THE USE OF HERBAL MEDICINES DURING PREGNANCY AND PERINATAL MORTALITY

7/28/2019 THE USE OF HERBAL MEDICINES DURING PREGNANCY AND PERINATAL MORTALITY

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SO U T H E A S T A SIAN J T R O P M ED P UBL IC H EALTH

1150 Vol 38 N o. 6 N ovember 2007

THE USE O F HER BA L M ED IC INES D UR I NG PR EG NA NC Y

AND PER INATAL M O R TALITY IN TU M PAT D ISTR IC T,

K ELANTAN , M ALAYS IA

A zriani Ab R ahman1, Zulkifli A hmad1, Lin Naing2, Siti A mrah Sulaiman3,

A bdul M anaf H amid1 and Wan Nudri Wan Daud1

1D epartment of C ommunity M edicine, 2School of Dental Sciences, 3D epartments of

P harmacology, S chool of M edical Sciences, H ealth C ampus, U niversiti Sains M alaysia,

K ubang K rian, K elantan, M alaysia

Abstract. T he objective of this case-control study was to determine the association between

herbal medicine use during pregnancy and perinatal mortality in Tumpat D istrict, K elantan,

M alaysia. C ases were mothers who gave birth from June 2002 to June 2005 with a history of

perinatal mortality, while controls were those without a history of perinatal infant mortality. A

total of 316 mothers (106 cases and 210 controls) were interviewed. T he use of unidentified

herbs prepared by traditional midwives and other types of herbal medicines during the first

trimester of pregnancy were positively associated with perinatal mortality (O R = 5.24, 95%

C I= 1.13; 24.23 and O R = 8.90, 95% , C I= 1.35; 58.53, respectively). T he use of unidentified

O rang Asli herbs and coconut oi l during the third trimester of pregnancy were negatively

associated with perinatal mortality in Tumpat (O R = 0.10, 95% C I= 0.02; 0.59 and O R = 0.48,

95% C I= 0.25; 0. 92, respectively). T hese findings suggest the use of unidentified O rang Asli

herbs and coconut o il in late pregnancy are protective against perinatal mortality, while the use

of unidentified herbs prepared by traditional midwives and other types of herbal medicines in

early pregnancy has an increased risk of perinatal infant mortality. P harmacological studies to

confirm and identify the compounds in these herbs and their effects on the fetus should be

conducted in the future.

crown rump heel length equal to or greater

than 25 cm, or early neonatal death (0-6 days)

(M O H , 2000). In 2000, the perinatal mortality

rate was 47 per 1,000 births in the world

(WH O , 2006). In the study area, Tumpat, the

perinatal mortality rate in 2003 was 13.68 per

1,000 births (K elantan State Health Depart-ment, 2004) which was higher than the rate in

K elantan (11.59 per 1,000 births) (K elantan

State Health Department, 2004) and in M a-

laysia overall (9.1 per 1,000 births) (M O H ,

2004). Several factors, such as low maternal

educational level, low household income, too

young and too old m others, primi parity,

grandmultiparity and maternal diseases have

been among the factors found to be associ-

ated with perinatal death (K liegman. 1998). A l-

C orrespondence: D r Azriani Ab R ahman, D epart-

ment of C ommunity M edicine, S chool of M edical

Sciences, Health C ampus, U niversiti Sains M alay-

sia, 16150 Kubang Krian, K elantan, M alaysia.

Fax: 609-765 3370

E-mail : azriani@ kb. usm.m y

I N T R O D U C T I O N

H erbal medicines are defined as plant-

derived material or preparations with therapeu-

tic benefits, and contain raw or processed in-

gredients from one or more plants (WH O ,

2000). T he use of herbal medicines duringpregnancy is common, ranging from 7.0 to

55.0% (T iran, 2003). P erinatal mortality is

defined as death of a fetus weighing at least

500 g or born after 22 weeks gestation or a


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H E R BA L M EDICINES A N D P ERINATAL M ORTAL I TY

Vol 38 No. 6 November 2007 1151

though there are no published studies directly

linking herbal medicine use in pregnancy with

perinatal death, several studies have found

herbal medicine use in pregnancy is associ-

ated with congenital malformations (Takei etal, 1997; C han et al, 2003; N oordalilati et al,

2004), intrauterine growth retardation, de-

creased fetal survival rates (Sulaiman et al,

2001), low birth weight (M orris and M dlalose,

1991), fetal distress (M abina et al, 1997), fetal

hypoxia and premature delivery as a results

of uterine hyperstimulation (Veale et al, 1998),

which may lead to perinatal mortality.

