6
Discussion: ‘Microcephaly associated with congenital heart defect’ by Barbu et al In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Barbu D, Mert I, Kruger M, Bahado-Singh RO. Evidence of fetal central nervous system injury in isolated congenital heart defect: microcephaly at birth. Am J Obstet Gynecol 2009;201:43.e1-7. DISCUSSION QUESTIONS What was the study question? What was the study design? How were cases and controls identified? Do the conclusions correspond with earlier work? Why are these findings biologically plausible? What challenges accompany a prospective study design? What might be the best antenatal testing in this population? How will these findings shape patient counseling and care? I NTRODUCTION Congenital heart defects (CHDs) occur in about 1% of live births, according to the American Heart Association. Most obste- tricians know little about the long-term outcome of babies with a prenatal diagno- sis of CHD. Aside from cardiac disorders, these patients have a higher than expected incidence of neurodevelopmental delay. While this may be related to neonatal and childhood incidents, including intraoper- ative events during corrective cardiac sur- gery, a growing body of medical literature points to possible in utero origins. A new study discussed in this month’s meeting of the Journal Club used microcephaly as a marker for intrauterine damage to the cen- tral nervous system. Isabelle Wilkins, MD and George A. Macones, MD, MSCE BACKGROUND Wilkins: Why did the authors think that it was important to perform this study? How does it fit into our understanding of perinatal aspects of congenital heart disease? Colon: There have been reports in the literature of central nervous system (CNS) abnormalities in children with a CHD. Although some experts believe that these abnormalities are associated with corrective cardiac surgery, interest has developed in a possible intrauterine role. In 1996, researchers reported an in- creased rate of cerebral atrophy in new- borns with CHDs compared to healthy full-term controls. 1 At the time of the study, these children had not had any cardiac surgery. Similarly, a study in 2000 noted increased rates of micro- cephaly and neurologic dysfunction in newborns who had an isolated CHD. 2 One large population-based study also found a possible association between congenital heart disease and head-size abnormalities. 3 However, not all of the literature supports this; a 1989 study showed no significant reduction in birthweight, length, or head circumfer- ence in infants with an isolated CHD. 4 Altered hemodynamics from CHDs— particularly, altered blood flow to the brain— offer a possible etiology for such abnormalities. Reduced oxygenation can lead to poor brain development. Studies using prenatal pulsed Doppler velocimetry in fetuses with CHDs have shown modifi- cations in the fetal cerebral circulation. Kaltman and colleagues showed a de- creased middle cerebral artery (MCA) pul- satility index in fetuses with hypoplastic left heart syndrome when compared with normal fetuses. 5 They also noted an in- creased MCA pulsatility index in fetuses with right-sided obstructive lesions. Wilkins: What was their study question? Qato: Their primary study question: are fetuses with isolated CHDs at increased risk of microcephaly, and if so, what are the specific types of cardiac lesions that could be associated with newborn microcephaly. Wilkins: How would you restate that as a hypothesis? Qato: Their hypothesis is that fetuses with isolated CHDs are at increased risk for newborn microcephaly, and in par- ticular, cyanotic lesions are significantly associated with microcephaly. S TUDY DESIGN Wilkins: What type of study design have the investigators used to look at this hypothesis? Colon: This was a single-center retro- spective case-control study. Usually case-control studies are used to identify From the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Illinois College of Medicine at Chicago, Chicago, IL: Moderator Isabelle Wilkins, MD Professor and Director Discussants Maria Colon, MD Fellow Meredith Cruz, MD Fourth-year resident Roa Qato, MD Third-year resident Jennifer Damlich Fourth-year medical student 0002-9378/$36.00 © 2009 Published by Mosby, Inc. doi: 10.1016/j.ajog.2009.05.042 See related article, page 43 For a summary and analysis of this discussion, see page 118 Journal Club Roundtable www. AJOG.org JULY 2009 American Journal of Obstetrics & Gynecology e7

Discussion: ‘Microcephaly associated with congenital heart defect’ by Barbu et al

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Page 1: Discussion: ‘Microcephaly associated with congenital heart defect’ by Barbu et al

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Journal Club Roundtable www.AJOG.org

iscussion: ‘Microcephaly associated with congenitaleart defect’ by Barbu et al

n the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications

or future research. Article discussed:

arbu D, Mert I, Kruger M, Bahado-Singh RO. Evidence of fetal central nervous system injury in isolated congenital heart defect: microcephaly at birth.

m J Obstet Gynecol 2009;201:43.e1-7.

