Gestational Diabetes Mellitus, Maternal Obesity, and Adiposity in Offspring

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<ul><li><p>Gestational Diabetes Mellitus, Maternal Obesity, and Adiposity in Offspring1 1 MD1, and Anny H. Xiang, PhD2</p><p>ellitus (GDM) on offspring adiposity in a</p><p>their index offspring. Maternal GDM andmothers were previously matched byited when offspring were between the</p><p>Conclusion Intrauterine exp xican American children, andthis relationship is not media ts, this study included onlyMexican Americans; thus, ethnic variations may influence the contributions of maternal GDM and maternal obesityBMI Body mass indexto offspring adiposity. (J Pediatr 2014;164:807-10).</p><p>Obesity and its associated comorbidities are major public health problems, and there is a disproportionate prevalence ofobesity in people of Hispanic origin. In 2003-2004, more than 75% of Mexican American adults were overweight orobese compared with approximately 66% of non-Hispanic white adults.1 Although a number of factors likely</p><p>contribute to the current obesity epidemic, a growing body of evidence suggests that intrauterine exposure to gestationaldiabetes mellitus (GDM) results in an increased risk for obesity later in life.2-9 However, some studies have found that thein utero effects of GDM on the body mass index (BMI) of offspring are attenuated when data are adjusted for maternal pre-pregnancy BMI.3,6 Studies also suggest that in addition to maternal obesity, postpartum factors such as breastfeeding also maymoderate the in utero effects of GDM exposure.10-12 Other factors, including race and ethnic variation, may play a role as well.Therefore, the aim of this study was to determine the effects of intrauterine exposure to GDM on offspring adiposity in a</p><p>cohort of well-characterized Mexican American mother-child pairs. We hypothesized that children exposed to GDM in uterowould have greater BMI and greater adiposity compared with nonexposed ethnicity-matched children and that the effects ofexposure to GDM would remain even after adjustments for maternal prepregnancy BMI.</p><p>Methods</p><p>Participants are the index offspring of probands who participated in our BetaGene Study, which included women with docu-mented GDM and age-, ethnicity-, postpartum BMI-, and parity-matched women with documented normal glucose levels inpregnancy. Details on the original BetaGene Cohort are described by Black et al.13 All study participants are self-reportedMexican American, as defined by at least three-quarters of grandparents of Mexican descent. Mothers were contacted by phonecalls, and mother-child pairs returned for a follow-up visit when offspring were between the ages of 5 and 16 years.Interviews and testing of offspring and mothers were conducted between 2010 and 2012 at the Clinical Trials Unit of the</p><p>University of Southern California Keck School of Medicine (Los Angeles, Cali-fornia) and at participants homes. The Institutional Review Board at the Univer-sity of Southern California Health Sciences Campus approved the study.Informed written consent and assent were obtained from parents and children,respectively, for their participation in the study.A detailedmedical history was collected by interviewswithmother-child pairs to</p><p>determine maternal prepregnancy weight and height, maternal weight gain during</p><p>From the 1Department of Medicine, Keck School ofMedicine, the University of Southern California, LosAngeles, CA; and 2Department of Research &amp; Evaluation,Kaiser Permanente Southern California, Pasadena, CA</p><p>Supported by the National Institutes of Health (K23DK092702, UL1 RR031986, KL2 RR031991), AmericanHeart Association (12CRP9430059), Robert E. and MayR. Wright Foundation, and the James H. ZumbergeFoundation. Study data were collected and managedusing the Research Electronic Data Capture (REDCap)database in collaboration with Southern California Clin-ical and Translational Science Institute. The authorsdeclare no conflicts of interest.GDM Gestational diabetes mellitusosure to GDM is associated with greater adiposity in Meted by maternal obesity. In contrast to previous reporages of 5 and 16 years. A medical history was collected, and anthropometrics were measured. Main outcomemea-sures were offspring BMI, BMI z-scores, BMI percentiles, and hip and waist circumferences.Results GDM-exposed offspring (n = 37) had greater measures of BMI (all P # .02) and greater waist and hipcircumferences (both P = .002) compared with 25 offspring of non-GDM mothers. Adjustment for offspring age,sex, Tanner stage, birth weight, months of breastfeeding, maternal prepregnancy BMI, and pregnancy weightgain attenuated the differences, but BMI z-score and BMI percentile remained significantly greater in theGDM-exposed group (P &lt; .05).Kathleen A. Page, MD , Ana Romero, MPH , Thomas A. Buchanan,</p><p>Objective To determine the effects of maternal gestational diabetes mwell-characterized cohort of Mexican American mother-child pairs.Study design This study included 62 Mexican American mothers andnormal glucose status during index pregnancy were documented, andage, body