unique concems. such as fears about the fetal
safety of anti-emetic medication. Other concems may be fear of going out due
to exposure to smells or foods that may trigger their symptoms which in tum
leads to embarrassrnent in the case that they vomit or retch in public. These
issues are neglected and not addressed when physical measures are the only
outcorne in clinical triais. Therefore, there is a need for a specific, evaluative
instrument for measurement of health - related quality of life (HRQL) in NVP.
1.2 OB J ECTlVE
The objective of this thesis was to deveiop a questionnaire capable of
measuring change in HRQL symptoms of NVP over time, in individual patients.
This change can occur in areas of dysfunction such as physical, emotional,
social, occupational or others. The instrument is intended for use as an
evaluative tool in therapeutic intervention trials for NVP.
1.3 HYPOTHESIS
NVP has a major impact on the occupational function and HRQL of
women. Women with NVP have unique concerns and issues and since
pregnant women's qualitative experiences with nausea and vomiting have not
been adequately docurnented in the medical literature, health given may be
unable to advise and support them appropriately.
Section 2 REVIEW OF THE LITERATURE
2.1 DEFINITION OF NVP
Nausea can be defined as an unpleasant sensation usually preceding
vomiting2. It may be precipitated by several conditions such as motion
sickness, diseases of the central nervous system, gastrointestinal disturbances
and pregnancy. It may also be triggered due to sight or odor of obnoxious
matter, conditions or mental images2. Vorniting is a reflex integrated in the
medulla oblongata and it occurs when rnaterial is ejected from the stomach
through the mouth and retching can be defined as an intense rhythmic
contraction of the respiratory and abdominal muscles that may precede or
accompany vomiting2. Many stimuli can induce vomiting such as gastric
mucosal irritation (e.g. alcohol), stimulating the equilibration organs through the
inner ear (motion sickness), severe pain. poisons, irradiation effects (tumor
therapy), elevated intra - cranial pressure (brain edema), hemorrhage or tumor
in the brain region and pregnancy2. These triggers stimulate the vomiting
center in the medulla oblongata and chemoreceptors in the vicinity of the
vomiting center in the area postrema2.
Due to the many causes of nausea and vomiting, NVP becomes a
diagnosis of exclusion after history, physical and routine laboratory
investigations have mled out structural (e.g., gastrointestinal obstruction),
central nervous system (e.g., space-occupying lesion), hormonal (e.g.,
thyrotoxicosis), metabolic (e.g., renal failure), toxicological (e.g., narcotics), or
psychiatric (e.g., bulimia) causes of nausea or vomiting3. The diagnosis of NVP
is confirmed by symptoms that are self-limited, usually to the first and eariy
second trimesters, but definitely to pregnancy itseif.
2.2 EPIDEMIOLOGY OF NVP
Descriptions of NVP dates back to writings from the 2nd century AD^.
NVP afflicts up to 80% of pregnant women to greater or lesser degrees5.
Approximately 50% of women have nausea and vomiting, whereas
approximately 30% have only nausea5. Symptoms are usually self - limited in
duration (Le., to 7-12 weeks' gestation), although 9% of wornen continue to
have symptoms beyond 20 weeks5. Fewer than 1% of pregnant wornen
develop hyperemesis gravidarum (HG) characterized by severe p hysical
symptoms andior medical complications (e.g., dehydration, electrolyte
imbalance) requiring admission to hospita15. Based on data from multiparous
patients, approximately one third of women will have different symptoms (i.e.,
severity or duration) in subsequent pregnancies4.
NVP is most commonly reported in Western countrîes. in predominantly
urban as compared with rural areas6. It is rarely seen in African, Native
American, Eskimo, and some Asian populations with the exceptions of
Japanese and Chinese women6.
There are different factors that have been hypothesized to be associated
with NVP which range from low socioeconornic status7 to younger matemal
age8. Certain items in the reproductive history rnay also influence the
occurrence of NVP such as NVP in previous pregnanciesseg, nulliparityl*,
unplanned pregnancy'l. history of infertility7, size of placentag. primigravidas8,
multiple gestation8 and prior intolerance to oral contraceptive^'^. Alcohol and
tobacco consumption are also postulated to affect N V P ~ * ~ ~ " . However none of
these factors allow for prediction of the occurrence of NVP in an individual
patient and none contribute to Our understanding of the underlying
pathogenesis.
2.3 PATHOGENESIS
The pathogenesis of NVP is poorly understood. and etiologies abound13.
This may be due, at least in part, to the fact that radiological and
phamacological investigations have been hampered by concems about
teratogenicity, especially during the first trimester of pregnancy. There is no
proven role for gestational or other hormones. No correlation has been found
between the severity of NVP and levels of human chorionic gonadotropin
(hCG), despite the fact that hCG levels peak during the first trimester, and
conditions associated with high levels of hCG (e.g.. molar pregnancy. multiple
gestation) are associated with NVP'~. Neither estrogen nor 1 7-progesterone
levels have been correlated with NVP. Although a correlation has been found
with estradiol ~evels'~. Raised thyroid hormone levels have been proposed, but
not consistently ~ b s e r v e d ' ~ ~ ' ~ ~ ' ~ ~ ' ? When observed it can be unclear as to
whether the patient has thyrotoxicosis which is causing the nausea and
vomiting or whether hCG is stirnulating the thyroid directly since hCG and TSH
are homologous. NVP has also been proposed to be the result of blunted
autonornic nervous system function or dysregulation of gastric rhythms
measured by electrogastrograms (ECGS)~'. Psycholog ical factors, such as
depression, anxiety, and eating disorders have also been observed however, it
is not clear whether these preceded or resulted from severe
symptomatology? NVP has also been associated with vitamin B6
de fi ci en^^^^. This has led to changes in therapy through optimization of
materna1 nutrition.
Although biological factors have been suggested to be associated with
NVP, such as carbohydrate metabolism, vitamin deficiencies and endocrine
disturbances, the etiology of NVP has not been established, and is likely to be
multifactorial. Idiopathic NVP must be distinguished from NVP of known
etiology i.e. hydatidiform mole, multiple gestation. Non - pregnancy related, e.g.
GI, genitourinary, CNS, toxidmetabolic causes must also be considered and
ruled out. We do not know what causes NVP eventhough there is strong
evidence that gestational hormones rnay play a role in its et io~ogy~~ '~* '~ . As a
result it is possible that patients with different undedying abnonnalities rnay
respond differently to various therapies which can be targeted more
appropriately.
2.3.1 Endocrinology
hCG levels peak in the first trimester when the frequency of nausea and
vomiting peaksq4. The relationship between NVP and hCG levels however is
controversial. The incidence of hyperemesis is hig her in multiple gestation and
in mole hydatidiform disease. Thus a relationship to the level of hCG has been
postulated. Reports have noted that women with NVP had higher
concentrations of urinary and senim hCG than asymptomatic womed4. On
average women suffering from NVP have heavier placentaeg. Other reports
showed no relationship between serum hCG levels in women with nomal or
rnolar pregnancies during the first 16 weeks of gestation and the frequency or
intensity of nausea and vomitingZ4. Although women with molar pregnancies
had 5 to 10 times higher levels of serurn hCG than women with nomal
pregnancies, no significant differences in these levels was noted whether
nausea and vorniting was present or absed4.
With regards to estrogens, we know that women who did not tolerate oral
contraceptives because of side effects including nausea had a higher incidence
of NVP due to high levels of estrogen12. Further support for this causation are
reported associations between NVP and nulliparous, overweight and non -
smoking women, al1 of whom have elevated urinary and circulating estrogen
l e v e ~ s ~ ~ but at present the role of estrogen is unknown.
Progesterone is also believed to be important because it decreases
smooth muscle activity, potentially prolonging gastric emptying and precipitating
nausea and vomiting. Progesterone levels peak during the first trimester of
pregnancy just when the incidence of nausea and vomiting peaks. Some
studies failed to demonstrate a significant difference in semm levels between
24.1 5 symptomatic and asymptomatic pregnant women .
Controlled studies showed that thyroid function abnomalities occur in
some patients with HG. Studies report that 40-73% of patients with HG have an
elevated free thyroxine, T4 A correlation between nausea and
vomiting severify, T4 elevation, and thyroid stimulating hormone decline has
been reported but other studies found no relation between thyroid function and
symptom severity2'. These thyroid function abnormalities are transient and
concurrent with HG and usually spontaneously resolre as pregnancy
progresses. The mechanism of the increase in thyroid hormone level is
unknown. Whether these thyroid function abnomalities represent true
hyperthyroidism versus a biochemical alteration associated with pregnancy has
been questioned because trîiodothyronine, T3, is not constantly elevatedJO.
Other hormones such as adrenocortical stimulating hormone, cortisol,
luteinizing hormone, follicle stimulating hormone, growth hormone, and prolactin
have not been shown to dÎffer between patients with NVP and those without?
2.3.2 Gastrointestinal Motility
During pregnancy, esophageal, gastric, and small bowel rnotility are
impaired as a result of smooth muscle relaxation fostered by increased levels of
female sex hormones. This dysmotility may contribute to NVP.
Hormonal changes are postulated to alter the lower esophageal
sphincter (LES) function causing an incompetent sphincter. This alteration rnay
contribute not only to heartburn, but also to NVP. Studies have postulated that
alterations in the serurn concentration of female sex hormones affect the LES.
LES pressure reportedly gradually decreased du ring pregnancy in more than
50% of women with heartburn3'. One study reported that resting LES
pressures were abnormally low during al1 3 trimesters. with a nadir reached at
36 weeks' gestation. accornpanied by heartbum3? LES pressure normalized
during the postpartum period. This study confirmed that LES pressure
decreases early in pregnancy but normalizes postpartum.
Schulze et al used fernale opossums as an animal model to analyze how
estrogens and progesterone affect esophageal smooth muscle function during
pregnancy33. This study demonstrated a significant decrease in LES pressure
in the opossums in a pseudo - pregnancy state. Fisher et al also confirmed that
female sex homones affect LES cornpetence in opossums34. They found that
178- estradiol, progesterone or the combination significantly decreased the
maximal LES pressure response ta gastrin. norepinephrine. and acetylcholine.
The combination of the female sex homiones produced the strongest inhibition.
A delay in gastric emptying during pregnancy may also be important in
NVP. Progesterone, a srnooth muscle relaxant, inhibits gastric ernptying in
early pregnancy when levels are highly e~evated*~. In late pregnancy, the large
gravid utenis contributes to the manifestations of upper GI symptoms by
mechanically compressing the stomach. Gastric emptying in pregnancy has
been indirectly measured using paracetarno~~~. Paracetamol is not absorbed
from the stornach but is quickly absorbed from the small intestine, thus several
blood levels is a useful indicator of gastric emptying rateJ5. Whitehead et al
found no significant delay in gastric emptying in any trimester.
It has been postulated that a disturbance in the gastric electrical rhythm
could cause dysmotility and N V P ~ ~ . Gastric motility is controlled by electrical
slow waves. The electrogastrogram (EGG) records by electrical sensors placed
on the abdominal wall, identiwing the activity and sequences of myoelectrical
activity along the stomach3!
Normally, gastric electrical waves propagate at 3 cycles per minute
(cpm) from the proximal body to the distal a n t r ~ m ~ ~ . Variations from this
frequency are called gastrÎc dysrhythmias and are subcategorized into
bradygastnas (~2cpm) and tachygastrias (>5cpm). Gastric dysrhythmias were
identified in 81 % of the pregnant women expenencing nausea and vomiting
including tachygastria (4 to 9 cprn waves) in 17 patients, bradygastria (1 to 2
cpm waves) in 5, and Rat line patterns in 4". Rieno et al found that pregnant
women wRh nausea and vomiting had more unstable EGG activity compared
with women after abortions or non-pregnant controls3'. The restoration of a
normal slow wave pattern after abortion correlated with nomalization of
estradiol and progesterone levels.
Alterations in GI transit time. especially in the small bowel, have also
been investigated as potentially contributing to NVP. Lawson et al found that
transit times in the second and third trimester were significantly prolonged when
compared with either the first trimester or postparturnJ8. The longest increase in
transit time was observed when serum progesterone levels increased from less
than 1 to 80 nglml, suggesting that prolonged GI transit in later pregnancy
stems from an increase in progesterone. Wald et al found that transit time was
significantly prolonged during the third trimester when progesterone and
estradiol levels were high cornpared with postpartum perbd in 60% of patients.
Out of these more than one third had heartbum3'. Neither of these studies
related the delays in transit time to NVP.
2.3.3 Lipid Metabolism
The frequent alterations in serum lipids and lipoproteins in pregnant
women with HG are speculated to be related to altered hepatic hormonal
metabolism during pregnancy. One study found an increase in free and total
cholesterol, triglycerides, and phospholipid levels in patients with HG compared
with non - vomiting pregnant patients and non - pregnant contro~s~~. In addition
during late pregnancy, the total lipid content in all fractions was higher in
women with prior emesis during early pregnancy compared with women without
prior emesis. These alterations support the belief that an increased sensitivity of
the liver to an altered hormonal milieu rnay contribute to HG.
2.3.4 Psychological Factors
Several investigators have attributed this syndrome to psychological
factors. Previously about 50% of obstetricians believed that NVP was
psychologically based4'. It was attributed to a conscious attempt to reject an
unwanted pregnancy. Symptoms ceased in eariy pregnancy when fetal
rnovement began owing to the inability to deny further the fetus existence4'.
Fitsgerald et al found that women with nausea and vomiting during the first
trimester of pregnancy had more un planned or undesired pregnancies. but this
observation has not been corroborated by others". They also found that
pregnant subjects with nausea and vomiting during the first and through the
third trimester when compared with asymptomatic pregnant women more
frequently had a negative assessment of their relationship with their mothers.
In contrast Wolkind et al proposed that a lack of syrnptoms in a pregnant
wornan signaled denial of the reality of the pregnancy4*. latrakis et al found a
correlation between NVP and an unsuitable diet with large and infrequent
meals, poor communication with husband, obstetrician or both. stress and
doubts and inadequate information about pregnan~y~~. While none of these
theodes has been proven, they have led to guilt and shame among these
women aiding to their depression. Even to this day, these misconceptions are
often a rationale for delaying pharrnacotherapy for women suffering from NVP.