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DISCUSSION QUESTIONS

What was the study question?

What was the study design?

How were cases and controlsidentified?

Do the conclusions correspond withearlier work?

Why are these findings biologicallyplausible?

What challenges accompany aprospective study design?

What might be the best antenataltesting in this population?

How will these findings shape patientcounseling and care?

rom the Department of Obstetrics andynecology, Division of Maternal-Fetaledicine, University of Illinois College ofedicine at Chicago, Chicago, IL:

oderatorsabelle Wilkins, MDrofessor and Director

iscussantsaria Colon, MD

ellow

eredith Cruz, MDourth-year resident

oa Qato, MDhird-year resident

ennifer Damlichourth-year medical student

002-9378/$36.002009 Published by Mosby, Inc.

oi: 10.1016/j.ajog.2009.05.042

See related article, page 43

For a summary and analysis of this

Odiscussion, see page 118

NTRODUCTIONongenital heart defects (CHDs) occur inbout 1% of live births, according to themerican Heart Association. Most obste-

ricians know little about the long-termutcome of babies with a prenatal diagno-is of CHD. Aside from cardiac disorders,hese patients have a higher than expectedncidence of neurodevelopmental delay.

hile this may be related to neonatal andhildhood incidents, including intraoper-tive events during corrective cardiac sur-ery, a growing body of medical literatureoints to possible in utero origins. A newtudy discussed in this month’s meeting ofhe Journal Club used microcephaly as a

arker for intrauterine damage to the cen-ral nervous system.

Isabelle Wilkins, MD andGeorge A. Macones, MD, MSCE

ACKGROUNDilkins: Why did the authors think

hat it was important to perform thistudy? How does it fit into ournderstanding of perinatal aspects ofongenital heart disease?olon: There have been reports in the

iterature of central nervous systemCNS) abnormalities in children with aHD. Although some experts believe

hat these abnormalities are associatedith corrective cardiac surgery, interestas developed in a possible intrauterineole. In 1996, researchers reported an in-reased rate of cerebral atrophy in new-orns with CHDs compared to healthyull-term controls.1 At the time of thetudy, these children had not had anyardiac surgery. Similarly, a study in000 noted increased rates of micro-ephaly and neurologic dysfunction inewborns who had an isolated CHD.2

ne large population-based study also c

JULY 2009 Am

ound a possible association betweenongenital heart disease and head-sizebnormalities.3 However, not all of theiterature supports this; a 1989 studyhowed no significant reduction inirthweight, length, or head circumfer-nce in infants with an isolated CHD.4

Altered hemodynamics from CHDs—articularly, altered blood flow to therain—offer a possible etiology for suchbnormalities. Reduced oxygenation canead to poor brain development. Studiessing prenatal pulsed Doppler velocimetry

n fetuses with CHDs have shown modifi-ations in the fetal cerebral circulation.altman and colleagues showed a de-

reased middle cerebral artery (MCA) pul-atility index in fetuses with hypoplasticeft heart syndrome when compared withormal fetuses.5 They also noted an in-reased MCA pulsatility index in fetusesith right-sided obstructive lesions.ilkins: What was their study

uestion?ato: Their primary study question: are

etuses with isolated CHDs at increasedisk of microcephaly, and if so, what are thepecific types of cardiac lesions that coulde associated with newborn microcephaly.

ilkins: How would you restate thats a hypothesis?ato: Their hypothesis is that fetusesith isolated CHDs are at increased risk

or newborn microcephaly, and in par-icular, cyanotic lesions are significantlyssociated with microcephaly.

