The effect of maternal obesity on pregnancy outcomes in women

with gestational diabetes

ASHLEY S. ROMAN1, ANDREI REBARBER1, NATHAN S. FOX1, CHAD K. KLAUSER1, NIKI ISTWAN2,

DEBBIE RHEA2, & DANIEL SALTZMAN1

1Maternal Fetal Medicine Associates, PLLC, New York, NY, USA, and 2Alere Women’s and Children’s Health,

Clinical Research, Atlanta, GA, USA

(Received 29 June 2010; revised 1 September 2010; accepted 3 September 2010)

Objective. To examine the impact of maternal obesity on maternal and neonatal outcomes in pregnancies complicated withgestational diabetes mellitus (GDM).

Methods. Women with singleton pregnancies and GDM enrolled in an outpatient GDM education, surveillance andmanagement program were identified. Maternal and neonatal pregnancy outcomes were compared for obese (pre-pregnancyBMI� 30 kg/m2) and non-obese (pre-pregnancy BMI5 30 kg/m2) women and for women across five increasing pre-pregnancy BMI categories.

Results. A total of 3798 patients were identified. Maternal obesity was significantly associated with the need for oralhypoglycemic agents or insulin, development of pregnancy-related hypertension, interventional delivery, and cesareandelivery. Adverse neonatal outcomes were also significantly increased including stillbirth, macrosomia, shoulder dystocia,need for NICU admission, hypoglycemia, and jaundice. When looking across five increasing BMI categories, increasingBMI was significantly associated with the same adverse maternal and neonatal outcomes.

Conclusion. In women with GDM, increasing maternal BMI is significantly associated with worse maternal and neonataloutcomes.

Keywords: Gestational diabetes, obesity, body mass index, adverse outcomes

Introduction

The prevalence of obesity among women of reproductiveage has increased dramatically over recent years. In 2007–2008, 68% of United States adults and 59.5% of women ofreproductive age met criteria for being categorized asoverweight or obese [1]. With the rising prevalence ofobesity, recent studies have highlighted the increased risksassociated with obesity in pregnancy, including increasedrisks of cesarean delivery, stillbirth, hypertensive disordersof pregnancy, fetal structural malformations, and gesta-tional diabetes; however, controversy remains over optimalmanagement of the pre-gravid obese women duringpregnancy, including recommendations for weight gainduring pregnancy [2].

Gestational diabetes mellitus (GDM) which is defined asglucose intolerance during pregnancy affects approxi-mately 135,000 women or 4% of all pregnancies per yearin the United States [3]. Pregnancies complicated withGDM are also at increased risk for many maternal and fetalcomplications, including cesarean delivery, macrosomia,neonatal hypoglycemia, stillbirth, and neonatal intensivecare unit (NICU) admission [4]. The combination of pre-gravid obesity and GDM has been shown to be associatedwith an increased risk of adverse pregnancy outcomes overeither disorder alone [5,6].

The objective of this study was to examine the impactof increased maternal pre-pregnancy body mass index(BMI), including overweight, obese, and morbidlyobese categories, on maternal and neonatal outcomesin pregnancies complicated with GDM, enrolled inan outpatient GDM education and managementprogram.

Methods

The study population was identified retrospectively from alarge centralized perinatal database containing de-identi-fied clinical information collected between July 2000 andJuly 2009 from pregnant women diagnosed with GDM andenrolled in an outpatient GDM education, surveillance,and management program provided by Alere (formerlyMatria Healthcare). All women provided written consentfor outpatient services and for the later use of their de-identified personal health information for research andreporting purposes. Each patient’s healthcare providermade the diagnosis of GDM, and outpatient services wereprescribed as an adjunct to routine prenatal care. Maternalcharacteristics (including pre-pregnancy height andweight), and medical/obstetric history were collectedduring the initial referral process. A perinatal nurse

Correspondence: Ashley Roman, MD, MPH, 1245 Madison Avenue, New York, NY 10128, USA. Tel: þ1-212-722-7426. Fax: þ1-212-722-7185.

E-mail: aroman@mfmnyc.com

Presented at the 30th Annual Meeting of the Society for Maternal–Fetal Medicine. Chicago, IL, 1–6, February 2010. Poster # 0242.