T he objective of this study was to deter-

mine the association between herbal medicineuse in pregnancy and perinatal mortality in

Tumpat D istrict, K elantan, M alaysia.

M AT E R IA L S A ND M ET HO DS

Tumpat D istrict is one of ten districts in

K elantan. It is a costal area, about 21 km from

K ota Bharu, the capital of K elantan and about

1 km from the Thai border. M ost of the people

there are farmers or fishermen. T he majorityare M alays.

A case-control study was carried out in

2005. T he inclusion criteria for cases were

women who gave birth from June 2002 to

June 2005, who were recorded in the birth

registration records of Tumpat District and had

a history of perinatal mortality. T he inclusion

criteria for controls were those with no history

of perinatal mortality, giving birth during the

same period of time. A ll cases who fulfilled theinclusion criteria were included. A simple ran-

dom sampling method was used to select

controls. A sample size calculation was done

using PS Software, version 1.0.13 (Dupont

and P lummer, 1997). Tak ing a significance

level of 0.05, a study power of 80% , a detect-

able odds ratio of 2.0 (women with a history

of perinatal mortality were 2.0 times more likely

to use herbal medicines during pregnancy

compared to those without perinatal mortal-

ity), a proportion of herbal medicine exposure

among controls of 0.46 (estimated by the pro-

portion of herbal medicine use during preg-

nancy among women attending antenatal clin-

ics, H ospital Universiti Sains M alaysia) and aratio of cases to controls of 2, the minimum

sample size required was 300 subjects, 100

cases and 200 controls.

T he patients were interviewed using a

structured questionnaire by the first author.

T he interviewer gave a definition of herbal

medicines to the mothers. In this study, moth-

ers were considered herbal medicines users

if they took herbal medicines orally in any form,

such as solutions, capsules, tablets or in rawform, at any amount during any trimester of

pregnancy. P reparations consumed as nutri-

ments or as food additives were not consid-

ered as herbal medicines. T he patients were

also asked whether they had taken herbal

medicines before they conceived. For those

who took herbal medicines before becoming

pregnant, they were asked to recall the last

time they took the medicines to determine

whether they were taken during pregnancy. Tohelp mothers to recall, a list of commonly used

herbal medicines was shown to the subjects

as examples. A list of common indications for

using herbal medicines was also shown and

the subjects who were asked whether any

herbal medicines had been used. Local tradi-

tional midwives, homeopathy practitioners and

pharmacists were interviewed in an effort to

confirm whether the products were herbal

medicine products and to identify the specificherbal contents of the products.

Sociodemographic and maternal disease

variables of the cases and controls were tabu-

lated for descriptive statistics. B inary logistic

regression was used to determine the asso-

ciation between the use of herbal medicines

during pregnancy and perinatal mortality ad-

justing for the known risk factors. D espite

many factors that are known to be associated

with perinatal mortality, only some of the


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1152 Vol 38 N o. 6 N ovember 2007

factors were included in our study. The se-

lected factors were those in which accurate

information could be obtained from available

research tools or textbooks. T he selected fac-

tors were parity, maternal disease, age, totalhousehold monthly income, race, education,

husband smok ing status, patient smok ing sta-

tus, multiple pregnancy, H IV and syphilis in-

fection. T he preliminary main effects model

was fit by the independent variables, includ-

ing herbal medicine use, as research ques-

tion variables and all known risk factors ad-

just ing for variables. M odel fi tness wa s

checked by the H osmer-Lemeshow good-

ness-of-fit test and R O C curve. Influentialcases were identified by influential statistics,

namely delta beta, delta chi square and delta

deviance. A case was considered an influen-

tial outlier if delta beta 1, delta chi-square

and delta deviance 4 (H osmer, 2000). R e-

sults were analyzed using Stata version 8.