TUDY DESIGNilkins: What type of study design

ave the investigators used to look athis hypothesis?olon: This was a single-center retro-

pective case-control study. Usually

ase-control studies are used to identify

erican Journal of Obstetrics & Gynecology e7

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Journal Club Roundtable www.AJOG.org

e

actors that may contribute to a condi-ion; in this study, microcephaly. Theategorical variable is an outcome of in-erest, and then the variables that are as-ociated with this outcome are analyzed.ase-control studies are good for assess-

ng rare outcomes, like microcephaly.lso, they are usually less time-consum-

ng and require a smaller sample sizehan prospective cohort studies. How-ver, they are subject to bias even whenhey are retrospective in nature. One po-ential type is selection bias. This may bentroduced with selection or inclusion ofhe controls and the cases. One of the

ost important sources of bias is infor-ation bias. Because the data collection

s performed retrospectively, the accu-acy of the data that is collected may note optimal or may not be equal for allases and controls.

ilkins: How did they collect the caseshat they studied?

amlich: This is a hospital-based retro-pective case-control study using dataollected from the International Classifi-ation of Diseases, 9th revision, Clinical

odification codes of babies diagnosedith a CHD at Children’s Hospital ofichigan. Data were extracted from de-

iveries that occurred between January 1,998 and March 31, 2007. The studyases, 401 babies, had any of the follow-ng types of heart defects: transpositionf the great arteries, tetralogy of Fallot,oarctation, ventricular septal defectVSD), aortic stenosis, interrupted aor-ic arch, double outlet right ventricle,runcus arteriosus, total anomalous pul-

onary venous drainage, atrioventricu-ar septal defect, aortic valve atresia, aor-ic arch hypoplasia, hypoplastic left oright ventricle, or pulmonary valve ste-osis. Babies were excluded from the study

f they had a small or minor VSD, chromo-omal defects, extracardiac anomalies,enetic syndromes, or were from a mul-iple gestation.

ilkins: How did they collect theirontrol group?ruz: The control group of 401 babiesas born at Hutzel Hospital within 3onths of the study index case. Cases

nd controls were matched by gender,ace, and proximity of their birth dates.

ontrols had a gestational age at birth e

8 American Journal of Obstetrics & Gynecology J

hat was within 1 week of the index studyase, no structural anomalies, no sus-ected or confirmed genetic defects, andhey were not from multiple gestations.

ilkins: Were the exclusion criteriaisely chosen?ruz: Their exclusion criteria were ap-ropriate, as they excluded babies withther potential causes for microcephaly.

ilkins: If they had used a prospectivetudy design, what further data wouldou have liked to see them collect?amlich: I would have liked them to col-

ect in utero cranial measurements at dif-erent gestational ages to determinehen there is evidence of decreased head

ircumference. They could have also hadlarger sample size for the various typesf heart lesions. This would increase theower and provide a better idea of statis-ical significance. It would also be helpfulo do fetal echocardiograms and hemo-ynamic Doppler ultrasonography atarious gestational ages. If it were possi-le to follow these infants over time, theyould have assessed whether the headircumference normalized as the childrew and if there were any cognitive oreurologic deficits associated with mi-rocephaly.

ilkins: So you would like to be ableo track when this problem starts?

amlich: Yes. It would be nice to seehen the heart defect becomes evidentersus when you notice that the head cir-umference is abnormal. I would followhese infants after birth to see if they nor-

alize over time or if they have impair-ents from the microcephaly and/or the

eart defects.ilkins: What data would you collect

uring the pregnancy?amlich: As noted, retrospective studies

re dependent on patient recall for a lotf data. If you collect it prospectively,ou may be getting more accurate infor-ation regarding use of tobacco or

rugs, especially cocaine. You can alsoee if the women have any other medicalllnesses, and you can monitor morelosely or consistently for medical com-lications, such as diabetes and hyper-ension.olon: You are describing recall bias, butam not sure that there is much of inter-

st that the mother can’t remember. Ob- y

ULY 2009

iously, they can underestimate when re-orting tobacco and drug use, but that islso true if the data are collected prospec-ively. If we were collecting the data forhis study prospectively, I would want toee whether or not the difference in theead circumference can be detected pre-atally. If so, I would like to know when

t first became noticeable and whether itoincided with a prenatal diagnosis of in-rauterine growth retardation (IUGR).id it start happening at the same gesta-

ional age? Or did the microcephaly hap-en first? This could help determinehether the IUGR is contributing to theiagnosis of microcephaly.

ilkins: What is the differenceetween the univariate andultivariate analysis?ruz: A univariate analysis explores eachariable in a data set separately to iden-ify any factors that may be significantlyssociated with the outcome of interest.nce these significant factors are identi-ed, they are then entered into a logisticegression analysis, or a multivariatenalysis, to identify independent factorshat are significantly associated with theutcome of interest. In other words, aultivariate analysis involves observa-

ion and analysis of more than 1 statisti-al variable at a time, which is more rep-esentative of reality when multipleariables are usually associated with theutcome of interest.