2.3.5 Vitamin Bs Deficiency
Several reports have suggested that women with HG exhibit vitamin B6
deficiencyZ3. Gant et al proposed that a possible explanation is the increased
need for the CO-enzyme pyridoxal phosphate. due to an increase in protein
metabolism induced by pregnancy4f There are also small randomized
controlled trials that have shown efficacy in the treatment of NVP with vitamin
2.4 OUTCOME
Several studies suggest that NVP is a favorable prognostic factor, with a
decreased risk of r n i ~ c a r r i a ~ e s ~ ~ , stil~births~~. fetal mortalityt2. pre - term
d e ~ i v e r $ ~ * ~ ~ , iow birth weight"*", prenatal rnor ta l i t~~~ or growth retardation12.
No increased incidence of congenital malformations has been repotted in
children born to symptomatic worner~~~.
Tierson and CO - workers reported that fetal deaths occurred significantly
more frequentiy among women without syrnptoms during pregnancy (20%)
compared with those who had symptoms of nausea (1 0%) or vomiting (5%14'.
Among the live births. asymptomatic women delivered a larger proportion of low
birth weight infants (20%) compared with those with nausea (6%) or vomiting
(1 0%). partly as a result of a lower gestational age at birth in asymptomatic
mothers4'. Asymptomatic women also tended to deliver earlier (1 1 %) than their
counterparts with nausea (2%) or vomiting (5%). Sirnilarly, Brandes et al
showed that gravidas without nausea and vomiting in the first trimester have
higher abortion and perinatal mortality rates47. This study also confirmed a
higher incidence of low birth - weight infants and shorter gestation period in
women without NVP than in those with symptoms. Weigel's meta -analysis of
11 studies confirmed the decreased risk of prenatal mortality and miscamage
associated with early NVP". The decrease in fetal mortality was limited only to
the first 20 weeks of gestation.
Hyperemesis gravidamm was first recognized as a potential cause of
death from starvation in the 18' century6. Today, HG rarely causes death. It
was a significant cause of matemal death before 1940, however because of the
lack of understanding about the associated fluid, electrolyte, and rnetabolic
dis turban ce^^^. The outcome of HG is controversial. Most studies report no
subsequent adverse effects on fetal and materna1 rnorbidity and mortality.
However, patients who manifest continued weight loss and electrolyte
disturbances may be at risk for decreased neonatal birth weight, growth
retardation, and fetal anomalies if symptoms are not controlled and electrolyte
51.52 abnonnalities are not corrected .
2.5 THERAPY FOR NVP
The management of NVP, depending on severity ranges from
conservative dietary modifications in the rnildly symptomatic wornan to drug
therapy and total parenteral nutrition for those with severe intractable
syrnptcms. Therapeutic abortion is rare and !açt resort. considered only when
matemal life is threatened.
Evidence from small randomized placebo - controlled trials has shown
that al1 of the following are effective for treatment of varying degrees of NVP:
phenothiaziness3, antihistamine H l b~ockers~~. Bendectin (doxylamine,
pyridoxine I d i ~ ~ c l o m i n e ) ~ ~ , pyridoxine P6 acupress~re~~. G inger is
often used for the treatment of nausea and vomiting however its efkacy has
yet to be establisheds6. Case series have variably suggested that
cor t ic~stero ids~~*~~. prokinetic agents5' and ondansetron6' may have therapeutic
roles to play although their fetal safety has not been established.
Metoclopromide has not been extensively studied for treatment of NVP,
eventhough in many countries it is commonly used in clinical practice6'. No
evidence - based formal guidelines exist for the management of NVP. In the
afterrnath of the thalidomide disaster, most anti - emetics are labeled as
contraindicated in pregnancy, despite evidence of safety in hurnan pregnancy.
Quality of Life has becorne a relevant measure of effkacy in clinical
trials6'. This results from a recognition of the limitations of available therapies
and a clearer view of the goals of treatment in patients whose diseases have a
grea! impact on daily ~ i f e ~ ~ . Quality of life c m be defined as an attempt to
quantify. in scientifically analyzable ternis, the net consequence of a disease
and its treatment on the patient's perception of hislher ability to live a useful and
fulfilling life6*. The overall concept of quality of life consists of a number of
distinct domains ranging from physical and emotional to social and economic
depending on what one wants to measure. Its use is spreading and its
importance is growing as a valid indicator of whether or not a medical treatment
is beneficia16'. Quality of Life trials can help improve the quality of the patients'
treatment and outcornes by addressing issues that are specific to specific
diseases.
The outcome measures in NVP clinical trials have traditionally been
duration of nausea and episodes of vomiting andior r e t ~ h i n g ~ ~ * ~ * ~ ~ ? In the
context of measuring physical symptoms, there are tools that will rneasure
nausea and vomiting in the settings of canceai68*69 and gastrointestinal
p r o b ~ e m s ~ ~ * ~ ~ , however there is no tool in the wntext of pregnancy. One such
instrument, the Rhodes lnventory - Fonn z6', has been used to measure
physical symptorns of NVP'~ but this tool does not provide a detailed picture of
the patient's subjective function including emotional and social problems that
are associated with NVP. The need to evaluate subjective morbidity is
imperative to assess the impact of both intervention and diseases on a patient's
~i festy le~~.
While a number of quality of life instruments exist for the general
population, they are unlikely to detect small clinically important changes and
rnay not focus adequately on the specific problems of NVP patients. The
problem with a genen'c instrument like the SF - 36 is its generalizability to
different populations. It asks general questions that either a population with
NVP, a population with asthma or a population with irritable bowel syndrome
can answer. However different illnesses may affect different bodily functions
and lead to different physical, emotional, social and occupational problems. As
a result a generic quality of life instrument may miss specific problematic issues
to specific populations. For instance women with NVP have reported feelings of
depression, consideration of termination of pregnancy, adverse effects on their
relationship with their partner. an adverse effect on their partner's daily life, lack
of support by their partner and feeling that NVP would be likely to ham their
f e t ~ s ' ~ * ~ ~ . The SF - 36 would not be able to detect these problems on NVP
patients. Another aspect of this condition is the treatment itself. Anti -
histamines can often cause drowsiness and sleepiness furthet debilitating
women from working inside or outside the home. A disease - specific measure
would have a narrow range of applicability and would attend to unique concems
that NVP women have. In doing so, overall benefit of a given intervention and
the impact of the disease on health status can be better assessed when such
specific problems are identified.
In other areas, this potential problem of general instruments has led
investigators to construct disease - specific questionnaires which have proven
7550 to be reliable to specific populations .
Guyatt et al developed a HRQL instrument for adult patients with irritable
bowel disease to assess psychosocial intervention to improve the quality of life
of these patients79. There were 5 domains of importance identified by these
patients and these included social, emotional, functional, bowel and systemic
dysfunctions. While a generic tool may address the emotional and social
aspects of this disease, it will not address the bowel dysfunction and patients
were reporting specific problems such 'avoiding events with no toilet', to this
disease.
Guyatt et al also developed a measure of health status for clinical trials in
heart failure. They identified areas of dysfunction such as dyspnea, fatigue,
sleep disturbance, social and cognitive dysfunction that are not addressed
properly on generic quality of life measures". By identifying the right problems.
they were able to advocate the use of such an instrument in other clinical trials
of patients with heart failure.
The outcome measures in cancer clinical trials have traditionally been
tumor response, freedom from disease and survival. However the need to
measure quality of life as an outcome measure in cancer trials has been
strongly advocated7*. Levine et al developed a questionnaire for use as an
outcome measure in clinical trials of adjuvant chemotherapy in wornen with
stage II breast cancer78. This instrument was intended to describe the morbidity
experienced by patients receiving chemotherapy and to measure its impact on
physical, emotional and social function. Chemotherapy can be very toxic and
evaluation of treatment is required to assess its overall benefit78. Cosmetic
problems such as loss of hair. were often reported and considered important by
this specific population.
Such studies confirrn the need for disease - specific instruments and the
need to identiw unique problems faced by different populations. An NVP -
specific instrument can better assess treatment and quality of life of NVP
patients by addressing NVP problems.
2.7 IMPACT OF NVP ON WOMEN'S LlVES
The severity of NVP has been measured by the degree of physical
symptoms8'. There has been very little study of the impact of NVP on other
aspects of patients' Iives, such as emotional well - being or function within the
home or outside the home. However, there is some evidence to suggest that
the NVP is associated with adverse effects on social and occupational
fu nction8'.
During the last decade, more attention has been focused on the
emotional distress associated with NVP, acknowledging that the psychological
morbidity in this condition is important in defining the quality of life of the
expectant mother and her f a m i ~ y ~ ~ ~ ' ~ . There are several epidemiological studies
that have investigated the magnitude of problems that NVP impose on the
4.5.81 lifestyle of pregnant women and their families .
O'Brien et al documented that. among a cohort of 147 pregnant women
with NVP (who booked with one of three obstetric or midwifery practices), 41
(29%) women experienced symptorns severe enough to oblige them to alter
their daily activities. Among a subset of 27 patients who were interviewed in
detail, effects on family. social, and/or occupational function were reported by
al1 women, regardless of whether their physical symptorns were mild (n=14
su bjects), moderate (n=9) or severe (n=518'.
Two other reports have described changes in occupational function (both
inside and outside the home) associated with NVP. One population-based
cohort study which enrolled 363 women with NVP, documented that 35% of
57% of women who worked outside the home spent a mean of 62 hours away
from paid work4. Based on the population of England and Wales and their
incidence of live births, these figures represent 8.6 million hours lost per year of
paid employment. This same study also found that 26% of women reported
time lost from housework.
Another cohort study (of consecutively booking antenatal patients)
identified 500 women with NVP, and documented that 25% of 64% who worked
outside the home reported time off paid work5. In addition, 25% of the 500
patients reported a mean of 8 hours lost from household tasks. These reports
emphasize the importance of NVP from a societal perspective, given that over
half of women now work outside the home and work inside the home entaiIs
care of young children and older farnily members.
2.8 SUMMARY
NVP is a poorly understood disorder and one for which many physicians
have little sympathy, perhaps because it is difficult to understand its
pathogenesis and to treat it. It may be associated with dysfunction in a variety
of different organs and many theories. including psychological andior behavioral
abnormalities, have been proposed to explain this syndrome but no single
theory provides an adequate explanation for it. Given the prevalence of NVP
and preliminary evidence of its impact on the occupational function and other
HRQL of women, rigorous evaluation of therapeutic interventions for NVP is in
the best interests of both women with NVP and society at large. A HRQL
instrument will heip the medical community to properly evaluate therapeutic
intewentions for NVP.
Section 3 METHODS
The NVP Quality of Life Questionnaire was developed using published
guidelines with proven reliability and validitya2.
3.1 ITEM-GENERATION
A list of items likely to be important to patients with NVP was generated
based on the following principles: physical, emotional and
social/dornestic/occupational health should be measured; items chosen must be
important to patients; the questionnaire should be responsive to changes in
symptoms of NVP in individuals over tirne; the questionnaire must be capable of
being completed by interview or by self - administration; and the questionnaire
should be short, given time and cost constraints.
3.2 SOURCES OF INFORMATION
Three sources of information were used. Firstly, women suffering frorn
NVP were consulted through a focus group conducted by the manufacturers of
~iclectin? The objective of this was to better understand the morbidity caused
by NVP. The video recording of this focus group was reviewed for items of
potential interests. The majority of items on the Item Reduction Questionnaire
were obtained from this recording. Secondly, a literature search was performed
on MEDLINE from 1966 to October 1996, using the following key words:
nausea, vomiting, pregnancy, pregnancy complications, disability evaluation,
and quality of life. Al1 potentially relevant articles were retrieved and reviewed.
Also reviewed were: i) genenc measures of quality of life (SF-36, the
Sickness Impact Profile. the Nottingham Health - Profile. the Self-administered
Health Status Questionnaire (Mark II and III), the McMaster Health Utilities
Index Questionnaire (Mark l Il). and the Rotterdam Symptoms Checklist); ii)
reports that described quality of life in the setting of nausea and vomiting 67,68.69. ,
iii) measures of upper gastrointestinal s y m p t o r n ~ ~ ~ ~ ~ ' and measures of vomiting
after emetogenic cancer ~ h e r n o t h e r a p y ~ ' ~ ~ ~ ~ ~ ~ ( FLIC (Functional Living Index:
Cancer) and the EORTC Core Quality of Life Questionnaire); iv) profiles of
nausea andlor v ~ r n i t i n g ~ ~ * ~ ~ * ~ ~ ; V) anrj scales of emotional well being (Hospital
Anxiety and Depression Scale, Beck Inventory, EPDS (Edinburgh Postnatal
Depression Scale), the Hamilton Rating Scale for Depression, the Profile of
Moods, and the CES - D (Center for Epidemiological Studies - Depression
Scale)). From this survey, relevant questions pertaining to nausea and
vomiting and emotional health were reviewed.
Most of the questions on the Item Reduction Questionnaire were
obtained from the NVP sufferers themselves. Other sources were used to
verify that these items were important to the women and to organize these
questions in a proper questionnaire format.
Thirdly, health professionals, two academic obstetricians, an academic
psychiatn'c women's health expert. three academic obstetnc nurses, and eleven
counselors from the Motherisk Program (a Teratology Information Sewice at the
Hospital for Sick Children) who provide counseling to pregnant women
interested in taking anti - emetic or other medication, were asked to review a
preliminary list of potentiai items for inclusion in the ltem Reduction
Questionnaire and were asked to provide additional useful items andlor
clarification of existing items.
The list of generated items was reviewed for duplication, and
redundancies were eliminated. 195 items were categorized into four domains by
the area of dysfunction which they appeared to address (i.e., physical
symptoms, environmental stimuli that aggravate or alleviate symptoms,
emotional function, and social/dornestic/occupational function). The ltem
Reduction Questionnaire is show in Appendix A. For the purposes of
developing a questionnaire where we can measure change in symptoms as an
index of improvement on quality of life. the category of environmental stimuli
that alleviate symptoms was excluded from the analysis since it would not
provide any information on improvement of symptoms in an intervention clinical
trial. The sole purpose of this category was to identify items whether it be
dietary or related to lifestyle that can be used in counseling to improve the
health status of patients with NVP through optimization of nutrition and changes
in daily activities.
3.3 ITEM REDUCTION
From March 1996 to July 1999, paid announcements on radio programs
and in Canadian and Arnerican women's magazines and newspapers have
advertised the Motherisk's interest in hearing from women with NVP, through a
1 - 800 nurnber to the NVP Healthline at the Hospital for Sick Children.