This study was approved by the R esearch

and Ethics C ommittee, Universiti Sains M a-

laysia (U SM ) and M inistry of Health, M alaysia.

RESULTS

All 316 mothers (106 cases and 210 con-

trols) consented to be interviewed. Table 1

showed the sociodemographic and maternal

characteristics for cases and controls. C ases

were older and had greater parity. A higher

proportion of cases had maternal disease and

multiple pregnancies. T he cases had lower

educational level. A lower proportion of moth-ers who were housewives was observed

among cases. The total monthly household

income was lower among cases. T here were

no significant differences in race, marital sta-

tus or spouse smoking between cases and

controls. A ll the mothers were non-smok ers.

H IV and VD R L were negative for all mothers.

T here were 41 cases (38.7% ) and 108

controls (51.4% ) who used at least one type

of herbal medicine during pregnancy in this

study. T he most common herbal medicine

used by cases (46.3% ) and controls (63.9% )

in this study was coconut oil, which was in-

gested during the third trimester of pregnancy

only. The most common indication for usingherbal medicines during pregnancy among

cases (61.0% ) and controls (89.8% ) was to

facilitate labor.

Simple logistic regression (Table 2) re-

vealed significant herbal variables were the use

of unidentified O rang Asli herbs and coco-

nut oil during the third trimester of pregnancy

and the use of unidentified herbs prepared by

traditional midwives during the first trimester

of pregnancy.

O n multiple logistic regression (Table 3),

the significant herbal variables after adjust-

ing for parity, maternal disease, age, income,

race, education and husband smoking sta-

tus were the use of unidentified O rang Asli

herbs and coconut oil during the third trimes-

ter of pregnancy, the use of unidentified herbs

prepared by traditional midwives and other

types of herbal medicines during the first tri-

mester of pregnancy. T he use of unidentified

O rang Asli herbs and coconut oil during the

third trimester of pregnancy was protective

for perinatal mortality. T he odds of perinatal

mortality for mothers who took the unidenti-

fied O rang Asli herbs was 90.0% less (O R

= 0.10). T he odds of perinatal mortality for

those who took coconut oil was 52.0% less

than those who did not take it (O R = 0.48).

T he use of unidentified herbs prepared by

traditional midwives and other types of herbal

medicines during the first trimester of preg-

nancy were positively associated with peri-

natal mortality. T hose who used unidentified

herbs prepared by traditional midwives dur-

ing the first trimester of pregnancy were 5.24

times more likely of having perinatal mortal-

ity. T hose who used other types of herbal

medicines during the first trimester of preg-

nancy were 8.90 times more likely of having

perinatal mortality.


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Variables C ases C ontrols Test statistic p-value

n= 106 n= 210 (df)a

Age (years) 33.5 (7.77)b 30.5 (6.54) b -3.42d (182) 0.001 d

25-34 34 (32.1) c 111 (52.9) c 17.98e (2)


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1154 Vol 38 N o. 6 N ovember 2007

Unidentified O rang Asli herbs in 2 (1.9) 21 (10.0) 0.17 0.04, .75 0.004

3rd trimester

C oconut oil in 3rd trimester 19 (17.9) 69 (32.9) 0.45 0.25, .79 0.004

Unidentified herbs prepared by 7 (6.6) 4 (1.9) 3.64 1.04, 12.73 0.038

traditional midwives in 1st trimester

U nidentified herbs prepared by traditional 1 (0.9) 8 (3.8) 0.24 0.03, 1.95 0.114

midwives in 2nd or 3rd trimester

O ther types of herbal medicines in 8 (7.5) 8 (3.8) 2.06 0.75, 5.66 0.164

1st trimesterd


2nd trimestere


3rd trimesterf

Sanggul Kacip Fatimah in 3rd trimester 3 (2.8) 6 (2.9) 0.99 0.24, 4.04 0.989

O ther types of K acip Fatimah 6 (5.7) 7 (3.3) 1.74 0.57, 5.31 0.337

(Labisia patoina, pumila) in 1st trimester

K etam Uri use in 2nd or 3rd trimester 3 (2.8) 2 (1.0) 3.03 0.50, 18.41 0.223

M anjakani ( Croton caudatus) use in 1 (0.9) 3 (1.4) 0.65 0.07, 6.39 0.709

1st trimester

Table 2

U se of herbal medicines during pregnancy and perinatal mortality analysed by simple

binary logistic regression.