ilkins: Was the size of the studyample appropriate?olon: It was interesting that they men-

ioned the power analysis in their resultsather than in their methods. It meanshat they did the power analysis afterhey found all of their cases, in order toee if the study was going to be bignough. They calculated a sample size of56 subjects: 128 controls and 128 cases.heir goal was to detect a 10% increased

ate of microcephaly in the CHD group.ith this number of subjects, they

ould have had a power of 80% for thistudy. Usually, for a sample-size calcula-ion, you need to know the incidence ofhe outcome of interest, which in thisase is microcephaly, as well as the ex-ected difference between the 2 groupsnd the level of statistical significance

ou want for the P value. Although the
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www.AJOG.org Journal Club Roundtable

uthors don’t mention the frequencyhat they used for the outcome or whathey thought the frequency for micro-ephaly was in their population, it ap-ears that by using the sample popula-ion they described, the study wasdequately powered.

ilkins: That is true for theypothesis related to the rate oficrocephaly overall in the CHD

roup. Was there any other hypothesishat you told us about?

ato: Yes, there was; the researchersanted to determine what specific typesf cardiac lesions were associated with an

ncreased risk for microcephaly. Thatould have required a separate sample-

ize calculation for each of those cardiacesions. This was not done; the sampleize calculation was for CHDs overall.

ilkins: We may need a separate powernalysis if the rate of microcephaly is veryifferent in 1 subgroup and we want to ex-mine that group separately. Approxi-ately 128 patients are needed in order toeet their criteria for a well-powered

tudy. So if those subgroups had signifi-antly below 128 patients, we may have aroblem later as we get to the results.ato: I agree.

ESULTS

ilkins: What do Tables 1 and 2 saybout the population studied?amlich: Table 1 assesses the maternalemographics. In both groups, most ofhe mothers were either Caucasian or Af-ican American, most did not have med-cal or obstetrical complications, and

ost did not use tobacco or other drugs.n terms of comparing the mothers of theabies with CHDs to the normal con-rols, there is a statistically significantifference in age between the mothers ofHD cases and the controls (28.2 vs 26.5ears, respectively; P � .001). There wereo other significant differences regard-

ng parity, race, medical conditions, orbstetrical complications.

ilkins: What did you think abouthe difference in diabetes ratesetween the 2 groups?olon: It looks like it is approaching sig-

ificance, since the P value was 0.054. i

hat was interesting but something thatou would expect, because obviously,others with diabetes are at higher risk

or babies with CHDs. So, it didn’t strikee as strange.ilkins: If that difference had been

ignificant, would it change ournterpretation of the results at all?olon: For me, it would not. I don’t

hink that diabetes is a risk factor for mi-rocephaly, so I think the only way itould affect the rate of microcephaly is if

here was something else, like a CHD,hich could lead to it.ilkins: I don’t know of any reason to

hink that fetal heart disease resultingrom maternal diabetes is different fromhe same heart disease caused by some-hing else. So, although there are differ-nces in the 2 populations, it is only sig-ificant if it is going to change the

nterpretation of our results.ilkins: What about Table 2?

amlich: Table 2 lists the rate of occur-ence for each type of CHD. The mostommon defects were VSD, coarctation/ortic arch hypoplasia, d-transpositionf the great artery, and hypoplastic rightentricle, together accounting for 76.1%f cases.

ilkins: Any surprises there? Did well know that VSD would be the mostommon CHD? I can’t say that Iealized that coarctation would be theecond most common.ato: I thought it would be the hypo-lastic left ventricle. I feel like I’ve seenhat much more frequently.

ilkins: This raises the issue of whethere make these diagnoses equally fre-uently in utero. We will get back to thisoint later.