Women were eligible if they were:
1. Currently pregnant,
2. Gestationai age < 20 weeks, and had
3. Nausea, vomiting, or retching more than once, over the past week.
Women were excluded if they had:
1. Diarrhea which would suggest a Ru-like illness rather than NVP,
2. Severe NVP that would preclude telephone interview,
3. lnadequate cognitive skills knowledge of English to enable telephone
interview, and
3. Illness(es) (other than NVP) known or suspected to affect quality of life (e.g.,
asthma, autoimmune disease like systemic lupus erythernatosus).
3.4 STUDY PROCEDURES
Eligible callen were asked for their permission to undergo a detailed, 30
- 40 minute telephone intenriew (Appendix A). McMaster University guidelines
for conduct of telephone interview were followed shown in Appendix B.
Baseline information was collected about matemal demographics,
medical and obstetric histories, as well as exposure to other medications,
chemicals, cigarettes and/or recreational alcohol or drugs. It was not necessary
to have had ultrasonographic dating or diagnosis of multiple gestation (which
was ascertained at telephone follow - up at 20 weeks gestation). Women
described the severity of their NVP, duration of daily nausea, frequency of
vomiting/retching, and current anti-emetic therapy (druglnon-dnig). The Item
Reduction Questionnaire (Appendix A) was then administered by experienced
counselors who asked women if any of the 195 items had been a problern for
them over the past week. For items in which women indicated that they
experienced a problem, they were asked to rate the importance of the item
using a five - point Likert scale (from "very importantn to "not at al1 important")
shown in Appendix C. The response options were the same for al1 questions.
Therefore. the caller was asked to record the response options on a piece of
paper which she kept in front of her for reference throughout the interview. The
accuracy of what the caller recorded was checked by asking her to dictate back
to the interviewer what she had written for the first few questions in each
section.
After the initial interview. the caller was asked for her pemission to be
contacted at approximately 20 weeks gestation for a second telephone
interview to further characterize symptoms (and their resolutionlpersistence),
confirm the diagnosis of NVP and to ascertain the prevalence of multiple
gestation.
For each item of each domain. the frequency (Le.. proportion of
individuals who identify that item as problematic) and mean importance (Le.,
mean importance score of al1 individuals who regard that item as problematic)
were multiplied to get the "overall impactn of that item.
Patterns of responses (by rank ordering of items by overall impact and
comprising mean overall impact scores by Analysis of Variance) were exarnined
with respect to the following patient characteristics: a) severity of NVP (based
on self-classification, duration of daily nausea and frequency of vomiting), b)
ingestion of anti - emetic drug therapy (none, one, or two or more anti -
emetics), c) use of non - phamacological remedies for NVP (none, one or
more), e.g., acupressureiacupuncture, coining, and d) demographic
characteristics which have been associated with NVP" (i.e. age (~25, 26-35,
and >35), parity (primigravida (first pregnancy, G = 1) or rnultigravida (G > l)),
smoking (curent nonsmoker and smoker), education level (i.e. public school,
hig h school, college/university. or post-graduate) and occupation (Le.
homemaker, student, part - time and full - time worker)). These analyses were
done to investigate if there was any relationship between these factors and the
pattern of responses. so as to consider deriving different questionnaires for
evaluation of treatment among different groups of patients.
To explore the relationship between items. to gain insight into the validity
of the four domains chosen on the basis of clinical sensibility, and to reduce the
number of items in each domain. a factor analysis was conducted. A principal
component analysis was done and a scree plot was viewed to decide on the
appropriate number of factors retained. Varimax rotations were done for al1
solutions that seemed credible on the basis of the scree plot.
3.6 ITEM PRESENTATION
The 30 items with the highest "overall impact" were retained for the final
questionnaire and were organized into the following domains: physical
syrnptoms and their triggers, fatigue, emotional health and
social/domestic/occupational limitations. Questions were stated as
unambiguously as possible and asked patients about symptoms over the
previous week. given the variable duration of NVP. Close-ended questions with
seven - point likert scale response options were used.
3.7 SAMPLE SlZE
Without subgroup analyses, the item reduction questionnaire could be
administered to 100 patients, to give the narrowest confidence interval of t 10%
(Le., the confidence interval around a proportion is widest when that proportion
is 50%. A sarnple size of 100 gives a CI around 50% of [40%. 60°h] in 95% of
situations). However, given the nurnber of su bgroup analyses (i.e., 1 O), the
proposed sarnple size was measured to 500.
The item Reduction Questionnaire was approved by the Hospital for Sick
Children's Research Ethics Board as were the general clinical activities of the
NVP Healthline.
Section 4 RESULTS
4.1 RECRUITMENT FOR THE ITEM REDUCTION PHASE
Of 1853 women who called the NVP Healthline between February 1996
and July 1 999. 542 patients completed the questionnaire. The recruitrnent
charts are shown in figure 1. There is no pattern for recruitment among the 3
years. Wornen were recniited depending on the number of calls received each
rnonth on the NVP Healthline.
Figure 1: Recruitment Charts of 500 wornen between 1997 and 1999
- - - ----. .- ---
1997 Recruitment Chart
Figure 1: Recruitrnent Charts of 500 wornen between 1997 and 1999 (cont'd)
1998 Recruitrnent Chart
- - - .
1999 Recruitment Chart
We reviewed ail 542 filled forms and 42 women were excluded because
they had not fit the inclusion criteria to begin with but filled out a form anyways.
The reasons for exclusions were due to depression (5). had the Ru and were on
antibiotics (4). had other medical conditions (9). were too sick to continue the
questionnaire (2) and did not understand the form or completed the form
incorrect1 y (22).
The remaining 131 1 women who were approached to participate in the
study were not interviewed because they did not fit the inclusion criteria (644) or
did not want to fiIl out the questionnaire (667). Most of the women were
excluded due to medical conditions such as blood pressure problems (57), liver
disease (4), kidney disease (7), gastrointestinal problems (85). diabetes (1 5).
heart disease (1 9), psychiatric disorders (18), central nemous system problems
(8). respiratory (97) , depression (63) and migraines (52). Other reasons for
exclusion were the fact that some wornen did not speak proper English (8),
some wornen were greater than 20 weeks gestational age (1 09). some women
were planning and wanted information (14) and others were excluded for other
reasons not mentioned (88).
4.2 MATERNAL DEMOGRAPHICS
The characteristics of the 500 participants are summarized in table 1.
batients -values are numbers of patients tnless stated otherwise
l~ab le I : Matemal Characteristics of 500
Mean Matemal Age (SD)
Missing
Marital S tatus
Gravida
Birth Oefects
Smoking
Alcohol
Crack
Cocaine
Marijuana
Caucasian BIack rrn r v # d C d
Asian Latin American Native Amencan Missing
Single MameWith partner Separated'Divorced Ulidowed Missing
Primigra vide Multigravida Missing Mean G (SD) Mean P (SD) Mean SA (SD) Mesn TA (SD) Yes No Missing
Yes No Missing Yes No Missing
Yes No Missing Yes No Missing Yes No Missing
$0 =standard deviation; G = gravidity; P = parity;
31 .O5 (4.50) years 2
9.45 (2.61 ) weeks
4 = spontaneous abartion:
latients -values are numbers of patients inless stated otherwise (cont'd)
l~able I : Matemal Charactefistics of 500
Medical Kidney History
Hypertension
Respiratory
Epilepsy
Other
Vitamin Supplements
Education Public School High School CollegeNniversity Post-Graduate Missing
Occupation Homemaker Full-Tirne worker Student Part-77me worker Missing
Yes no missing
Y= no
missing
Yes no
missing
Y= no missing
Yes no missing
Yes no Missing
Y= no missing
Yes no missing
Yes no missing
Y= mild NVP modemte sevem
no mild W P moderate sevem
missing
iatients - vatues are numbers of patients intess stated otherwise (cont'd)
iable 1 : Matemal Characterfstics of 500
NVP
Duration Of Nausea
Vomiting Frequency
Anti- Emetics
Non-drugs
Mild Moderate Severe Missing
Rarely or never Some of the time Most of the tirne Always Missing
Rarely or never Some of the time Most of the lime Always Missing
Missing Diclectin Gravor Vitamin b6 Phenergan Maxeran Compazine Zofran Others
O
1
> 7
Missing Herbal remedies Acupuncture/acupressure Massage therapy Hypnosis Coining Others
The women were on average 30 years of age, Caucasian, and had been
pregnant before. They mostly enrolled at less than 10 weeks gestational age.
Most women had a collegeluniversity degree and rnost held a full time job with
a wide range of professions ranging from teaching, medicine, pharmacy,
chartered accounting, nursing, child-caring, professorship, selfernployed
businesses, secretarial, waitressing and technicians jobs. Alrnost 75% of the
women were taking vitamin supplements. Most women who were taking
vitamin supplernents were on the moderate part of the NVP spectrum while
women who were not. had mostly severe NVP. Two women smoked marijuana
to alleviate their NVP symptoms, but there were no reports on cocaine or crack
abuse. No other elicit drug usage was reported either. About 3% of the women
smoked cigarettes and 2% drank alcohol at the time of the interview. There
were no outstanding medical histones among the women in this cohort since
they were excluded frorn the rectuitment. The most commonly reported
medical conditions were thyroid and respiratory problems such as
hypothyroidism and asthma respectively. Most women tended to be on the
severe end of the NVP spectrum with constant nausea and vomiting most of the
tirne. The majority of women did not take anti - emetics or alternative
medications to alleviate their symptoms. Of those who took medications, most
were taking ~iclectin" and of those who used non - dnig alternatives,
acupressure was mostly reported.
4.3 OVERALL IMPACT SCORES
The highest scoring items with overall impact scores greater than or
equal to 2 are presented in table II. There were 66 items out of the original 195
items.
f ~ab le II : r 2.0 scoring items of the f 95 items presented to patients with NVP
Symp tom
Physical symptoms Nausea Feeling sfck to your stomach Fatigue Lack of energy Feeling wom out Tiredness Poor appetite Exhaustion Vomiting Bad taste in your mouth Dry-heaves Sleeping or napping for most of the day Not carfng for younelf as you usually do Burping or belching Sleeping pooriy Sitting for most of the day Excessive thirst
Environmental stimuli Been exposed to certain smells Not eaten for longer than you would like ln the evening In the morning Had certain foods In the aftemoon Been in a hot or stuffy room With movement Bmshing your teeth
1 proportion of patients reporting item as troubleson
Frequency Proportion Mean Overall Importanceu impactm
(maximum = 1 .O) ** mean importance score in subjeds who reported item as troublesome (maximum = 5.0) "overall impact = proportion ' mean importance (maximum = 5.0)
Table II : r 2.0 scoring items of the 195 itemÏpresented to patients with NVP (cont'd)
Syrnp tom
Emotional function Fed up with being sick Frustrated Reassured that your symptoms are part of normal pregnancy
Less interested in sex l Everything is an effort Emotional Feeling downheaned and biue
Worried about your heaith Can't enjoy your pregnancy Afraid that you "II vomit without warning or in publlc Irritable
: Moody Grouchy
Feeling that the days seem to drag Worried about having nauseahrorniting in a future pregnancy Worrfed that your medications may hann your baby Feeling sad, unhappy Less concemed about your physical appearance than usual In good spirits, happy Guilty about not spending as rnuch time with your famiiy Guilty about not spending as much urne with your partner Feeling depressed, gloorny Feeling overwhelmed Tearful
SociaUdornestidoccupational function Difficulty preparing or cooking meals Accomplished less than you would Ilke Took longer to get things done than usual kelying on your partner to do things you would nomally do for your famfly Took extra effort to perform worklother activitfes 'Difficulty perforrning workiother activities DifFiculty maintaining your normal social activlties with famiIy, friends, neighbors, or social groups Limited in the kind of worWactiviffes you have been able to do Difficulty tooking after the home Cut down on the amount of time you spent at work or other activities Partner thinks this is part of normal pregnancy Dlfficulty shopping for food Difficult deaning the bathrwm Difficuity maintaining interests and hobbies (like sports, arts and crafts) DifFiculty sming wfth your family dunng meals Your partner feeling helpless, unable to help you
*proportjon of patients reporting item as troublesome (maximum = 1; item troublesome (maximum impact
Frequency Proportion* Mean Ovemll Importance* Impact-
; " mean importance score in subie& who importance (maximum
The highest scores were seen in the physical and emotional categories
suggesting that physical symptoms may lead to emotionai distress or that
emotional distress rnay be an independent aspect of NVP.
For al1 domains there were very little differences in the order of overall
impact of the 10 highest ranking items by the 10 subgroups as shown in
table III. The problems related to NVP were reported by the participating
women irrespective of age, parity. smoking. occupation, education. NVP
severity, nausea duration, episodes of vomiting, and anti - emetic therapy
(either drug or non - drug) suggesting that one questionnaire is applicable to al1
segments of the population examined in this study. Occasionally in certain
segments of the population, certain items were not relatively, equally ranked
amongst the subgroups because the number of women differed in those
subgroups. For instance, smokers versus non - smokers reported similar items
but there were differences because the sample size of smokers (14) was much
smaller than the sample size of non - smokers (485). However overall the
women reported the same items.
Ph yslcal Syrnptoms
nausea feeling sick to your stomach
fatigue lack of energy feeling wom out tiredness poor appetite exhaustion vomlting bad faste in your mouth
ITable III : Oder of ovenll importance of items by subgroup* .
