Maternal obesity and morbid obesity: The risk for birth defects in the offspring

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  • Maternal Obesity and Morbid Obesity:the Risk for Birth Defects in the Offspring

    Marie I. Blomberg1*y and Bengt Kallen21Division of Obstetrics and Gynaecology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences,

    University of Linkoping, Linkoping, Sweden2Tornblad Institute, University of Lund, Lund, Sweden

    Received 13 May 2009; Revised 22 June 2009; Accepted 24 June 2009

    BACKGROUND: The objective of this study was to assess, in a large data set from Swedish Medical HealthRegistries, whether maternal obesity and maternal morbid obesity were associated with an increased risk forvarious structural birth defects. METHODS: The study population consisted of 1,049,582 infants born in Swe-den from January 1, 1995, through December 31, 2007, with known maternal weight and height data.Women were grouped in six categories of body mass index (BMI) according to World Health Organizationclassication. Infants with congenital birth defects were identied from three sources: the Swedish MedicalBirth Registry, the Register of Birth Defects, and the National Patient Register. Maternal age, parity, smoking,and year of birth were thought to be potential confounders and were included as covariates in the adjustedodds ratio analyses. RESULTS: Ten percent of the study population was obese. Morbid obesity (BMI 40)occurred in 0.7%. The prevalence of congenital malformations was 4.7%, and the prevalence of relativelysevere malformations was 3.2%. Maternal prepregnancy morbid obesity was associated with neural tubedefects OR 4.08 (95% CI 1.877.75), cardiac defects OR 1.49 (95% CI 1.241.80), and orofacial clefts OR 1.90(95% CI 1.272.86). Maternal obesity (BMI 30) signicantly increased the risk of hydrocephaly, anal atresia,hypospadias, cystic kidney, pes equinovarus, omphalocele, and diaphragmatic hernia. CONCLUSION: Therisk for a morbidly obese pregnant woman to have an infant with a congenital birth defect is small, but forsociety the association is important in the light of the ongoing obesity epidemic. Birth Defects Research (PartA) 88:3540, 2010. 2009 Wiley-Liss, Inc.

    Key words: obesity; birth defects; cardiac defects; neural tube defects; orofacial clefts


    Maternal obesity is associated with an increased risk ofa range of structural birth defects. The association ismost pronounced for neural tube defects (Waller et al.,1994; Shaw et al., 1996; Werler et al., 1996; Kallen, 1998;Anderson et al., 2005; Ray et al., 2005; Waller et al., 2007;Rasmussen et al., 2008), cardiac defects (Moore et al.,2000; Shaw et al., 2000; Watkins and Botto, 2001; Mikhailet al., 2002; Cedergren and Kallen, 2003; Watkins et al.,2003; Waller et al., 2007), and orofacial clefts (Watkinset al., 2003; Cedergren and Kallen, 2005; Waller et al.,2007; Villamor et al., 2008). In a recently performed meta-analysis, obese mothers compared to mothers of recom-mended body mass index (BMI) were also at increasedrisk of having infants with anorectal atresia, hydroce-phaly, or limb reduction defects (Stothard et al., 2009)The risks are likely to be small for the individual preg-nant woman, but of general concern in the light of theongoing obesity epidemic.

    There is still lack of evidence whether the associationbetween maternal prepregnancy overweight and obesityis associated with birth defects with low prevalence rates,such as kidney malformations, diaphragmatic hernia, andsevere eye and ear malformations. Insufcient numbersof cases in each study make data difcult to interpret,results from available studies are inconclusive, and thepossible association has not been investigated at all.When studying obstetric outcome, for example, pree-

    clampsia, cesarean section, large for gestational ageinfants, and stillbirths, in relation to maternal pregreg-nancy BMI, there is convincing evidence that the risk

    *Correspondence to: Marie Blomberg, Division of Obstetrics andGynaecology, Department of Clinical and Experimental Medicine, Facultyof Health Sciences, University of Linkoping, SE-581 85 Linkoping, Sweden.E-mail: marie.blomberg@lio.seyMarie I. Blomberg was formerly known as Marie Cedergren.Published online 26 August 2009 in Wiley InterScience ( 10.1002/bdra.20620

    Birth Defects Research (Part A): Clinical and Molecular Teratology 88:3540 (2010)

    2009 Wiley-Liss, Inc. Birth Defects Research (Part A) 88:3540 (2010)

  • increases with increasing maternal BMI, reaching thehighest odds ratios among morbidly obese women(Cedergren, 2004). There are a few studies evaluatingthe risk of congenital birth defects over the obesity class IIII strata, suggested by the WHO (World Health Organi-zation, 2000). A recent meta-analysis concerning maternalobesity and risk of neural tube defects included ve stud-ies describing the risk associated with severe obesity,odds ratio 3.11 (95% CI 1.755.46). For all obese mothersthe odds ratio was 1.70 (95% CI 1.342.15). The risk formothers with severe obesity was thus nearly twice ashigh as that of obese mothers, although severe obesitywas dened differently in the ve included studies(Rasmussen et al., 2008).The objective of this study was to assess, in a large

    data set from Swedish medical health registries, whethermaternal obesity and maternal morbid obesity wereassociated with an increased risk for various structuralbirth defects.