Variables (use of specific types of

herbal medicines in specific trimester

of pregnancy)

C ase

(n=106)

n (% )

C ontrol

(n = 210)

n (% )

C rude

O R a

95% C I

O R b

p-value

of

LR Statc

a C rudeodds ratio; bC onfidence interval of odds ratio; cLik elihood ratio statistic; dother types of herbal medi-

cines used during 1st trimester of pregnancy include celaka (Plumbago zeylonica) root (n= 3), gelam

(Melacieuca cajupati) leaf (n=1), tongkat ali (Eurycoma longifolia jack) juice (n= 1), sirih (Piper bettle) leaf

(n= 1), stunjang bumi (Prismatomeris tetranda) root ( (n= 1), mas secotek (Ficus d eltoides) (n= 1), mata

kucing Keling fruit (n= 1), pineapple fruit (n=1), M engkudu (Mo rinda elliptica) juice (n=1), ganoderma

(n= 1), tongkui root (n=1), boiled juice of durian skin (n= 1), coconut juice (n=2), kembang semangkuk

(Scaphium macropod um) flower (n= 1), sea weed (n=1), gingko (Gingko biloba) fruit (n= 1), tamar fruit (n=1);eother types of herbal medicines used during 2nd trimester of pregnancy, include ganoderma (n= 3), sea

weed (n= 1), tamar fruit (n= 2), gingko (Gingko biloba) fruit (n= 1), tongkat ali (Eurycoma longifolia jack)

(n=1), mengkudu (Mo rinda elliptica) juice (n= 1), mata kucing keling fruit (n=1); fother types of herbal

medicines used during 3rd trimester of pregnancy, include coconut juice (n= 2), ganoderma (n= 2), seaweed (n= 1), tamar fruit (n= 2), boiled juice of durian skin (n= 2), tongkat ali (Eurycoma longifolia jack)

(n=1), k embang semangkuk (Scaphium macropod um) flower (n= 1), mengkudu (Morinda elliptica) juice

(n= 1), mata kucing keling fruit (n= 1), gingko (Gingko biloba) fruit (n= 1)

complications, such as post-term pregnancy

and prolonged labor, which are known to be

contributing factors to fetal death. There may

be benefits of these herbs in facilitating labor

and reducing intrapartum complications, which

are not currently known. However, this inter-

esting finding should be confirmed by pharma-

cological study to identify the compounds in

these herbs and to evaluate the effects of these

compounds on the fetus.


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Variables (use of specific types of herbal medicines Adj 95% C I O Rc p-value of

in specific trimester of pregnancy) O R b LR Statd

Unidentified O rang Asli herbs in 3rd trimester

No 1.00 0.001

Yes 0.10 0.02, 0.59

C oconut oil in 3rd trimester

No 1.00 0.024

Yes 0.48 0.25, 0.92

Unidentified herbs prepared by traditional midwives in 1st trimester

No 1.00 0.029

Yes 5.24 1.13, 24.23

O ther types of herbal medicines in 1st trimester e

No 1.00 0.017Yes 8.90 1.35, 58.53

Unidentified herbs prepared by traditional midwives in 2nd or 3rd trimester

No 1.00 0.160

Yes 0.24 0.02, 2.40

O ther types of herbal medicines in 2nd trimesterf

No 1.00 0.056

Yes 0.03 0.00, 1.11

O ther types of herbal medicines in 3rd trimesterg

No 1.00 0.311

Yes 3.56 0.28, 45.41

Sanggul Kacip Fatimah in 3rd trimester

No 1.00 0.817Yes 1.21 0.25, 5.87

O ther types of K acip Fatimah (Labisia pumila, patoina) in 1st trimester

No 1.00 0.306

Yes 1.97 0.54, 7.25

O ther types of herbal medicines in 3rd trimesterg

No 1.00 0.311

Yes 3.56 0.28, 45.41

K etam Uri in 2nd or 3rd trimester

No 1.00 0.101

Yes 7.74 0.64, 93.32

M anjakani (Croton caudatus) in 1st trimester

No 1.00 0.855

Yes 0.80 0.07, 9.25

Table 3

U se of herbal medicines during pregnancy and perinatal mortality analysed by multiple