Environmental Sffmull
been exposed to certaln smelb not eaten for longer than you would like in the evenfng in the morning had wftain foods in the aftemoon been In a hot or stuffy room with movement brushing your teeth you've changed position (like standing up from sitting)
Emoffonal Fun Won
SociaU Domeslid
Occupational Functfon
fed up with being sick fntstrated reassured that your symptoms are part of normal pregnancy
less interested in sex everything fs an effort emotfonal feeling downhearted and blue worried about your heaith feeling that your are punished afraid that you will vomit without waming or In public
difficulty prepafing or cooking meals accomplished less than you would like took longer to get things done than usual mlying on your partner to do thfngs you would normally do foi your family took extra effort to perfom woWother activities difficulty perfonning woriciother activities difficulty maintainhg your normal social acüvitks wlth family, ftiends, neighbors, or sociai groups limited in the kind of worWadfvfties you have been able to do
difficulty looking after the home cut down on the amount of time you spent at work or other activities
I
'Order in which mtients identffied items as being important by subqmups - for example w m n > 35 years of ac - JE
identified 'naus& as the mast important symptom and feeling si&-to your stomach & second; women c 25 years of age identified 'si& to your stomadi' as the m a t important and nausea as second. ûverall importanœ = proportion mean importance: see table Il. Only top 10 items are Iisted.
able III : Order of overall importance of items by subgroup* (cont'd) 1
Ph ysical Symptoms
EnvÏmnmental Stimuli
SociaV DomesW
Occupational hrnction
Nausea feeling sic)< to your stomach Fatigue lack of energy feeling worn out nredness poor appetite Exhaustian Vomiting bad taste in yout mouth
been exposed to certain smells not eaten for longer than you would like in the evening in the momlng had certain foods in the afternoon been in a hot or stuffy room with movement brushing your teeth you've changed position (like standing up from sitting)
fed up with being sick Fnistrated reassured that your syrnptoms are part of normal pregnancy less interested in sex everything is an effort emotfonal feeling downhearted and blua worried about your health feeling that your are punished afraid that you will vomit wfthout warning or in public
difficulty preparlng or cooking rneals Accomplished less than you would like took longer to get things done than usuat relying on your partner to do things you would normally do for your farnily took extra effort to perform workfother activitles diificulty perfonning worklother acthrities difficulty maintainhg your normal soda1 activities wfth farntly, friends, neighbors, or social groups ltmited ln the kind o f wofklactivities you have been able to do difficulîy looking after the home cut d o m on the amount of Ume you spent at work or other activities
Overail importance = proportion ' mean importance: see table I t. Oniy top 10 items are
rable Ill : Order of overall importance of items by subgroup' (confd)
Environmental Stimuli
SociaU Domestic/
Occupational Fundion
Nausea feeling sick to your stomach Fatigue lack of energy feeling wom out Tiredness poor appetite Exhaustion VomitMg bad taste in your mouth
been exposed to certain smells not eaten for longer than you would like in the evening in the rnorning had certain foods in the aftemoon been In a hot or stuffy room with movement brushing your teeth you've changed position (like standing up frorn sitting)
fed up with being sfck Frustrateci reassured that your symptoms are part of normal pregnancy less interested in sex everything is an effort emotional feeling downhearted and blue worried about your health feeling that your are punished afraid that you will vomit without waming or in public
difnculty preparing or cooklng meals Accomplished l e s than you would like took longer to get things done than usual relying on your parlier to do things you would normally do for your family took extra effort to perfom worWother activities difficulty perfomifng worklother activiti es difficulty maintalning your normal social: activltles with family, friands, neighbors, or social groups limited in the kind of worklactivities you have been able to do difficolty looking after the home cut down on the amount of tirne you spent at work or other activitfes
' Overall importance = proportion ' mean importance: see table Il. Onty top 10 items are I
Smoking
Yes 2 1
6 4
3 5 1 O
9 a 13
2 7 3 6 5 4 12 9
10
8
3 7 6 5 1 O 4
14
29 15
8
8 3 9 14
4 1 13
7 6
1 O
l ~ab l e III : Order of overall importance of items by subgroup* (cont'd) 1
P hysical Symptams
Environmental Stimuli
Emo tional
Function
SociaV Dornestïcî
Occupational Funclion
Nausea feeling sick to your stomach Fatigue lack of energy feeling wom out tiredness poor appetite exhaustion vomiting bad taste in your mouth
been exposed to certain smells not eaten for longer than you would like in the evening in the rnoming had certain foods in the afternoon been in a hot or stuffy room with movement brushing your teeth you've changed position (like standing up from sitting)
fed up with being sick
frustrated reassured that your symptoms are part of normal pregnancy less interested in sex everything is an effort emotional feeling downhearted and blue worried about your health feeling that your are punished afraid that you will vomit without wamfng or in public
diffïculty preparing or cooking meals accomplished less than you would llke took longer to get things done than usuai relying on your partner to do things you would nomalIy do for your family took extra effort to perform worklother activities difficulty performing worklother activities difficulty maintaining your normal social activities with farnily, Mends, neighbors or social groups limfted in the kind of worklactfviües you have been able to do dfffïculty looking atter the home cut down on the amount of time you spent at work or other activities
Overall importance = proportion ' rnean importance: see table Il. Only top 10 items are I " Public &ho01 catGoi$ was omhed fmm this anafysis because its iample size was ta
Educationn highschool
1
2 5 3 6 4
8 9
7 10
1
2 3 5 4
6 7 9 8 1 O
1
2 6 4
7 3 1 O 5 8 12
1
3 4
2
6 5 8
7 9 13
collegeluni- post-
isted. o small(6); See table 1.
'able Ill : Order of overall importance of items by subgroup' (cont'd)
Ph ysical Symptoms
Envlmnmental S ffmuii
Emoffonal Functlon
nausea feeling sick to yout stomach fatigue lack of energy feeling worn out tiredness poor appetite exhaustion
vomiting bad taste in your mouth
been exposed to certain smells not eaten for longer than you would Iike in the evening in the rnoming had certain foods in the aftemoon been in a hot or stuffy room with rnovement brushing your teeth you've changed position (Iike standing up from sitting)
fed up with being sick frustrated reassured that your symptorns are part of normal pmgnancy less intarested in sex everything is an effort emotional feeling downhearted and blue worried about your health feeling that your are punished afraid that you will vomit without waming or in public
difficulty preparing or cooking meals accomplished less than you would like took longer to get things done than usual relyfng on your partner l o do things you would nomally do for your family took extra effort to perform worWother activities difficulty perfonning worldother actMtfes difficulty maintafning your normal social activities with family, Mends, neighbors or social groups limited in the kind of worWactivities you have been able to do difficulty looking aiter the home cut down on the amount of time you spent at worlc or other activities
Overall importance = proportion ' mean importance: see table Il. Onk t o ~ 10 items are " tud dent ktegory was omitted frorn this aialysis because its sampleiiré was too sma
3ccupation" homemaker
ited. 8); See table 1,
rable Ill : Order of overall importance of items by subgroup* (cont'd) 1
Physical Symp toms
Envimnmental Stimuli
Ernoffonal Function
SociaV Domesüci
Occupational Function
nausea feeling sick to your stomach fatigue lack of energy feeling worn out tiredness poor appetite exhaustion vomiting bad taste in your mouth
been exposed to certain smells not eaten for longer than you would like in the evening in the morning had certain foods in the aftemoon been in a hot or stuffy room with movement brushing your teeth you've changed position (like standing up from sitting)
fed up with being sick frustrated reassured that your symptorns are part of normal pregnancy less interested ln sex everything is an effort emotional feeling downhearted and blue worrfed about your health feeling mat your are punished afraid that you will vomit wlthout warning or in public
difficulty preparing or woking meals accomplished less than you would like took longer to get things done than usual relying on your partner to do thlngs you would normally do for your family took extra effort to petform worklother acthrities difficulty perfonning worWother activities difficulty rnaintaining your nomal social activities with family, friends, neighbon or social groups limited in the kind of worWactivities you have been able to do difficulty looking after the home cut down on the amount of üme you spent at work or other activities
Overall importance = propoRion ' rnean importance: see table Il. Only top 10 items are
YVP Severity mild
3 6 1
2 5 4
8 7
14
10
severe 1
2 3 4
6 5
8
9
7
12
1
2 3 5 4
6 7
8 9
10
1
2
10
5 3
6 4
8 7 9
1
2 3 4
5 6 8
9 7
10
able III : Order of overall importance of items by subgroup' (cont'd)
Ph ysical Symptoms
Envimnmental Stimuli
Emotional Funcffon
SociaU Oomesllc/
Occupaffonal Funcffon
nausea feeling sick to your stomach fatigue lack of energy feeling wom out tiredness poor appettite exhaustion vorniting bad taste in your rnouth
been exposed to certain smells not eaten for longer than you would like in the evening in the rnorning had certain foods in the afternoon been in a hot or s tuw room with movement brushing your teeth you've changed position (like standing up frorn sittlng)
fed up with being sick frustrated reassured that your symptoms are part of normal pregnancy less interested in sex everything is an effort emotional feeling downhearted and blue worried about your health feeling that your are punished afraid that you wîll vomit without warning or in public
difficulty prepaffng or woking meals accomplished less than your would like took longet to get things done than usual relying on your partnet to do things you would nonnally do for your family took extra effort to perform workiother activities difficulty performing worklother adivities difficulty maintaining your normal social activitles wfth farnily, friends, neighbors or social gtoups llmited in the kind of worklactivities you have bem able to do difficulty looktng after the home cut down on the amount of Ume you spent at work or other acüvities
Overall importance = proportion * mean importance: see table II. Onty top 10 items are was this sample site was
most of th8 tjm8
1
2
3 6 4
5 7 9
8
10
1
2
3 5 4
6
7 8
9
1 O
1
2 4
3 7
6 5 8 1 O 9
2 1 4
3
5
6
9
7 10
8
too
some of the tirne
1
6
2 3
4
5 10 7
8
15
3 2 1
4
7 6 5 10 8 13
4
8
3 7
16 13
18
9 15
6
1 4
3
5
6 10
8
11
7
12
I
l'
e
iB small (3); See table 1.
rable III : Order of overall importance of items by subgroupg (cont'd) t
Environmental Stimuli
Emo tional Function
SoclaU Domestfcî
Occupational Functfon
nausea feeling sick to your stomach fatigue lack of energy feeling wom out
tiredness poor appetite exhaustion vomiting bad taste in your mouth
been exposed to certain srnells not eaten for longer than you would like in the evening in the momjng had certain foods in the afternoon been in a hot or stuffy room with movement brushing your teeth you've changed position (like standing up frorn sitting)
fed up with being sick frustrated reassured that your symptoms are part of normal pregnancy less interestai in sex everything is an effort
emotfonal feeling downhearted and blue worried about your health feeling that your are punished afraid that you will vomit without warning or in public
difiiculty preparing or cooking rneals accomplished less than you would like took longer to get thinqs done than usual relying on your partnet to do things you would normally do for your farnily took extra effort to perfonn worlrlother activities difficuity performing worWother activities diffïculty maintainhg your normal social activities with farnily, friends, neighbors or social groups lfrnited in the kind of wotWactivities you have been able to do difliculty lwking after the home cut d o m on the amount of time you spemt at work or other activities
'Overall importance = proportion ' mean importance: çee table II. Onty top 10 items are I ed.
Table III : Order of overall importance of items by subgroup* (confd)
I
Physical nausea Symptoms feeling sick to your stomach
fatigue lack of energy feeling wom out tiredness poor appetite exhaustjon vomiting bad taste in your mouth
Environmental been exposed to certain smells Stimuli not eaten for longer than you would like
in the evening in the morning had certain foods in the afternoon been in a hot or s tuw room with movement brushing your teeth you've changed position (like standing up from sitting)
Emotional fed up with being sick Function frusttated
reassured that your symptoms are part of normal pregnancy less interested in sex everything is an effort emotional feeling downhearted and blue worried about your health feeling that your are punished afraid that you will vomit without mrning or in public
SoclaU difficulty preparing or cooking rneals DomesW accomplished less than you would like
Occupaffonal took longer to get things done than usual Function relying on your partner to do things you would norrrtally do for
your family took extra effort to perfom woriciother activities difficulty performing worWother activities difnculty maintaining your nomal social activities with fimily, friends, neighbors or social groups limited in the kind of worklactivltfes you have been abfe to do difficulty looking after the home cut d o m on the amount of Ume you spent at work or other activities
Anti-emetic Use O 1 >1
1 1 1
2 2 2 3 5 4
4 4 5
6 3 3
5 6 6 8 7 7 7 8 8 Y Y 12 10 11 14
I
' Overall importance = proportion ' mean importance: see table II, Oniy top 10 items are listed. 1
rable III : Order of overall importance of items by subgroupœ (cont'd)
Nondrug Use
Ph ysical Symptoms
Environmental Stimuli
Emotional Fundon
nausea feeling sick to your stornach fatigue lack of energy feeling worn out tiredness poor appetite exhaustion vomiting bad taste In your mouth
been exposed to certain smells not eaten for longer than you would like in the evening in the morning had certain foods in the afternoon been In a hot or stuffy room with movernent brushing your teeth you've changed position (like standing up from sitting)
fed up with being sick frusttated reassured that your syrnptoms are part of normal pregnancy less interested in sex everything is an effort emotional feeling downhearted and blue worried about your health feeling that your are punished afrajd that you will vomit without waming or in public
difficulty preparing or woking meals accomplished less than you would like took longer to get things done than usual relying on your partner to do things you would normalIy do for your family took extra effort to perfom woddother activities difficulty performing worklother actMties difficulty maintaining your normal social actlvitfes with family, friends, neighbors or social groups limited in the kind of worklactivities you have been able to do difficulty looking after the home cut down on the amount of tirne you spent at work or other activiff es
Overall imporéance = proportion ' mean importance: see table II. Only top 10 items are li
O
In contrast, table IV shows however that the mean overall impact scores
were higher in women whose self - assessrnent of NVP was severe, who
reported severe nausea or vomiting, or who used anti - emetic therapy,
particularly dnig therapy. The higher scores in women taking multiple drugs is
reflective of the NVP seventy indicating that it is an index for symptom severity.
Eventhough the scores tended to be higher in these subgroups of wornen, they
were still reporting the same items as problematic.
rable IV : Mean Overall Impact by Subgroup '
AI1 Items
Physical
Symptoms
Environmental Stimull
Parity pnmipamus multipamus P value"
'Scores by domain for 1
each of the subgroups of patients ( overall impact = propartion ' mean importance : see table 2). " Probability of difference within subgroup by analysis of variance.
Ph ysical Symptoms
Envfmnmental Stimuli
Emotlonal Function
SocfaU Domesffd
Occupational Function
Scores by domain for e
Smoking
YeS no P value"
l ~ a b l e N : Mean Overall Impact by Subgroup' (conïd) I
t
-L
1 of the subgroups of patients ( c
Education highschool college/uni- post- P valueu
versity graduate
erall impact = proportion ' mean importance : see table 2). " ~robabilh of difference within subgroup by anatysis of variance.
rable IV : Mean Overall Impact by Subgroup' (cont'd)
Physlcal Symptoms
Envfmnmental S ffmulf
SocCaU Domesffd
Occupaffonal Function
'romemaker full-time part-time P value" worker worker
Scores by domain for each of the subgmups of patients ( overall impact =
NVP Severity mild moderate severe P value"
9.60E-17
0.0006
0.006
4.41 5 1 0
3.39E-05
opartion ' mean importance : see table 2). " Probability of difference wittiin subgroup by analysis of variance.