mass index (BMI), and parity. Mother-child pairs were recru0022-3476/$ - see front matter. Copyright 2014 Mosby Inc.All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.11.063</p><p>807</p></li><li><p>and likely reflect greater adiposity in the GDM-exposedoffspring.Some previous studies have found that adjustments for</p><p>maternal prepregnancy BMI attenuated associations betweenintrauterine exposure to GDM and childhood adiposity.3,6 Incontrast to these reports, we found that adjustments for self-reported maternal prepregnancy weight and maternal weightgain during pregnancy did not significantly affect our results.This result is not particularly surprising because GDM andnon-GDM mothers were matched for BMI when theyenrolled in our BetaGene Study, and BMI remained similarin the subset of the BetaGene cohort who participated inthis study. These similarities, together with the similaritiesof self-reported prepregnancy weights and weight gain dur-ing pregnancy, provide us with a high level of confidencethat maternal BMI was not the cause of intergroup differ-ences in BMI in offspring. Unlike previous reports, in the</p><p>THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 164, No. 4pregnancy, maternal smoking history during pregnancy,duration of breastfeeding, childs birth weight, and maternaland child medical problems. Pubertal development was as-sessed by child and mother report with a diagrammatic repre-sentation of Tanner staging adapted from Marshall andTanner.14</p><p>Offspring and maternal height and weight were measuredto the nearest 0.1 cm and 0.1 kg, respectively, with a portablestadiometer and medical scale. BMI was calculated as weightin kilograms divided by height in meters squared (m2). Age-and sex-specific BMI z-scores and BMI percentiles werecalculated from the Centers for Disease Control and Preven-tion growth curves. Waist and hip circumferences weremeasured in triplicate to the nearest 0.1 cm.Waist circumfer-ence was measured at the midpoint between the iliac crestand lower costal margin in the midaxillary line. Hip circum-ference was measured at the maximumwidth of the buttocks.</p><p>Statistical AnalysesBefore analyses, all data were checked for distributionalassumptions. Two-group independent t tests and Wilcoxonrank sum tests were performed to compare the maternaland offspring characteristics and anthropometrics betweenGDM and non-GDM groups. Conclusions were similar,and results are reported from the t test. Offspring BMI,BMI z-scores, BMI percentiles, waist and hip circumferences,and waist-to-hip ratios were compared between GDM-exposed and GDM-nonexposed groups. We first adjustedfor potential confounding caused by differences in offspringage, sex, and Tanner stage (as a continuous variable; model1). We then assessed the residual confounding caused bymaternal obesity by additionally adjusting for maternal pre-pregnancy BMI and weight gain during pregnancy (model 2).The impact of differences in duration of breastfeeding andbirth weight on the relationship between GDM exposureand offspring anthropometric outcomes was evaluated inmodel 3. Multiple linear regression was used for models1-3. Data were analyzed with SAS version 9.2 (SAS InstituteInc, Cary, North Carolina), with a significance level set atP &lt; .05.</p><p>Results</p><p>Sixty-two mother-child pairs participated in the study, 37with GDM and 25 without GDM (Table I). During theindex pregnancy from which the offspring were born,maternal age was 1 year lower in the GDM group.Participant-reported maternal weight before pregnancy,weight gain during pregnancy, and duration ofbreastfeeding after pregnancy were similar between groups.None of the mothers smoked during the index pregnancy.A greater fraction of infants in the GDM group were male,and that group had a marginally lower birth weight thanthe nonexposed group.At the follow-up examination, mothers in the GDM and</p><p>non-GDM groups had the same mean age and similar BMI.Six (16%) of the GDM mothers and 1 (4%) control mother808had been diagnosed with diabetes mellitus (Table II).Offspring exposed to GDM were 1.4 years older and hadsignificantly greater BMI, BMI z-scores, BMI percentiles,waist circumference, and hip circumference compared withGDM non-exposed offspring. Waist-to-hip ratio wassimilar in the 2 groups.Results of multiple regression analyses appear in Table III.</p><p>Model 1 shows that measures of adiposity were greater in theGDM-exposed offspring after we adjusted for child age, sex,and Tanner stage. Models 2 and 3 show that measures ofadiposity remained greater in the GDM-exposed offspringafter we adjusted for maternal prepregnancy weight, weightgain during pregnancy, child birth weight, and months ofbreastfeeding. Effects on waist and hip circumference wereslightly attenuated, and effects on waist-to-hip ratio morepronounced by these adjustments.