ilkins: Which of the findings inable 3 was significant and whichere not?ato: In Table 3, we find that infantsith tetralogy of Fallot, coarctation/aor-

ic arch hypoplasia, and hypoplastic leftentricle showed a statistically signifi-ant increase in the incidence of micro-ephaly compared to the control group.he remaining infants with specificHDs did not show a different risk foricrocephaly in comparison with those

n the normal group. o

JULY 2009 Am

ilkins: Maria, 1 of the articles youited in the beginning showedicrocephaly was associated with

oarctation and VSD. Here, in thistudy, microcephaly is associated withoarctation but not VSD. Would youse this to reassure patients that VSD

s not associated? Or do you think thathe jury is still out?olon: I think that we need more studies

o be sure. In the study by Van Houten, Ion’t recall the number of patients withSD, but it is possible that they had more

ases in the study and were able to see atatistically significant difference in theate of microcephaly between the normalnfants and the babies with VSD. In otherords, the problem may be that the cur-

ent study is underpowered to detect aifference in the subcategory of VSD.

ilkins: What is shown in Table 4?ruz: Table 3 showed that patients with

etralogy of Fallot, coarctation/aorticrch hypoplasia, and hypoplastic lefteart demonstrated a significantlyigher frequency of microcephaly com-ared to the overall normal group. Tableregroups the cases of heart disease byhether they are cyanotic CHD, mixing

ype lesions, or right-sided obstructiveisorders. They demonstrated increasedates of microcephaly in comparison toontrols.

ilkins: Why is the association withmall-for-gestational-age (SGA)eonates as explored in Table 5

mportant?ato: In Table 5, the authors tried to

ontrol for the confounding variable ofGA, as SGA itself may increase the riskor microcephaly. They removed all SGAewborns from the analysis, and the re-ult showed that coarctation/aortic archypoplasia was still associated signifi-antly with microcephaly. However, al-hough hypoplastic left ventricle and hy-oplastic right ventricle both had aoubling of the rate for microcephaly,either finding was statistically signifi-ant. That may be because they had tooew cases.

ilkins: Why do you think thatetralogy of Fallot was no longerignificant?ato: There may have been too few cases

f tetralogy of Fallot to have reached sta-

erican Journal of Obstetrics & Gynecology e9

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Journal Club Roundtable www.AJOG.org

e

istical significance— or maybe micro-ephaly was more often explained byGA. Maybe a lot of those babies weremall overall instead of having just amall head size.

ilkins: What conclusions can weake from the univariate analysis inable 6? How did the authors use this

nformation to perform a logisticegression analysis?ruz: Table 6 demonstrates the results

rom a series of univariate analyses,hich were performed to identify poten-

ial factors that correlated with newbornicrocephaly. A threshold of P � .10 was

sed in the univariate analysis to identifyndependent variables for inclusion inhe logistic regression analysis for signif-cant independent predictors of micro-ephaly. A stepwise binary logistic re-ression analysis then confirmed thatirthweight was a significant indepen-ent predictor of newborn microceph-ly. Therefore, being born with a birth-eight that is appropriate for gestational

ge reduces the risk of microcephaly. Te-ralogy of Fallot and coarctation/aorticrch hypoplasia were the specific cardiacnatomical defects that significantly andndependently correlated with micro-ephaly in the newborns. The presence ofither of these cardiac defects indepen-ently increased the risk of microcephalyy more than 2.5 fold.

ilkins: Are we surprised thatirthweight is independently related tohe rate of microcephaly?

ato: The diagnosis of microcephaly isade by measuring head circumference

nd comparing it with gestational age.maller babies are going to have smalleread circumference. So if the baby ismall all over, it’s going to have a smalleread size.olon: You can see this in the research-

rs’ odds ratio calculation, as well. Thedds ratio is less than 1, meaning thatigher birthweight is protective againsticrocephaly.ilkins: P was significant if it was less

han .1. Why didn’t they use the moreommon .05 or .01?ruz: When you do a univariate analysis,our P value is usually higher than whatou ordinarily use in studies. This is

one to identify the variables that are to l

10 American Journal of Obstetrics & Gynecology

e entered into the multivariable analy-is.