ïable IV : Mean Overall lmpact by Subgroup* (cont'd)
Nauseo always most of the some of the P valuen
tirne lime
Vom iURetch
AI1 Items
Physical Symptoms
Envimnmenîal Stimuli
Emotional Function
SociaU Domestid
Occupational Fonction
'Scores by domain fc each of the subgroups of patients ( overall impa = proportion ' mean importance : see table-2). " Probability of difference within subgroup by analysis of variance.
able IV : Mean Overall Impact by Subgroup* (cont'd) 1 Anti-emetlc Use Nondnrg Use
O 1 P value"
4.69E-08
0.04
0.4
1.40E-05
0.004
AI1 ltems
Physical Symptoms
Envimnmenîal Stimuli
Emofional Function
SociaU Domesffd
Occupational Function
Scores by dornain for ! a d of the subgroups of patients ( overall npact = proportion ' mean importance : see table 2). * Probability of difference wiîhin subgroup by analysis of variance.
4.4 FACTOR ANALYSE
Appendix D shows the results of the factor analysis. Using al1 items with
an impact score of 2 2.0 resulted in 66 items. Our primary criterion for including
an item on the final questionnaire was the overall impact of that item on the
population. The cutoff d 2 2.0 was chosen hecause we wanted to include
items that were relatively important to the women and this allowed for a factor
analysis on 66 items out of 195 items of the questionnaire (Appendix A). But
we also wanted to reduce the number of items to be further analyzed hence we
excluded al1 items below the cutoff of 2.0 as they were rated to be "not at al1
important" by the women according to the five - point Likert Scale (Appendix C).
To identify the number of factors to retain we used a principal component
analysis. We considered al1 factors with eigenvalues > 1 .O and examined a
scree plot to determine how many factors to retain. Eigenvalues describe the
strength of the relationships between the items in each factor and is defined as
the amount of variance that is accounted for by each factor? The eigenvalue
rises as the proportion of variance explained by a factor increases and
investigators often use a cut of 1 .O to identify factors that warrant further
consideration. Scree plots are plots of the factors on the X - axis and the
eigenvalues dong the Y - axis. They present the eigenvalues of each factor in
descending order and helps determine where there is a rapid drop in the
proportion of variance explaineda6.
Sixteen factors had an eigenvalue > 1 .O, however the scree plot
indicated that an up to four factor model was optimal as shown in figure 2
(Appendix O). A one factor solution would defeat the purposes of the factor
analysis since we wanted to group the items into domains and a two factor
solution would group items that belonged to four different original domains
together, therefore a three or four factor solution seemed optimal.
After deciding on the number of factors, we used a varimax rotation to
determine the factor loadings and potential domains. The varimax rotation was
used to maximize the variance explained by each factor. Since an item can
either load on one or more factors or have positive or negative loadings, a
rotation of the loading values facilitated separation of factors with an optimal
balance of variance explained by each factor in order to interpret them easier.
If an item had a factor loading of 0.50 or greater they were associated with that
factor. If an item did not have a factor loading of at least 0.50 on any of the
factors, the items were not included within any factor. In this case the scree
plot suggested a model of up to four factors so we repeated the varimax
rotation examining three and four factor solutions and we chose the solution
that made the most intuitive sense. The four factor solution was the best
solution since it assigned items into one of four factors that captured the original
domains. It best represented items that have been reported by the NVP
patients as troublesome and it confirmed Our four original domains: physical
symptorns, ernotional function, environmental stimuli and
socialldomestic/occupational function. The summary of the grouping of items
into the four factor model is presented in table V.
Names for each dornain were chosen based on existing. expert
knowledge of NVP. Correlation matrices were drawn for the best factor
solution, the four factor model, to examine the correlations between the items in
each factor. If items had a correlation of greater than or equal to 0.65, they
were considered highly correlated and were addressed as one question.
Since Our primary criterion for including an item on the final questionnaire
was the impact of that item on the population, items that were rated important
by the women and had an overall impact score 2 3.0, but were absent from the
four factor solution, were still used on the final questionnaire and were placed in
their appropriate domains. A factor analysis was mainly used to guide
placement of items into HRQL domains and to reduce the number of items on
the final questionnaire. Certain items such as 'nausea', 'vomiting', and 'dry
heaves' were retained for face - validity. It's intuitive that a questionnaire on
NVP should address such items. They failed to anse from the factor analysis
because they were not highly associated with any of the factors in the solution,
however they had high impact scores therefore were retained on the final
questionnaire. To do such placements of high impact score items, we omitted
items from the factor analysis that had low impact scores in order to construct a
final questionnaire with 30 questions that addressed at least four items in each
domain.
- - - --- - - -
Table V : 4 factor solution using a varimax rotation for al1 66 items with impact score r 2.0 ---- ---- --------------------------- Factor 1 (SociaUDomestic/Occupational Limitations) everythjng is an effort cut down on the amount of tlme
spent at work or other activities accomplished less than you would like difficulty preparing rneals relying on your partner to do things you would
norrnally do for your family !ook longer to get Wngs done than usua! difficulty perforrnlng worWother activitiesu difficulty cleaning bathroom" took extra effort to perform worWother activitiesa lirnited in the kind of worWother activities you
have been able to doa difficulty looking after the home dlfficulty shopping for food difficulty sitting with your family durlng rneals" difficulty maintaining your normal social
activities with family, friends, nelghbors or social groups
difficulty rnaintaining interests and hobbies (llke sports, arts and crafts)"
Factor 2 (Emotional Health) feeling downhearted and blue feeling sad, unhappy" feeling depressed, gloomy* cant enjoy your pregnancy frustrated irritablep," g r o ~ c h ~ ~ . ~ moody p." emotional tearful* feeling ovemhelrned"
Factor 3 (Fatigue) fatigue worn outr lack of energyX exhaustion tiredness
Factor 4 (Physical Symptoms and their triggers) had certain foods exposed to certain smells
Factor Loadings*
Variance explained by each factor: factor 1.9.08331 51; factor 2.6.8324408; fidor 3. S.0174461; faclor 4.4.5744088- 'Al1 items presented have factor loadings 2 0.5 therefore assoaated with that factor. "Ornitted items due to low impact scores. %rns in Factor 1 mat have correlation coefficients >= 0.65 between each other. Pltems in Factor 2 that have correlation coefficients >= 0.65 between each other. Iltems in Factor 3 that have correlation coefficients >= 0.65 between each other.
4.4.1 Factor 1
Items, 'difficulty perfoming workhther activities'. 'took extra effort to
perfom workfother activities', and 'limited in the kind worklother activities you
have been able to do', had correlation coefficients of 2 0.65 between each other
as shown in table X (Appendix D), therefore they were addressed in the same
question.
Items, 'difficulty cleaning the bathroom', 'difficulty sitting with your family
during rneals', and 'diffÏculty maintaining interests and hobbies (like sports, arts
and crafts)' were omitted because they had low impact scores.
4.4.2 Factor 2
Items, 'irritable', 'grouchy', and 'moody' had correlation coefficients 2
0.65 between each other as shown in table XI (Appendix D). As a result they
were grouped together but they were excluded from the final questionnaire
because 'grouchy' had a low impact score. Items, 'feeling sad, unhappy',
'feeling depressed, gloomy', 'tearful', and 'feeling overwhelrned' were omitted
because these items had low impact scores.
Items. 'fed up with being sick', 'reassured that your symptoms are part of
normal pregnancy', and 'less interested in sex' were included into factor 2
because these items had high impact scores (shown in table II).
4.4.3 Factor 3
Items, 'worn out' and 'lack of energy' were grouped together into one
question since they had correlation coefficients r 0.65 shown in table XII
(Appendix D).
4.4.4 Factor 4
Items, 'sickness to your stomach', 'poor appetite', 'in the evening', and
hot eaten for longer than you would like' were included into factor 4 because
they had high impact scores (shown in table II). Items, 'nausea', Lomiting', and
'dry - heaves' also had high impact scores (shown in table II) but were also
included for face validity since we were constnicting an instrument for NVP.
4.5 NVP-HRQL QUESTIONNAIRE
Table VI shows the items that were used to construct the final NVP
HRQL Questionnaire shown in Appendix E. Items with high overall impact
scores were retained even if they did not result from the 4 - factor solution.
They were put into appropriate domains based on intuitive sense. Items that
were highly correlated were addressed in one question and items with low
impact scores were excluded from the final questionnaire given that we wanted
to develop a short and efficient instrument with items that had a great impact on
the women and which were likely to be responsive to changes in NVP in
individual patients. Other criteria were adequate representation of bath physical
and emotional function and a minimum of four items per domain in order to
decrease variability of response and reduce any impact or idiosyncratic
response to a given question. The domains were social/domestic/occupational
limitations (1 0 items), emotional health (7 items), fatigue (4 items), and physical
symptoms and their triggers (9 items) to give a total of 30 questions.
UUWYI-. -- Table VI : Items in their domains that made it to the final questionnaire -----------------------------------------------------------
Factor 1 (SociaVDornestic/Occupational Limitations) 1. Everything is an effort 2. Cut down on the arnount of tirne
spent at work or other activities 3, Accomplished less than you would like 4. Oitficulty preparing meals 5. Relying on your partner to do things you would
normally do for your farnily 6. Took longer to get things done than usual 7. Difficulty perforrning, took extra effort and lirnited in the kind of
worklother activities you have been able to do 8. Difficulty looking after the home 9. Difficulty shopping for food 10. Ditficulty maintaining your normal social
activities with family, friends, neighbors or social groups
Factor 2 (Emotional Health) 1. Feeling downhearted and blue 2. Cant enjoy your pregnancy 3. Frustrated 4. Emotional 5. Fed up with being sick 6. Less interested in sex 7. Reassured that your symptoms are part of normal pregnancy
Factor 3 (Fatigue) 1 . Fatigue 2. Worn out and lack of energy 3. Exhaustion 4. Tiredness
Factor 4 (Physical Symptoms and their triggers) 1 . Had certain foods 2. Exposed to certain smells 3. Nausea 4. Sickness to your stomach 5. Vomiting 6. Dry-Heâves 7. Poor Appetite 8. In the evening 9. Not eaten for longer than you would like
Issues in item presentation included time specification, response option
selection and whether the subjects should be shown their previous resp~nses~~ .
Time specification refers to the fact that patients are asked to think about how
they have been feeling over a well - defined tirne period. We used one week on
the intuitive impression that this time frame is reasonable of what patients can
accurately recall. Response options refer to the scale that is available for
responding to the questionnaire. An evaluative instrument must be responsive
to even small changes overtime therefore we chose a 7 - point scale to ensure
that relatively fine gradations of changes can be detected. Previous work
suggests that 7 - point scales combine excellent responsiveness with ease of
administration and patient ~ n d e r s t a n d i n g ~ ~ ~ ~ ~ . Subjects will be shown their
previous responses on follow-ups. This has been shown to improve validity of
89,N the questionnaire without affecting responsiveness .
The questionnaire will be analyzed directly from the scores recorded.
First the mean scores for the items within each domain will be calculated for
each subject. The overall quality of life score may be estimated from the mean
score for al1 the items. ln clinical trials the effectiveness of two or more
treatments rnay be compared using the mean within subject change in score for
each domain as well as for overall quality of life and this data may be analyzed
by parametric tests of inferencea2.
Section 5 DISCUSSION AND CONCLUSIONS
This study has addressed an unmet need for a tool that will describe the
full scaie morbidity of NVP. We have identified items of impairment in the day
to day lives of NVP patients. These have been used to develop a quality of life
questionnaire which should be applicable to al1 women with NVP and should be
responsive to within subject changes in Health-Related Quality of Life during
therapeutic intervention trials for NVP.
We have developed the first disease - specific HRQL instrument for
patients with NVP using a cornprehensive methodological framework
established from the development of other disease - specific i n s t r ~ r n e n t s ~ ~ ~ ~ ' ~ ~ ~ .
Our approach to item selection which utilized a variety of sources including
input from patients with diverse degrees of NVP was comprehensive and
ensured that we captured al1 important items. lnvolvement of 500 patients,
again with a variety of degrees of NVP in the item reduction process further
enhanced the content validity of our questionnaire. Designation of different
items into appropriate domains through a factor analysis ensured that the
domain scores represent specific aspects of HRQL.
ldentified items might have been expected to Vary among such a
heterogeneous group of patients. For instance, patients with severe NVP might
experience different limitations and types of impairment from those experienced
by patients with milder NVP. Anti - emetic therapy and occupation might also
be important determinants. Evaluating differences across strata of clinical NVP
severity was difficult because the measurement of severity is still controversial
to begin with as the condition itself can be very subjective.
The items did not Vary by age, parity, smoking, socio - economic, NVP
status and anti - emetic therapy indicating that one instrument is applicable to
ail segments of the population. What did Vary was the absolute magnitude of
the impact of NVP on daily life as refiected in the nurnber of people
experiencing problems and the importance they attached to these problems.
The finding that the total burden of quality of life impairment was greater in
patients with more severe NVP is intuitively sensible since they were attaching
a higher importance score to that specific item. The finding that quality of life
impairment was greater in patients taking more than one anti - emetics is also
sensible since anti - emetic usage is reflective of NVP severity.
Physical symptorns scores tended to be higher in general as compared
to the other 3 domains. However emotional and social, occupational functions
also had high scores and from the documented literature we know that NVP can
adversely affect women's lives 4.5.73.74.81
There are several limitations to this study. The interviews were done
over the telephone, hence the diagnosis of NVP is subjective as is the report by
the wornen. To account for this a 20 week follow - up was done to rule out
other causes of nausea and vomiting and ascertain that NVP was due to
pregnancy, however the reporting of NVP tends to be subjective as it is and
women will report how they are feeling based on their daily condition. The
sample population of women calling the Healthline is biased and consisted of
educated. fully - employed. Caucasian women who had no history of other
medical illnesses since these were excluded from the item - reduction
recruitrnent. These women were also on the severe end of the NVP spectrum.
The rneasurement of quality of life in patients is a subjective process.
First, many of the dimensions being assessed can not be directly physically
measured. Second, we are just as concerned with the patient's view of the
importance of the dysfunction as with its existence.
One of the drawbacks of the factor analysis is that there are many ways
to do both the factor extraction and rotation and therefore we may end up with
different results depending on the method we use. It also tends to use
subjective judgment in selecting the number of factors and naming the dornains
for the final solution. It's based on intuitive knowledge and sensibility. Intuition
however, has its limitations in grouping items because difference and
uncertainty as to where to place the specific item may arise. Another
disadvantage of using a factor analysis for item reduction is that items that are
not strongly associated with one of the factors are excluded from the final
questionnaire and it is possible that these items may be rated important by the
patients. However we included items that were highly rated by the women even
if they did not anse from the factor analysis to account for this. But this required
that we exclude certain items with low impact scores to ensure that we have a
short and comprehensive, final questionnaire.