binary logistic regressiona

aadjusted for parity, maternal diseases, age, income, race, education, spouse smok ing status; bAdjusted

odds ratio; cC onfidence interval of adjusted odds ratio; dLik elihood ratio statistic H osmer-Lemeshow good-

ness-of-fit statistics chi-square p-value = 0.557. R O C curve = 0.803.No influential outliers identified.

T his study measured perinatal mortality

as a birth outcome, while other studies fo-

cused on perinatal morbidity, which can lead

to perinatal mortality. Several studies found

that herbal medicines taken to facilitate labor

caused adverse fetal effects. In South A frica,

fetal distress was related to the consumption

of local herbal medicines taken to facilitate


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1156 Vol 38 N o. 6 N ovember 2007

labor. About 55.6% of mothers using herbal

medicines had meconium staining of amniotic

fluid, an indication of fetal distress (M abina et

al,1997). In another study, G lover et al(2003)

reported uterine hyperstimulation occurred at39 weeks of gestation when a mother took

black cohosh to induce labor . T he infant

suffered from fetal distress and thick meco-

nium aspiration. Traditional herbal medicines

can lead to strong, continuous uterine con-

tractions not corresponding to the slow dila-

tation of the cervix. As a result, they may cause

acidosis in the mother, followed by fetal dis-

tress (Rolanda and Sally, 2006). M econium-

stained amniotic fluid is associated with peri-natal asphyxia and meconium aspiration syn-

drome (M AS). M econium aspiration is one of

the most common causes of perinatal mortal-

ity (K liegman, 1998). L aboratory studies found

that Isihlambezo, a traditional herbal medicine

used to stimulate the tonicity and frequency

of uterine contractions, augments the effects

of oxytocin on isolated rat uterus. Used inap-

propriately, it may lead to premature labor

(Varga and Veale, 1997), which is anothercommon cause of perinatal mortality

(K liegman, 1998). In our study, many mothers

ingested unidentified O rang Asli herbs and

coconut oil at term, before the onset of labor.

As these herbal medicines are generally taken

only at term, the possibility of premature de-

livery is avoided. H owever, our study was not

able to rule out the possibility of uterine hy-

perstimulation induced by these herbs. The

mothers took only one tablet of unidentifiedO rang Asli herbs, while they took only one

teaspoon or table spoon of coconut oil. T he

practice of consuming herbal medicines in

relatively small doses at term is unlikely to

cause adverse effects on the fetus. T he health

impact of herbal medicines is highly depen-

dent on amount, concentration and stage of

pregnancy (Varga and Veale, 1997).

We found the use of unidentified herbs

prepared by traditional midwives and other

types of herbal medicines during the first tri-

mester of pregnancy were risk factors for peri-

natal morta lity. T hese herbs may contain

chemical compounds which may be teratog-

enic. Exposure of the embryo to teratogensduring the first trimester of pregnancy may

cause congenital anomalies because fetal tis-

sues and organ systems are developing rap-

idly during this period (M oore, 1998). A local

herb, Andrographis paniculata(Hempedu bumi)

given orally to rats during early pregnancy

caused teratogenic effects leading to major

congenital malformations (N oordalilati et al,

2004). C ongenital malformations are a common

cause of perinatal mortality (K liegman, 1998).In K elantan, congenital malformations cause

17.7% of perinatal mortality in 2001 (K elantan

State Health Department, 2001).

T his study suggests some herbs are

harmful, while others may be protective for the

fetus. T hese findings should be confirmed by

conducting further studies to identify pharma-

cological compounds of these herbs and

evaluate the effects of these compounds on

the fetus.

A C K N O WL ED G E M EN T S

We thank the Universiti of Sains M alaysia

for a short term grant, all the maternal and

child health clinic staff in the Tumpat D istrict

and the mothers who participated in this study.

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THE USE OF HERBAL MEDICINES DURING PREGNANCY AND PERINATAL MORTALITY