ONCLUSIONS

ilkins: What have the authorsoncluded from their study?amlich: Overall, the authors have con-

luded that CHDs, particularly cyanoticesions, can result in microcephaly. Thisuggests that a cyanotic defect can causeeurologic damage to a fetus in utero.

ilkins: How does this correspondith previous literature on this

ubject?ruz: In this study, an isolated CHD in

he fetus was associated with an in-reased risk of microcephaly, and micro-ephaly has long been known to correlateith mental retardation. The findings

re consistent with results from previoustudies indicating that high rates of CNSbnormalities occur in children withHDs. Prior studies have also demon-

trated a significant relationship betweenhe type of CHD and microcephaly.

oreover, previous studies of fetaloppler ultrasonography have demon-

trated significant hemodynamic changesn the cerebral circulation of fetuses with

CHD, and such changes could ulti-ately cause decreased brain growth.ilkins: What physiologic factorsake these findings biologically

lausible?olon: It is known that fetal autoregula-

ory mechanisms alter resistance in theerebrovascular system in response tohanges in oxygen delivery. Studies innimals and humans show that a de-rease in cerebrovascular resistance oc-urs to compensate for fetal hypoxemia.

e can assume that some CHDs causelterations in the oxygen content of thelood being delivered to the brain, whichay then affect brain development.In normal fetal cardiac anatomy,

ighly oxygenated blood from the duc-us venosus is preferentially shuntedcross the foramen ovale to the left ven-ricle, ascending aorta, and cerebral cir-ulation. Some cardiac defects, includingetralogy of Fallot, coarctation of theorta, and hypoplastic left ventricle, willause intracardiac mixing of blood, thus

owering the oxygen content of the blood y

JULY 2009

eing delivered to the brain. Also, somef these lesions cause blood delivered tohe brain to come from the ductus arte-iosus in a retrograde fashion.

Cerebral Doppler studies supporthese physiologic factors as possible eti-logies for alterations in CNS develop-ent. Studies by Kaltman, Modena, andonofrio found changes in the middle

erebral artery (MCA) pulsatility indexnd cerebral-to-placental resistance ra-io; these can be thought of as compen-atory mechanisms for the alterations inxygenated blood delivery.5-7

ilkins: What would you like to seehe authors add to their study designf they were able to perform arospective follow-up study?amlich: I would like them to look more

losely at each type of heart lesion, gath-ring enough cases to increase the powerf the study. I’d also like to see morehorough monitoring of the pregnan-ies, since they relied on recall for therst study. More frequent and more fo-used imaging throughout the entireregnancy would help in terms of defin-

ng when the cardiac defect begins to af-ect the head circumference. It wouldlso be helpful to know if the severity ofhe lesion influences the head circumfer-nce and if so, how much. More exactiming, along with follow-up data afterirth, would allow the authors to maketronger recommendations in terms ofatient management.

ilkins: What would be some of thehallenges of a prospective studyesign?ruz: A prospective study design, which

ollows groups over time, involves moreesources and is generally more expen-ive. Prospective studies are more sus-eptible to bias by differential loss to fol-ow-up and the lack of control over riskssignments. But the strength of a pro-pective study is that you can examine

ultiple effects of a single exposure andctually do measurements of the inci-ence of the disease or the factor that were looking at. In this study, I am con-erned about the accuracy of the diagno-is. At what point do we make a diagnosisf microcephaly? And are there differenteverities of microcephaly? What would

ou do if you found microcephaly in a
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www.AJOG.org Journal Club Roundtable

etus with a CHD? Is there an interven-ion? Do you just observe the patient?

amlich: I am also worried that the di-gnosis of CHD is operator-dependent,o it may be less accurate in some centershan in others. Also, it may not be de-ected at the same gestational age in allabies.

ilkins: From the ultrasound view-oint, I will tell you that these 2 diag-oses are among the least accurate andost problematic to make prenatally.he prenatal diagnosis of microcephaly

s generally made with a head circumfer-nce that is 3-5 standard deviations be-ow the mean, giving a total incidence of-3%. In this article, the incidence in theontrol group was 8%, which includedar more babies than that. Even with thattandard, it is easy to miss or over-diag-ose microcephaly. CHDs are difficult toiagnose and even more difficult to com-letely characterize prenatally. In otherords, it is easier to say that there is an

bnormality than to provide a precise di-gnosis. In terms of the prospective triale might want, this means that a case

ould easily be misclassified antenatally.e may correctly find a CHD, but incor-

ectly classify it as a coarctation, for ex-mple. So diagnosis of microcephaly andHD are complicated.ilkins: Based on their findings, how

o the authors suggest that this mighthange your obstetric management ofomen whose fetuses have a cardiac

esion?ato: The authors suggest that theseomen are possible candidates for ear-

ier monitoring for evidence of cerebralypoxia in the fetus. Specifically, theyuggest nonstress tests (NSTs), biophys-cal profiles, and MCA Doppler studies,ossibly starting as early as 28 weeks ifot earlier. They also suggest frequentiometry at 2-3 week intervals to assesetal head growth. Finally, they wouldonsider early delivery after confirmingung maturity.