One very important limitation of the new tool is the fact that it does not
measure non - pharmacotherapy such as hornecare, counseling and support
that can be beneficial in treating women with NVP especially in the
psychosocial realrn of the disease. Educating partners and family members
about NVP and how tc, offer support can be of great impact on these women's
I ives73.
Responsiveness and Validity data for the questionnaire are not yet
available. Despite this, we believe that there are several reasons why the
questionnaire can be used with confidence as a measure of outcome in new
clinical trials in NVP. Firstly, the way in which it was developed ensures content
validity in that it is comprehensive and represents domains that are important to
' NVP patients thernselves. Secondly as mentioned before, the process we have
used to construct the questionnaire is well e s t a b l i ~ h e d ~ ~ ~ ~ ~ ~ ~ ~ and has been used
successfully in constructing specific questionnaires for patients with asthma7',
chronic aidow ~imitations~~, heart failure7?, breast cancer treated with
che rn~ the ra~~ '~ , inflammatory bowel disease7' and chronic liver diseaseso. In
each case the questionnaire proved responsive and valid in formal testing.
There are possibilities that certain issues on the questionnaire may not
be responsive to intervention. The fatigue domain rnay be a problem that is
faced by pregnant women and not specific to NVP patients, therefore it may not
respond to anti - emetic therapy. Other items reported by the women such as
'can't enjoy the pregnancy' rnay travel in the opposite direction and may score
low on the new tool after an intervention. This may be a result of anti -
histamines' side - effects such as drowsiness which are often reported by NVP
patients. However the tool is describing aspects of the disease and its
treatrnent.
Full confidence in the questionnaire will have to wait assessrnent in
various clinical trials. We hope that other investigators will include this outcome
measure in their trials and report their findings from a variety of patient
populations and cultures.
Section 6 FUTURE DIRECTIONS
6.1 PRE-TESTING OF NVP-HRQL QUESTIONNAIRE
The aim of the pre - testing phase is to ensure that the final
questionnaire is free from wording erron and easily understood by both the
respondent and the interviewer; that respondents understand the intended
meaning of the questions; that the complete range of response options is used;
and that the format of the questionnaire is suitable for data analysis.
6.2 VALlDlTY AND RESPONSIVENESS
The new NVP - HRQL Questionnaire will have to be tested for its validity
and responsiveness. Responsiveness (an instrument's ability to detect change)
and validity (whether the instrument is measuring what is intended to measure)
are the measurement properties required of any HRQL evaluative instrument6*.
An evaluative instrument requires good responsi~eness~~. When there is
a change in the health state of the individual patient, the instrument must be
able to detect this change even if it is small. This change can occur
spontaneously or as a result of an intervention. To test responsiveness, one
can follow 3 strategies6*. One should be able to measure a change in patients
who truly change their health status. The instrument should also be able to
distinguish between those patients who change and those who stay stable and
its responsiveness index should have a high ratio of signal (magnitude of the
difference in score among patients who've changed) to noise (the change
among patients who've stayed the same)".
Part of the evaluation of any new instrument rnust be an assessment of
whether the instrument is actually measuring what it is supposed to measure6*.
Given that there is no gold standard for assessment of HRQL in NVP we will
have to evaluate construct validity by examining the relationship between
changes in overall HRQL and in each of the domains of the new instrument and
changes in other indices of irnpairment62.
6.3 SUMMARY
With the developrnent of such a validated tool to measure the symptoms
of NVP, clinicians will be able to measure efficacy and effectiveness of drugs
and other treatment modalities for NVP. lmplernenting the new tool in a variety
of research and clinical protocols will interest women's health and HRQL in
general, as well as the management of NVP specifically.
NVP is prevalent, and we have shown that it has an impact on quality of
life. This research effort, by addressing a major vacuum in the understanding of
NVP, will impact the lives of millions women, their farnilies, and society at large.
Section 7 REFERENCES
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5 3 ~ a n o t t a P, Magee L. Pharmacological and non - pharmacological management of NVP; a systematic critical review of the literature on safety and effetiveness of treatmemts (in press). "set0 A, Einarson T, & Koren G. Pregnancy outcome following first trimester exposure to anti-histamines: meta-analysis. Am J Perinatol 1997; 14: 1 19. 5 5 ~ c ~ e i g n e PM, Lam SH, Linn S, Kuthcer JS. Bendectin and birth defects: I. Meta -analysis of the epidemiologic studies. Teratology 1994; 50: 27-37. 56~ischer-~asmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of h peremesis gravidarum. Eur J Obst Gyn Rep Bio 1990; 38: 19-24. 'Nelson-Piercy C, de Swiet M. Corticosteroids for the treatment of h peremesis gravidarum. Br J Obstet Gynaecol 1994; 101 : 101 3-5. '&ells CN. Treatment of hyperemesis gravidarum with cortisone. Am J Obstet Gynecol 1953; 66: 598-601. 59~rugs in pregnancy and lactation. Briggs GG, Freman RK, Yaffe SJ (editors. Baltimore: Williams & Wilkins, 1 994; 579-82. 60~rugs in pregnancy and lactation. Briggs GG, Freman RK, Yaffe SJ (editors. Baltimore: Williams & Wil kins, 1 994; 642-3. 6'~inarson A, Koren G, Bergman U. Nausea and vomiting in pregnancy: a comparative study. Eur J Obs Gyn Repor Bio 1998; 76: 1-3. 62~chipper H. Clinch J, & Olweny C. Quality of life studies: definitions and conceptual issues. In: Quality of life assessment in clinical trials 2"d edition. Spilker B (ed). New York: Raven Press Ltd., 1996. 63~eiger GJ, Fahrenbach DM, Healey FJ. Bendectin in the treatment of NVP. Obst Gyn 1959; 14: 688-90. M ~ c ~ u i n n e s s BW, Taylor-Binns D. Debendox in pregnancy sickness. J R Coll Gen Prac 1971 ; 21 : 500-503. 65~heatley D. Treatment of pregnancy sickness. Br J Ob Gyn 1977; 84: 444- 47. 66~endectin Peer Group, Biol Basics International Peer Group Report, Merrell Dow Pharmaceuticals Inc., March 14, 1975, pp. 559-637. 67~indley CM, Hirsch JD, O'Neil CV, Transau MC, Gilbert CS, Osterhaus JT. Quality f life consequences of chemotherapy-induced emesis. Quality of Life Research 1992; 1 : 331 -40. 68~l iss JM, Robertson B, Selby PJ. The impact of nausea and vomiting upon
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Manotta P. Magee L, Koren G. Therapeutic Abortions due to severe rnorning sickness : an uacceptable combination. In: The Motherisk newsletter. Toronto: Motherisk, Fall 1996, no. 6. 76
dunniper E, Guyatt G, Epstein R et al. Evaluation of impairment of HRQL in asthma: development of a questionnaire for use in clinical trials. Thorax 1992; 47: 76-83. 76~uyatt GH, Townsend Mt Berman LB, Pugsley SO. Quality of life in patients with chronic airflow limitation. Br J of Dis of the Chest 1987; 81 : 45-54. 77~uyatt GH, Norgradi S, Halcrow S, Singer J, Sullivan MJJ, Fallen EL. Development and testing of a new measure of health status for clinical trials in heart failure. J Gen lntem Med 1989; 4: 101-7. 78~evine MN. Guyatt GH, Gent M, DePauws S, Goodyear MD. Quality of life in stage II breast cancer: an instrument for clinical trials. J Clin Oncol 1988: 6: 1 798-81 0. 79~uyat t GH, Mitchel A, h i n e EJ, Singer J, Goodacre R, Tompkins C. A new measure of health status for clinical trials in infiammatory bowel disease. Gastroenterol 1989; 96: 804-1 0. 80~ounossi ZM, Guyatt GH, Kiwi M et al. Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease. Gut 1999; 45: 295-300. "0 '~ r ien B. Naber S. Nausea and vomiting durhg pregnancy: effects on the uality of women's lives. BI RTH 1992; 19; 138.
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APPENDIX A
Item Reduction Questionnaire
NVP QUALITY OF LIFE QUESTIONNAIRE
niese qwstionnaires have been specioIZy designed to be opt icdy s c m e d Pieme mark each question wiih a &rk black I f you change your mind regarding an o v e r . p h s e first scribble over the incorrect m e r , then mark the conect m e r anà write your initiak beside if. For seandg purposes. pkase e m t e that your "x"'s or check marks do no? stray into my other boxes and pkae do not w d e in the borûèr of the page or on thc s p e d bar code ut the bottom of the page.
Date of interview 7
We are condueüng a shidy about the effects of naosea and vomiting of pregnancy, which we cali W. We wouid iike to interview women with NVP to leam more about how this condition affects women's Uves Might you be interested in pddpating in such an interview?
Yes => ( P h e proceed with the 'EIigibility criteria' questions.) /TJ No => (Please proceed with the 'Idigibiüty Interview Fonn '.)
Fint we need to ask you a few questions to determine if you qualify to participate in the study.
Tick al1 ofinnative responses
1. Are you cumntiy pregimt? e ~ e o m e . e e e m e e e m e ~ ~ m o ~ e o ~ o o ~ e o ~ o + ~ + ~ + o ~ ~ o o e . . o o ~ ~ e e o a e ~ e ~ o o o o o o +
2. Are you l e s than 12 weeks (3 rnonths) pregnant? o-o..o*..*~enn..u.oe~wom*eoo~omoem~~e~..i.....u...i.~~.o..ee~ a .... 3. Have you had nausea, vomithg or retehing pore than once, over the past week? 4. Are we correct in assuming that you have had no diarrhea to suggest that you have the au ?. 5. Cm we asmime that you have NO serious medical pmblems (e.g., asthma, diabetes
lupus, hem disease or lddaey disease)? ~ o w e ~ e m . - ~ - - u e . - . . o e o e ~ e o w ~ o ~ ~ e ~ t e - e ~ e m . . . m o o ~ o t o o o o +
6. Do you iradentand my English over the telephone? ...,...,...,,.,.,...~....~....~.o.e.~.oo~.9.~
&(rfQltSWer Y yeJ ta ail ofthe above, then plrase askfor consent to be interviewel)/
Consent to ~articipate
1. Wouid you be wüiing to be interviewed now for about 30 minutes? ................................................................................ Yes => a) Are yoa cornPortable? a m
......................................................................... b) Can you hear me ciearly? EH3 ............................................ c) Are yon in a quiet area fk of distractions? raxl
(If answers to ail of the above are Yes, then proceed if a w e r to any of the abuve is No, then piease skip to question e)
.............................................. d) Wouid you miod getting a pen and paper? Em You wiii need it for later Ln the interview (Skip to bareline doia on nctipage)
No => e) Wodd another time be more cùnvenient? a Y- Please specify a convenient thne E day of wk
timt of day a NO => ~ a n k y o u for OUT the, ( P k e p m c d wirh the 'Incügibility 'fomr)
Baseüne data
How would you rate the severity of your nausea and vomiting of pregriancy? (Please check ONE box) 0 Mild Moderate a Severe
Over the last week, how often have yon bad nausea? Always Most of the tune a Some of the time Ranly ornever
Over the iast w&, how o h h a ~ e yon fiad ~omitfag or r e t c b g ? a >5 timedd 2-5 timesld a ûnce per day Never
Before we interview you in detail, we need to ask you a few questions about yourself, NVP may Mer in dinerent cultures and ethnic groups. Wodd yon mind t e l u us how you would describe yourseif, based on the foiiowing choices: (Please check ONE box)
Caucasian a Black Oriental Asian (not Orientai) Latin Amcrican a Native Ametican
How would you describe your living arrangements, bas& on the following choices: (Please check ONE box)
Singk Married or living wiih your partna Separateci or divorrrd
a Widowed
How would you describe the ducation you have received? (Pieme check ONE box) Public rhool High school a Coilegehiversity a Post-graduate training
Have you b e n ushg tnstments other fhan medications for your nausea or vomiting? (Please check ONE box)
a =I If y=>, what have you been using? 0 Herbal remedies =====> >
Acupuncture or acupressure (e.g., Seabands) a -W~~=PY
Hypnosis Coining
a othcr > > (Please m m CO the Motktisk Telephone In& Fonn on the nurpage.)
MOTHERISK DEMOGRAPHICS
(To be removed before scanning) -
Patient's name: ( I Fit Name Las t Name
Telephone #: &I Home Work
Amnio? Yes No a Advised
Stable contact person: 7 1 LMonship: 1 1 Telephone numkr. 1 7
MOTBERISK PREGNANCY
EDC: -1 [7 by date 0 by ulmormd Day Montb Year
Most recent ulüasound in cumot pregnancy: Not yet a ar 0 wceks Reason: 7 1 Results: )I
Kicine y ................ El Heart .................. IHI Hypertension ......a Diabetes .............. (3 Respiratory ...-.... .tn] niyroid .............. El Psyctriatric .........a Epilepsy .............a
MOTHEXISK MEDICAL HISTORY
El El El El El Irl- O
r
l
During pregflanay
............... Alcobol E m I y ~ r i n k c i smoking ............. 17 0 [ l cigarettes
.............. Cocaint crack
- .................. Inlm
Marijuana -
........... Inla -
Item Reduction Questionnaire
Now we need to ask you about a long iist of things that you may or may not have exwrienceà as a renilt of vour nausea. vodtine or retching. You may feel îhat some of these questions do not apply to you, but it is important that we ssk the same ouestions of evenone. 1 aül read you a list of things that you may have experienced as a resuit of your na-, vomiting or retching. 1 wodd iike you to tell me if poo have q r i e n c e d any of the items over the iast week. Just aaswer "yes" or 'ho" after 1 read out each item. If you m e r I 'yeS', 1 would üke you to teii me how important that factor has been to you, by ushg the d e we have drslgned for this study. Would you please write d o m this d e to maLe il easier for yoursek
1. Not ai ai i an important factor (lfyou need to, explain t h t this means it is oniy a slight problem). 2. Not a verv important factor 3. An inimrtant factor 4. A fairiy important factor 5. A very important factor
Would you mind resdhg back to me abat you have written. 1 want to make sure that both of us are loaking at the same thing. (Pieme clanfy my errors). The amavers you have written d o m are numbered. You can respond to me by reading the number of your answer (for example, '3") or by usfng the wotds (for example, by saying, <'an important factor"). Fmm time to time throughout the interview, 1 wiil check to make sure that we are not making any mfstakes,
Do you have any questions More we begin? (Plearr clorify before beguuiing the interview).