</p><p>Discussion</p><p>We found that offspring of Mexican American mothers withGDM had greater BMI and waist and hip circumferencescompared with offspring of non-GDM mothers. The differ-ences were not explained by differences in maternal BMI</p><p>Table I. Characteristics of study cohort during theindex pregnancy*</p><p>Not exposedto GDM, n = 25</p><p>Exposedto GDM, n = 37</p><p>Pvalue</p><p>MothersAge, y 33.1 1.0 32.0 1.2 .48Prepregnancy BMI, kg/m2 28.3 9.5 28.4 4.0 .98Prepregnancy weight, kg 70.7 5.2 71.1 2.2 .95Weight gain during</p><p>pregnancy, kg12.9 1.6 10.5 1.1 .20</p><p>Smoking during pregnancy 0 0 n/aBreast-feeding duration, mo 7.6 0.8 6.2 0.7 .24</p><p>OffspringFemale 13 (52.0) 10 (27.0) .05Birthweight, g 3454 79 3186 113 .08</p><p>n/a, not available.*Data are presented as mean SE or n (%).Page et al</p></li><li><p>quences, including type 2 diabetes and cardiovasculardisease.17 In unadjusted analyses, we found that both waistand hip circumference were significantly greater in GDM-exposed compared with GDM-nonexposed offspring withno significant differences in waist-to-hip ratio, a marker ofgreater abdominal fat distribution. However, when weadjusted for covariates, we found that waist-to-hip ratiowas greater in GDM-exposed compared with GDM-nonexposed offspring. Thus, our findings suggest that the ef-fects of GDM exposure on body fat distribution also may beaffected by other factors, including age, sex, and maternalprepregnancy weight. Most studies, including our own,used waist and hip circumferences to estimate body fat distri-bution, and only a few studies have used magnetic resonance</p><p>Table II. Characteristics of the cohort at the time oftesting for the study*</p><p>Not exposedto GDM</p><p>Exposedto GDM</p><p>Pvalue</p><p>MothersAge, y 41 1.4 41 1.1 .83BMI, kg/m2 29.2 1.1 31.2 0.9 .14Diabetes, n (%) 1 (4) 6 (16) .23</p><p>OffspringAge, y 7.9 0.4 9.3 0.4 .02Tanner stage 1.2 0.1 1.8 0.2 .004BMI, kg/m2 16.9 0.6 20.3 0.8 .001BMI z-score 0.25 0.2 0.95 0.2 .02BMI percentile 52.5 6 73.7 5 .01Waist circumference, cm 61.3 2 71.5 2 .002</p><p>April 2014 ORIGINAL ARTICLESpresent study we included only Mexican American women,raising the possibility that there may be ethnic variations inthe contributions of maternal GDM and maternal obesityto the risk of overweight in offspring.Breastfeeding status has been shown to attenuate the</p><p>effects of GDM exposure on an offsprings risk ofobesity.10-12 Mayer-Davis et al10 reported a significantlyreduced risk of overweight in children exposed to maternaldiabetes in utero who were exclusively breastfed comparedwith those exclusively formula fed. Crume et al11 reportedthat breast-feeding for at least 6 months mitigated the impactof maternal diabetes on BMI and central fat distribution inchildren ages 6-13 years. After controlling for duration ofbreast-feeding months, we still found a significant effect ofGDM exposure on offspring adiposity. This may be attribut-able to the fact that average breast-feeding duration wassimilar in both GDM exposed and non-exposed groups,and on average, children in both groups were breast-fed for&gt;6 months duration. As with maternal BMI, the similarityof duration of breast-feeding between GDM and non-GDMmothers in our cohort strengthens our ability to quantifythe impact of GDM on offspring.A few studies have reported that exposure to GDM is asso-</p><p>Hip circumference, cm 69.8 2 79.6 2 .002Waist-to-hip ratio 0.88 0.01 0.90 0.01 .28</p><p>*Data are unadjusted mean SE.ciated with greater levels of abdominal fat,8,15,16 suggestingthat intrauterine exposure to diabetes may increase risk forvisceral adiposity, which is linked to adverse health conse-</p><p>Table III. Results of multiple linear regression analysis*</p><p>Offspring outcome</p><p>Model 1</p><p>Beta* 95% CI P value Beta</p><p>BMI, kg/m2 2.13 0.20 to 4.47 .072 1.96BMI z-score 0.66 0.01 to 1.32 .047 0.63BMI percentile 17.7 0.8 to 34.6 .041 17.1Waist, cm 6.0 0.5 to 12.6 .070 5.5Hip, cm 3.8 1.7 to 9.4 .17 3.2Waist/hip 0.03 0.003 to 0.065 .072 0.03</p><p>*Data are presented as regression coefficients (beta) associated with GDM exposure for each offspModel 1: adjusted for child age, sex, and Tanner stage.zModel 2: adjusted for covariates in model 1, maternal prepregnancy BMI, and weight gain duringxModel 3: adjusted for covariates in model 2, birth weight, and months of breastfeeding.</p><p>Gestational Diabetes Mellitus, Maternal Obesity, and Adiposity inimaging to quantitate visceral and subcutaneous fat stores inchildren exposed to maternal diabetes.15,18 Our findings pro-vide a strong rationale for more detailed phenotyping toidentify potential differences in body fat storage and distribu-tion between GDM-exposed and GDM-nonexposedoffspring.Our study has several limitations. The average age of the</p><p>GDM-exposed offspring was 1.4 years older than theaverage age of GDM-nonexposed offspring, and there was agreater percentage of females in the nonexposed group. How-ever, group differences inmeasures of BMI remained after ad-justments for these variables and for Tanner stage. Other thanGDM status, characteristics of the study cohort during the in-dex pregnancy were based on self-report, which holds the po-tential for error years later. The fact that mothers werematched for postpartum BMI at entry into the BetaGenestudy combined with the fact that...</p></li></ul>

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