    The study population consisted of infants born in Swe-den January 1, 1995, through December 31, 2007. Theywere identied using the Swedish Medical Birth Registry(National Board of Health and Welfare, 2003). Medicaland other data on almost all (9899%) deliveries inSweden are listed in the register, which also includesstillbirths after 28 weeks of gestation. It is based on cop-ies of the standardized medical record forms completedat the maternity health care centers at the start of prena-tal care, usually in gestational week 1012, records fromthe delivery units, and the pediatric examination of thenewborn. The system is identical throughout the country.A description and validation of the register content isavailable (National Board of Health and Welfare, 2003).Midwives recorded pregregnancy maternal weight and

    height on a standardized form at the rst visit to the ma-ternity health care center. Ninety percent of women whowill give birth present themselves to the antenatal clinicduring the rst trimester of their pregnancy.Body mass index (BMI, kg/m2) was calculated from

    maternal weight and height data. Data were missing forabout 15%. Women with known BMI were grouped insix categories of BMI: underweight (

  • 40) occurred in 0.7%. The prevalence of any congenitalmalformation among mothers with known BMI was 4.7%(49,630/1,049,582), and the prevalence of relatively severemalformations was 3.2% (33,821/1,049,582). The oddsratios for any congenital malformation and the oddsratios for relatively severe malformations according tomaternal BMI are presented in Figure 1.Maternal characteristics are presented in Table 1. The

    obese mothers were slightly older, more often multipa-rous, and more often smokers than normal weightwomen.Table 2 shows the distribution of congenital malforma-

    tions among infants of women who were underweight,normal weight, overweight, or obese before pregnancy.

    No statistically signicant association between under-weight women and infant birth defects was seen,although the risks for abdominal wall defects and hydro-cephaly were increased.Maternal overweight was associated with an increased

    risk for neural tube defects, hydrocephaly, severe earmalformations, orofacial clefts, cardiac defects, pes equi-novarus, and omphalocele.Obese women had an increased risk for neural tube

    defects, hydrocephaly, cardiac defects, orofacial clefts,anal atresia, hypospadias, cystic kidney, pes equinovarus,omphalocele, and diaphragmatic hernia.There was a decreased risk for gastroschsis among

    infants of obese women of marginal statistical signi-cance and based on only ve exposed cases. None of themothers of infants with gastroschisis were of obesityclass IIIII (3.3 expected). In 33 infants with abdominalwall defects, the defect was of another nature thanomphalocele or gastroschisis or was unclassiable (if cod-ing was made with ICD-9, the specic subtypes couldnot be differentiated).Four major congenital heart defects were also analyzed.

    There were 444 infants with tetralogy of Fallot, 514 withtransposition of great vessels, 274 with hypoplastic leftheart syndrome (HLHS), and 156 with common truncus.These four major defects were together signicantly asso-ciated with maternal obesity, OR 1.31 (95% CI 1.081.58).Each heart defect was also evaluated separately in rela-tion to maternal obesity. The risk for tetralogy of Fallotamong obese women was OR 1.37 (95% CI 0.991.88), fortransposition OR 1.14 (95% CI 0.831l.58), for HLHS 1.67(95% CI 1.132.46), and for common truncus was 1.26(95% CI 0.722.21). Thus, only for HLHS the increasedOR is statistically signicant, but all ORs may well esti-mate the same common OR.In Table 3 data for obese women were divided into

    three classes (IIII) of obesity. The risk for neural tubedefects in infants of women with obesity class I wasalmost twofold increased compared to infants of womenwith a normal BMI. Infants of women with morbid obe-

    Figure 1. The odds ratios for any congenital malformation (solidline) and the odds ratios for relatively severe malformations(dashed line) according to maternal BMI. Vertical lines indicatecondence intervals.

    Table 1Maternal Characteristics

  • sity (class III) had a fourfold increased risk of neural tubedefects. The same pattern could be seen concerning therisk of orofacial clefts, a slightly increased risk amongwomen in obesity class I, and a twofold increased riskamong morbidly obese wo


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