We are now m d y to begh There are fonr sections to the questionnaire. The fïrst asks about how you have been feeling phvsiealiv. By ansvrering "y&' or "no", would yos please Lell me B you have experienced any of the followhg, due to vour nausea. vorniting or retching, over the last week* if you have experienced a symptom (for example, üredness) for some other mason besides nausea, vomfting or retching (for example, because your daughter has had a cold), thea please m e r 'ho" wfien 1 resd out that factar. (Please double-check the respomes to th j h t 3 finnative respunses. You do not have to go on checkhg if the patient has ma& no mistakes),
1. nausea ........................-.... ZIEl 2. dry-heaves ...................... lail 3. heutburn or indigestion .. 4. bad taste in your mouth ... a . . 5. vomimg .......................... ElEl 6. c h k s s ......................... E m 7. ~ L Y mouth ....................... E m
Very Fairly Not very importent importent Important important
VII
8. vomiting blood ................ mil 9. fatigue ............................. am 10. f e h g sick to your
stomach .......................... 11. l o s of weight .................. a
.............. 12. fecling wom out a 13. excessive saliva ............... ml 14. iackofcncrgy ................. C 0 15. dininiItyclimbing
..... s c v d a i g b ofstah O 0 i 6. buxping or belchhg ......... 17. discornfort (for exampic,
pain or cramping) in upper abdomen ............... 0
18. vomithg bide ................... 0 19. lightheadcdness ............... 20. exhaustion ....................... 0 2 1. diffidty playing sports ... 22. diacuitydriviagacar .....a 23. sleeping or napping for
most of the day ...............
25. sweaîhg .......................... 0 m ......................... 26. headache Em
27. poor appetite ..... .............. ml 28. feeling shaky ................... 29. admission to hospital .......O a 30. feeling out of brtath ........a 3 1. difiicuity nmning .............a 0 32. difficulty waiking W y .. m 33. dif£icuity climbing one
flight of scaas .................* O O 34. dificuity riding in a car ...O 35. sleeping p r l y ................ 0 36. constipation .................... ml 37. loose bowel movements ..a 0 38. passing gas ....................... ma 39. bmken blood vessels in
your eyes ........................ 0 El
Very Mrly Notvery Notatali, hpoitmt important Important important important
40. vaginal bleediog or SpOnUig ........................... O -
............. . 4 1 excessive hunger ma 42. excessive thirst ................ E m 43. sitîing for most of the
day .................................. 44. not caring for younelf as
you usudy do .................
vev Fairly ~ o t very ~ o t at all 1 important important Important Important important 1
Environmental stimuli
The wxt section deai~ with thtngs that may make your symptoms betîer or worse Couid you plesse teii me, over the iast week, if you have experlenad a worsenim of your nausea, vomithg or retching due to any of the foliowiag? If so, would you please rate how Important this factor has been to you, accordhg to the scale you've written dom. (Please double-check th responrcs tu thc f i rst 3 afinnative responses. You do not have to go on checking if the patient has made no
had cenain d&s ............ had certain foods ............. 0
............... wi th rnovement am ................. in the moniing mil
......... brushing your teeth 0 0 ..................... driven a car
not eaten for longer than you would iike ................ D you've changed position (like standing up h m sitting) ............................ a watcb;d certain things ..... a been in a hot or 'sniffy' m m ...............................a El traveUed by bus mil becn iying down .............. ElEl in the evening .................. m m been exposeci to certain SOM& .......................... ..m
................ travelled by car mil wtien you've been very cold ................................ 00
ver^ h i r l y Notvery NotataU 1 Important important Important important importani
El El a El
1 Y N 1 important important Important important important 1 17, ate or drank more than
........ p u normaUy wouid a a 1 18. üaveiled by brain or
subway ............................ 0 0 Il III I El E l 19. been exposed to certain
smus .............................. El El El LI LI El 20. in the afternoon ............... ma I l El El El 2 1. watched television or a 1
.............................. movie a a 1 a Could you pleace tell me, over the last week, if you have experienced an impmvernent in your nausea, vorniting or retching due to any of the followiag? If so, wodd you please rate how important this factor has been to you, according to the s d e you've written dom. (Ptearc double-check the respnses to fhcfnsr 3 afinnutive respamesS You do not have to go on checkhg if
at nst or s~cep ................. mil ........... when sitting down
g e h g frtsh air ............... Lm king in a dark, quiet m m ..................+............El El cating food ...................... ElEl exposed to certain sounds ............................ 0 m taking medication for n a w a and vomiting ........ in the evening .................. Em
taking fnquentt, smaii snacks ............................. a a a&r vomiting .................. IJEI chewing gwn ................... m m exposed to certain sights .. king distractecf by sornethiag or someone ....O in the morning ................. EIEI
ver^ Fairiy Notveq Notatall '
important important Important important important 1 El a a 121 El
18. comforted by your b
partner, fiiend, or f d y .. 0 a ............... 19. in the afternoon ma
20. eating solids and iiquids separately ........................ 0 0
21. using non-drug
acupuncture, Seabanch, ................. massage, etc.) El El
ver^ Fairly Notvery Notatall important important Important important important
Emotional fnncüon
The thini section deals with thoughts and feeiings. Could you please teii me if you have experienced any of the following thou~hts or feelin~s over the last week, as a rrsolt of vour nausea. vomiting or retching? If so, would you please rate how important that factor has been to you, according to the scale you've written dom. PIease mmember that if you have experienced one of the thoughtslfeeiing~ 1 r a d out, but you think it is because of something other than your nausea, vomiting or retching, then please amver "no" when I rwd out that particular item. (Pieuse double-check the responses to the fist 3 afinnative responres. You do not have to go on checking if the patient has made no mistakes).
womed about your health .............................. 0 feeling dowllhearted and blue ................................. [)l fal
feeling tbai life is not
f e h g h a î nothhg can chcer you up, that there
feeling that things are getîing you dom ............ 0 0
- -
ver^ Fairly Not very Not at aU important Important Important important important
veiy FairIy Not vev Not at aii important important Important important important
hopeiess, that things
discouragcd about the future .............................. am feeling that you are
................ behg punished can't enjoy yow prepancy .......................a El fnis trated ........................ n a worried that yow symptoms may tell other people you an pregnant beforie you want hem to know .............................. LE I reassured thai your symptoms an part of normai pregnancy ............ O O womed that there is something wrong with the baby .......................... 00 womed that you are rejecting Ihe pregnancy ...a worried that your symptoms may hm your baby ........................ a worried that yow medications may harm your baby ........................ a worried about having naiisealvomiting in a fuiure pregnancy ............. 0 0 regret about k ing pregnmt now .................. O hophg that you have a miscarnage ...................... wanting to end the pregnancy ....................... 0 El anxious ........................... ma guilty about having thought about ending the pfegnancy ....................... 0 O gtnlty about having
... hoped for a mirarriage
XII
26. that other people think that you are causing yocir OWQ sympoms ........El O
27, l e s concerneci about your physical appearanœ than m a l ........................ 0
28. guilty that you regret being pngnant ................O O
- -
29. nemous ........................... T;1 a 30. worried over liale tbings q 31. afraidhtyou will
vomit witbout warning ...................... or h ~ubiic
32. evu);huig is an egort ......a a 33. embarrassed about
excusing youIself in order to vomit ................. O
36. agitated ...................... .....a 37. initable ........................... am 38. grouchy ........................... mil 39. on edge ........................... a m 40. feelingugiy ..................... EKI 41. restiess ............................ am
............................ 42. moody EH3 43. short-tempered ................ ma 44. angry .............................. 0 0 45. feciing hostile towards
others ..............................O El 46. forgetfhi .......................... am 47. feeling that your
memory is not as good as it waUy is .................. III
........................ 48. emotional m m 49. tearful .....................*.........n 50. weepy ............................. ElEl 5 1. having troubIe maicing
decisions ......................... 0 52. kss intcrested in sac ........ 0 53, feeliog inadequatt, like a
weak pason ....................a
- --
ver~ Fairly Notvery Notataii Important important Important important important
disgustcd with yo m i f ....a ....... feeling ovawheimed 0
feeling iike you are loshg controi ..................a fetiing that you are falling to pieces ............... 0
mmething awful is going cl-
to happen ........................ LL] iA ....... anaid to eat or drink
confused ......................... t feeling iike a dependent person, helplcss ...............m &able to care for yourself ........................... 0 0 feeling Iike a burden to other people .................... unable to cope ................. mil
..... fed up with king sick guilty about not spending as much tirne with your pmer ............ guilty about not spending as much time
.............. with your f d y 0 guilty about not spending as much time with your fÎiends ............. 0 0 womed that you wiii lose your job ................... feeling that there is no one you ue dose to ........ 0 0 feeling that you are isolated h m famiiy and fnends ............................. a misled about what it is likt to have nausca, vomiting or retching in pregnaocy .......................El El loaeiy .............................. 0 feeling that the days seuntodrag ................... O El
veiy Fairly Not very Not at ail important importent Important important important .
R n m
Sociai/dornestic/oecu~ationaI function
This fourth and last section deah with yoar social. home or work We. Would you plem tell me (by m e r i n g "yes" or no") if any of the foilowing have been a problem for you, over the lPst week, as a resuit of vour nausea vomitinr or retching. If any item hm been a probiem for you, would you please rate how important that item has been to you, acmding to the seale you've written down. (Pierise double-check the responses tu the first 3 ufinnarive responses. You do not hmie to go on checking ifthe patient bas ma& no mistakes).
i~ N cut down on the amount of time you spent at work or other activi ties ............. a accomplished l e s than you wouid like ................. 0 0
helpl&, unable to help you .................................. 0 0 forgtnul .......................... ElEl lost time h m paid work .. a your partner feeling fmstrated .......................... 0 partner is lcss interestcd in sex .............................
relying on your partner to do things you wouid normaliy do for your M y ...........*.................. 0 0
10. took longer to get things donc than usud ................
1 1. partner thinlcs ihk is part of nonnai pregnancy ........ 0
12. diflicdty thinloag clearly .. 17 f 3. difficuity with your
relationship with your chitdren ........................... 0
14. ~ c u l t y performing work/other activities ........ a
15. difIicuity deaning the bathmm ......................... a
16. took extra effort to perform work.other activities .......................... a
ver^ Fairly Not verg Not at aU important important Important important important
17. di&cultysolving day to &y pmblems ................... a
18. &GcultYdoiîgl~dry .... m 0 19. iimited in the kind of
workfother activities you have been able to do ........
20. difnculty concentrating on what you are doing ..... a things tfit way you usuaiiy do ........................
22. diffic& iooking &r the home ............................... a
........... 23. partner is conhrsed 24. hardship on those closest
to you .............................. 0 0 25. difnculty shopping for
food ................................. 0 El 26. diffidty Sitting with yom
family duhg meals .......... 0 0 27. difliculty warhiDg dishes .. 28. difficulty maintaining
your n o r d social activities with family, friends, neighbors, or social p u p s ................... UEI
29. difnculty in your relation- ship with your partner ......
30. partner is angry about your nausta, vomiting or ntching .......................... 0 0
3 1. difficulty maintahhg htcnsts and hobbies (like sports, arts and crafts) ..... 0 0
32, financial difficuitics (due directly to your symptoms or their mtment) ............ 0 .
33. problems with your
summef, weekcnds away, winter breaks) .................. E m
ver^ Fairly Not ve ry Not at ail important important Important important important
Qosine
We are finished the questionnaire! T M you very much for your patience!.
1. More we end the interview, wodd you pleace teil me if the diagnosis of nausea and vomithg of pregnancy has been confhed by your doctor (either yoiu M y doctor or your obstetrician)?
Yes No
2. May we EPU p u bad: nt about 5 montbs of p r q q to see how yoa are Bdhg? The d wlll take l e s than 5 minutes. (Pieme proceed with iite questàons below.)
Would anoîher tirne be mare convdent? Yes => Plesse spedFg a convenient tlme 1-1 &y of wk I I time of day No => Thfink you very much for your tirne.
(PIeme put the file A ~ h e 20 week foümvÿp foldcr for call-bock and mu& the &te on t h calendar. I f patienî Ls 16 weeks' gesîation or mure, then mnnC a &te k t is 4 weekfrom the rUnc of thc first phone call).
Thank you very mu& for giving us your the. Do you have any questions you would iike to ask us? (Pieuse document the conversaiibn in the space beùw).
20 week follow-IIP cal1
Date of Interview 7 I 1 1 1
Day Month Ycar
Interviewer r
As 1 am sure you d, you spoke with (m of hienimer) from the Nausea and Vomiting of Pregnancy Bealthline in (mcmth and year of first Urterview)
regarùing your nausea and vomiting of pregnancy. At that time, you indieated h t it wodd be okay for someone h m the Heaithiine to d you Dack and tuid out how you are feeling.
Wodd you have two minutes to speak with me? Yes => (Pkiue proceed with the questions below.)
@ No => Wodd another t h e be more convenient? a Yes => Pleese speeify s eonvenient time F I day of wk F I tirne of day
No => Thank you for your tirne.
Has your doctor (family doctor or obstetrician) said that you hadmaoe nausea and vomiting of pregnancy?
Yes
No => Wouid you mind telhg us the explmation they had for your nausea, vomiting or retching?
When is your baby due?
Are you carrying twins or triplets?
Are you stiii baving nausea, vomiting or retching? Yes No
Tbaak you once again for your the. May we caii yon back after the birîh of yonr baby to see how you are feeling? The cal1 wii i take appmximteiy 15 minutes.
a YCS => PI- sperify a co~mnient time r j of wk [-1 tllne of day 101 NO => Tb8ak you very much for your time.
(Please put the file in the post-natal foIfaw-up folder for caii-back and mark the date on the calendar).
Guidelines for Conducting Telephone Interviews
Guidelines for Telephone Interview
For the first interview, begin by introducing yourself to the respondent and ensure that this is a good time for the intewiew to take place. You rnay wish to talk a little with the patient to put them at ease, then start into the interview. You will note the interview begins with ensuring the patient is in an appropriate environment for the intewiew, and has everything available that she or he needs. For follow-up interviews you can remind the patients who you are, make sure you have found a good time for the interview, and then begin.
Below are suggestions to keep in mind when conducting the intewiew over the telephone.