ilkins: Is there any downside toesting these fetuses?

ato: The downside is, when you get anbnormal result, you have to act on it,hich would mean possible early deliv-

ry. On occasion, that will entail false-

ositives with a possibly unnecessary t

arly delivery. However, even in casesith clearly abnormal results, there areroblems with early delivery in fetusesith CHDs. They would not have

chieved maximum weight, and theirearts would not have reached the opti-al size to facilitate neonatal surgery,

hereby preventing them from achievinghe most benefit from surgery. Thisould lead to increased morbidity andortality in the newborn.ilkins: I’m not convinced that these

atients have abnormal biophysical pa-ameters and that cardiotocography andiophysical profiles would pick up thisroblem.

ilkins: What might be the bestntenatal testing in this population?ow important is Doppler assessment,

nd how might it be used with moretandard antenatal evaluation?olon: Based on these studies, MCAoppler may be useful in monitoring ce-

ebral hypoxia. Reduced oxygen contentn the blood, caused by intracardiac mix-ng, retrograde flow from the right heart,nd lesions that reduce blood flow to therain, spurs changes that can be moni-ored by MCA Doppler. Changes inoppler ultrasonography occur when

erebral blood vessels dilate in responseo increased blood flow volume and ox-gen delivery. It may be a helpful adjuncto our usual antenatal surveillance withSTs and biophysical profiles. These fe-

uses could be monitored by obtaining aaseline MCA Doppler and subsequenteasurements to note changes indica-

ive of worsening hypoxia. This mightelp decide timing of delivery for these

etuses so that we can improve neurode-elopmental outcomes; at this point,hat is conjecture.

ilkins: Are we convinced thatooking for fetal growth, andpecifically, head growth, is somethinge might do clinically, starting rightow, based on this paper? Is anyoneonvinced of that?olon: We do know that fetuses withHDs are at increased risk for growthroblems. So, most of us perform serialltrasounds to monitor the heart abnor-ality and assess fetal weight. I think at

his point, I would start antenatal testing f

JULY 2009 Am

f the fetus has obvious IUGR or anyroblems with growth.

ilkins: If tomorrow, we have aatient whose fetus had no IUGR butid have a small head with a CHD,hat information should we provide,nd what care should we offer?ato: I think it would depend on gesta-

ional age; I don’t know if I am convincedhat intervention at an early gestational ageould benefit the fetus in the long term.or example, if surgical correction is a pos-ibility, I am concerned that early delivery

ight make them poor candidates for sur-ery. We may be causing more harm thanood by delivering them early.

ilkins: Would you start NSTs onhat patient without IUGRruz: I think if you start NSTs at an earlyestational age, you may end up with anarly delivery and compromise the neo-ate’s chance of having cardiac surgeryt a more advanced age. I don’t see a roleor NSTs if you don’t want to deliver aetus early.

ato: Unless it was otherwise indicated,don’t think I would recommend NSTsither.

ilkins: What do you think of theuthors’ suggestion that once theatient gets a little further along, youo an amniocentesis for lung maturitynd deliver?amlich: How do you know that what-

ver damage was going to be done hasn’tlready been done by that time anyway?

ilkins: Well, that is a good point.ut, nonetheless, would you let theatient go to 40 weeksm, or even 41eeks, or would you use this as anrgument to deliver her a little earlier,iven the possibility that there isngoing damage?olon: I think if I saw microcephaly and

he fetus was 35-36 weeks, I would prob-bly do an amniocentesis, and if theungs were mature, I would deliver.

ilkins: How reassured are we thatabies in this study that did not haveicrocephaly are fine? In other words,

o you think this is a continuum, oro you think this is an insult thatome babies have and others don’t?ato: I don’t think we know. Based on

his study, we don’t have that answer; a

ollow-up study needs to be done before

erican Journal of Obstetrics & Gynecology e11

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e establish this as a standard of care. Weeed to presume that microcephaly is aeliable marker for neurologic impair-ent in this population and study the

ventual outcome for these fetuses. f

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