Ensure that the respondent is in a quiet area of their home free of distractions. (Exarnple - Television or Radio tumed off. Kettle/stove off and dinner preparations not needing attending. Other family memben out of area).
Make sure respondent has al1 the necessary information with them to complete the interview, the response cards and activity list.
Ensure that the respondent is cornfortable, has reading glasses, a drink of water.
Can the respondent hear you and can you hear them clearly over the telephone. 1s the line static free. You may need to call back if it is a bad connection.
Ensure that the respondent has 20 to 30 minutes to spend answering the questionnaire (first administration). 15 minutes if it is then follow up.
Ask respondents if they have cal1 waiting service; if so decide how you can deal with a call, if they receive one during the interview. One option is to suggest that if the respondent needs to answer the cal1 they do it quickly asking the new caller to cal1 back later. The interviewer should then repeat the entire question they were on when the cal1 first came through.
Speak clearly and slowly when asking the questions. Allow enough time for the respondent to answer the questions. Repeat the question if the patient seems uncertain or does not understand something.
If respondents have difficulty holding the telephone in one hand and the cards in the other, suggest that they lay the cards out in front of them and only pick up the color card that they needs for that question.
Ensure that respondents have the nght colored card in front of them for each question. This is written into the questionnaire but if you need reassurance that they have the correct card, you could repeat the color of the card in your question, i.e. by choosing a response from the orange card. Another alternative is to ask the respondent what Ietter is in the top right hand corner of the card. AH this is especially important in color blind patients.
APPENDIX C
Five-Point Likert Scale
FIVE-POINT LIKERT SCALE
ver^ Fairly Not Very Not at Al1 Yes No lmportant Important lmportant Important Important
APPENDIX D
Factor Analysis Results
Table VII: 3 - factor solution using a varimax rotation for al1 66 items with impact score 2 2.0'
factor 1 factor 2 factor 3 (nausea - sociaL/domestid (ernotional health) (fatigue) occupational limitations)
nausea feeling downhearted fatigue not caring for yourçelf as you and &tue worn out
usually do feeling sad and unhappy lack of energy everything is an effort feeling depressed and exhaustion cut down on the amount of time gioomy tiredness
you spent at work or other can't enjoy your pregnancy activities frustrated
accomplished less than you would irritable like grouchy
difficulty preparing rneals moody relying on your partner to do things emotional
you would normally do for your tearful famiIy overwhelmed
took longer to get things done than usual
difficulty performing worWother activities
difficulty cleaning the bathroom took extra effort to perform workl
other activities limited in the kind of workfother
activities you have been able to do difficulty looking after the home difficulty shopping for food diff iculty preparing meals diff iculty maintaining your normal social
activities with family, friends, neighbors or social groups
difficulty rnaintaining interests, hobbies (like sports, arts and crafts
- - - - - - -
O All items presented have factor loadings > 0.5 therefore associated with that factor.
Table VllI- Rotated factor loadings for the 3 - factor mode1 for al1 66 items with impact score 12.0'
sympiom **
ps0l ps02 ps04 ps05 ps09 psl0 ps12 psl4 ps16 ps20 ps23 ps24 ps27 ps3S ps42 ps43 ps44 es02 es03 es04 es05 es07 es1 O es1 3 es19 es20 e fol e f 02 e f O3 e f O4 ef08 e f l l ef12 ef14 ef18 efl9 ef27 ef31 e f 32
Factor 1
0,52041 0.37202 0.26426 0.251 45 0.12903 0.34327 0.181 97 0.19053 0.14106 O. 14967 0.1 81 73 0.1 5642 0.39801 0.1 4626 0.1 5754 0.37977 0.49865 0.32272 0.48463 0.2791 7 0.27857 0.2821 7 0.1 8948 0.35285 0.41 989 0.37679 O, 1 4823 0.2071 9 0.1 2878 0.1 3538 -0.1 7763 0.34907 0.39756 0.037 19 0.31 61 7 0.1 4726 0.42302 0.26256 0.55505 ----- -- -
'AI1 nurnbers presented are factor loadings for each item in each factor. " List of symptoms can be found in Appendix A.
Table VIII- Rotated factor Ioadings for the 3 - factor model for al1 66 items with impact score 2 2.0' (cont'd) - - Symptom "
ef37 ef38 ef42 ef40 ef49 ef52 ef57 ef67 ef68 ef69 ef76 sdofOl sdof02 sdof03 sdof08 sdof 09 sdof 1 O sdofl 1 sdofl4 sdofl5 sdofl6 sdofl9 sdof22 sdof25 sdof26 sdof28 sdof31 ----------------m_-__+----i----w-----------------------------------------
*Al1 numbers presented are factor loadings for each item in each factor. '* List of symptoms can be found in Appendix A.
Table IX: Rotated factor loadings for the 4 - factor model for al1 66 items with impact score 2 2.0*
Symptom **
psOl ps02 ps04 ps05 ps09 ps l O ps12 ps14 ps16 ps20 ps23 ps24 ps27 ps35 ps42 ps43 P S ~ es02 es03 es04 es05 es07 es1 O es1 3 es1 9 es20 ef O 1 ef 02 ef O3 ef O4 e f O8 e f l 1 ef12 ef14 ef l8 ef l9 ef27
'AI1 numbers presented are factor loadings for each item in each factor. " List of symptoms can be found in Appendix A.
Table IX: Rotated factor loadings for the 4 - factor rnodel for al1 66 items with impact score r 2.0' (cont'd)
Symptom "
ef31 ef32 ef37 ef 38 ef42 ef48 ef49 ef 52 ef 57 ef 67 ef68 ef69 eff 6 sdof0l sdof02 sdof03 sdof08 sdof09 sdofl O sdofl1 sdofl4 sdofl5 sdofl6 sdofl9 sdof22 sdof25 sdof26 sdof28 sdof31
*Ali numbers presented are factor loadings for each item in each factor, " List of symptoms can be found in Appendix A.
Figure 2 : Scree Plot of Eigenvalues for al1 66 items with impact score r 2.0'
0 5 10 15 20 25 30 35 40 45 50 55 60 65 Factors
Using al1 items with an impact score r 2.0 resulted in 66 factors. '" Eigenvalues describe the amount of variance explained by each factor.
ef32
sdof0 1
sdof02
sdof08
sdofO9
sdof 7 O
sdof 14
sdof 7 O
0.47666 <.O001 498
0.30770 <.O001 499
0.51 368 <.O001 499
0.44547 <.O001 499
0.431 59 <.O001 499
1.00000
499
0.42431 <.O001 499
sdof 14
0.501 77 <.O001 499
0.5321 7 <.O001 500
0,50468 <.O001 500
0.31 674 <.O001 500
0.26632 <.O001 500
0.42431 <.O001 499
1.00000
500
sdof 15 sdof 16 sdof 19 sdof22 sdof25
XXX
~ ~ ~ ~ ~ ~ ~ o ~ ~ . ~ ~ ~ " o o ~ ~ ~ ~ - ~ ~ - - - - - ~ - - - ~ - ~ ~ - ~ - - ~ - - ~ - - - - ~ ~ - - ~ - ~ ~ - - - o - - ~ - - ~ - - - - ~ - - ~ - ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ . o ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
Table X: Pearson correlation coefficients for the 15 items with impact score 2 2.0 for factor 1 for the 4 - factor model*(cont'd) -------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------
sdof
sdoil6
sdof 19
sdof22
sdof25
sdof26
sdofO2 sdof08 sdof09 sdof 1 O sdof 14 sdof 15 sdof 16 sdoil9 sdof22 sdof25
XXXI
Table X: Pearson correlation coefficients for the 15 items with impact score 2 2.0 for factor 1 for the 4 - factor model*(cont'd)
ef32
sdof0 1
sdof02
sdof08
sdof09
sdof 1 O
sdofl4
sdof 15
sdofl6
sdofi9
- - - - - - - -
*See table V for the 4 - factor solution. See Appendix A for the items' names.
- - -------------------
Table X: Pearson correlation coefficients for the 15 items with impact score 2 2.0 for factor 1 for the 4 - factor rnodel*(cont'd)
'See table V for the 4 - factor solution. See Appendix A for the items' names.
ef02 ef03 efO4 efl l ef12 ef37 et38 ef42 ef48 ef49 tif57
*See table V for the 4 - factor solution. See Appendix A for the items' names.
XXXV
F r = z * m q o 0 v -
Table XII: Pearson correlation coefficients for the 5 items with impact score 2 2.0 for factor 3 for the 4 - factor model* -
'See table V for the 4 - factor solution. See Appendix A for the items' names.
Table XIII: Pearson correlation coefficients for the 2 items with impact score 2 2.0 for factor 4 for the 4 - factor model' d
'See table V for the 4 - factor solution. See Appendix A for the items' names.
APPENDIX E
NVP HRQL Questionnaire
Nausea and Vomiting in Pregnancy Quality of Life Questionnaire
This questionnaire has 30 questions and it has been designed to find out how you have been feeling during the last week. You will be asked about your syrnptoms related to your nausea and vomiting in pregnancy, how you have been affected in doing activities, and how your mood has been. Please complete al1 of the questions and select only one response for each question.
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. Al1 of the time the lime the time the time the tirne the time the time
2. How often did you have vomiting in the past week?
1. None of 2. Hadly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. Al1 of the time the time the time the time the time the time the time
3. How often did you have dry heaves in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. Al1 of the time the time the time the time the time the time the tirne
4. How often did you experience sickness to your stomach in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the time ihe tinte the time the time the time the time
5. How often did it take you longer to get things done than usual as a result of your nausea, vomiting in pregnancy in the past week?
1. None of 2. Hardly any of 3. A Iittle of 4. Some of 5. A good bit of 6. Most of 7. Ail of the time the time the time the time the time the time the time
6. How often in the past week have you had difficulty or you have been limited or it has taken you extra effort to perform work and other activities as a result of your nausea, vomiting in pregnancy?
1. None of 2, Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. Al1 of the time the time the time the time the time the time the time
7. How often have you felt downhearted or blue as a result of your nausea, vomiting of pregnancy in the past week?
1. None of 2. Hardly any of 3. A little of 4. Sorne of 5. A good bit of 6. Most of 7. Al1 of the time the time the time the time the time the time the time
8. How often in the past week did you feel worn out and had lack of energy as a result of your nausea, vomiting in pregnancy?
1. None of 2. Hardly any of 3. A Iittle of 4. Sorne of 5. A good bit of 6. Most of 7. Alf of thetime the time thetime the time the time the time thetime
9. How often in the past week did you have poor appetite as result of your nausea and vomiting in pregnancy?
1. None of 2. Harûly any of 3. A litüe of 4. Some of S. A good bit of 6. Most of 7. All of the tirne the tirne the time the tirne the time the tirne the time
1 O. How often in the past week have you had difficulty maintaining your normal social activities with family, friends, neighbors or social groups as a result of your nausea, vomiting in pregnancy?
1. None of 2. Hardly any of 3. A tittle of 4. Some of S. A good bit of 6. Most of 7. All of tne rime riie ume tne Ume h u m e the Urne tne time (ne urne
11. How often in the past week did you experience nausea and vomiting in pregnancy in the evening?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the tirne the time the time the tirne the time the time
12. How often have you felt frustrated as a result of your nausea, vomiting of pregnancy in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5, A good bit of 6. Most of 7. All of the tirne the tirne the time the time the time the time the time
13. How often did you feel exhaustion as a result of your nausea, vomiting of pregnancy in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the time the time the time the time the time the time
14. How often as result of your nausea and vomiting in pregnancy, in the past week have you had to rely on your partner to do things you would normally do for your family?
1. None of 2. Hardly any of 3. A little of 4. Some of S. A good bit of 6. Most of 7. All of the time the time the time the time the t h e the time the time
15. How often in the past week have you felt fed up with being sick as result of your nausea and vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Sorne of S. A good bit of 6. Most of 7. Al1 of the time the t h e the tirne the time the time the time the time
16. How often in the past week have you had difficulty looking after the home as a result of your nausea, vorniting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of S. A good bit of 6. Most of 7. Al1 of the time the time the time the tirne the time the time the time
17. How often have you had difficulty shopping for food in the past week as result of your nausea and vomiting in pregnancy?
1. None of 2. HardIy any of 3. A little of 4. Some of S. A good bit of 6. Most of 7. All of the time thetime thetirne thetime the time the time the time
18. How often did you feel tiredness as a result of your nausea, vomiting of pregnancy in the past week?
1. None of 2, Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. Al1 of the time the time the time the time the time the time the time
19. How often in the past week did you not eat for Ionger than you wouid like as result of your nausea and vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of !!!r 5me 'he !me !!!e Ume !!!o Ume !ke Urne 'he 9me !!!e 5rt.e
20. How often in the past week did you feel reassured that your symptorns are part of normal pregnancy?
1, None of 2. Hardly any of 3. A liffle of 4. Some of 5. A good bit of 6. Most of 7. All of the lime the time the time the time the time the lime the time
21. How often did you feel tess interested in sex in the past week as a result of your nausea, vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the time the time the time the time the time the time
22. How often did you feel fatigue as a result of your nausea, vomiting in pregnancy in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. AI1 of the time the time the tirne the time the time the time the time
23. How often have you felt emotional as a result of your nausea, vomiting of pregnancy in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. AI1 of the time the time the time the time the time the time the time
24, How often in the past week have you felt that you have accomplished less than you would like as a result of your nausea, vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of S. A good bit of 6. Most of 7. All of the time the time the time the time the time the tir.e the time
25. How often have you cut down on the amount of time you spent at work or other activities in the past week as result of your nausea and vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the îime the tirne the time the time the time the time the time
26. How often in the past week did you experience nausea and vomiting from being exposed to certain smells?
1. None of 2 Hardly any of 3. A liffle of 4. Some of S. A good bit of 6. Most of 7. All of thetirne the tirne the time thetime the time the time the tirne
27, How often in the past week have you felt that everything is an effort as result of your nausea and vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the time the time the tirne the time the time the time
28. How often have you felt that you cant enjoy your pregnancy as a result of your nausea, vomiting of pregnancy in the past week?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the time the time the time the time the time the time
29. How often in the past week did you experience nausea and vomiting from being exposed to certain foods?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. Al1 of the time the time thetime thetirne thetime the time the tirne
30. How often in the past week have you had difficulty preparing or cooking meals as result of your nausea and vomiting in pregnancy?
1. None of 2. Hardly any of 3. A little of 4. Some of 5. A good bit of 6. Most of 7. All of the time the time the time the time the time the time the tirne