The Journal of Maternal-Fetal and Neonatal Medicine, May 2011; 24(5): 723–727

ISSN 1476-7058 print/ISSN 1476-4954 online � 2011 Informa UK, Ltd.

DOI: 10.3109/14767058.2010.521871

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collected pregnancy outcomes from each patient approxi-mately 2–6 weeks after delivery.

Women carrying singleton gestations diagnosed withGDM by their healthcare provider who were enrolled inan outpatient GDM education, surveillance, and man-agement program and had documented pre-pregnancyBMI and delivery information were included in analysis.The GDM education, surveillance, and managementprogram consisted of one-on-one GDM education andcounseling with individualized plan of care regardingdiet, exercise, self-care, and blood glucose testing.Women were instructed on daily testing of blood glucoselevels with fasting and 1- or 2-h postprandial bloodglucose testing. Daily evaluation of blood glucose andketone values by a certified diabetes educator wasperformed. Reports were administered to the patient’shealthcare provider on a weekly basis or more frequentlyas needed.

Maternal pre-pregnancy BMI was calculated as weightin kilograms divided by height in meters squared.Maternal and neonatal pregnancy outcomes were com-pared for obese (BMI� 30 kg/m2) and non-obese(BMI5 30 kg/m2) women and for women across fiveincreasing pre-pregnancy BMI categories: underweight(518.5 kg/m2), normal weight (18.5–24.9 kg/m2), over-weight (25–29.9 kg/m2), obese (30–39.9 kg/m2), andmorbidly obese (� 40 kg/m2). Maternal outcomes eval-uated were need for pharmacologic treatment of GDM,cesarean delivery, and pregnancy-related hypertension(defined as gestational hypertension or preeclampsia).Neonatal outcomes evaluated included gestational age atdelivery, preterm birth, birth weight, stillbirth, number ofdays in the nursery, NICU admission, birth trauma(injury identified in the neonate attributed to mechanicalforces of birth, e.g. bruises, lacerations, hematomas,fractures), shoulder dystocia, hypoglycemia, andjaundice.

The primary outcome was composite neonatal morbiditydefined as the presence of one or more of the following:birth weight greater than 4000 g, birth trauma, shoulderdystocia, hypoglycemia, and jaundice.

Data were compared using Pearson’s chi-square, Mann–Whitney U test and Kruskal–Wallis H test statistics asindicated with two-sided p-values of 50.05 considered

statistically significant. A logistic regression model wasused to control for the independent effects of factors thatwere significant after univariate analyses.

Results

Three thousand seven hundred ninety-eight patients withGDM met criteria for inclusion in this analysis. Allpatients had health insurance (private or Medicaidcoverage) and were receiving prenatal care at enrollment.Of these patients, 2028 non-obese and 1770 obese wereidentified. Maternal obesity was significantly associatedwith higher blood glucose levels and need for increasedinterventions (Table I). Adverse maternal and neonataloutcomes were significantly increased in obese womenwhen compared with women of normal weight orunderweight (Table II). The mean gestational age atdelivery for stillborn infants was 35.9+ 5.0 weeks. Asignificant linear trend with increasing BMI was observedin rates of adverse maternal and neonatal outcomes(Table III).

The risk of composite neonatal morbidity was signifi-cantly increased with increasing BMI (Figure 1).

Logistic regression analysis was used to assess theimpact of the individual variables on composite neonatalmorbidity (Table IV). Among the variables examined inthis study, it appears that four were independently andsignificantly associated with developing at least one of thecomposite neonatal outcomes: delivery prior to 37 weeks,obesity, an FBG4109, and exposure to oral glycemicagents. Of these four, delivery prior to 37 weeks andfasting blood glucose greater than 109 had the strongestassociation with the composite outcome with an oddsratio of 1.7. Furthermore, the independent impact ofincreasing pre-pregnancy BMI was above and beyond theharmful effects of having a fasting blood glucose of 109,an indicator of glycemic control. However, the R2 value of0.046 indicates that 95% of the variation in the dependentvariable of composite neonatal outcome was not ex-plained by the variables examined in this study’s data.Therefore, there may be additional factors that have animpact on neonatal morbidity that are not accounted forin this study.

Table I. Maternal characteristics and GDM treatments.

BMI5 30 (n¼2028) Obese BMI�30 (n¼1770) p-value OR (95% CI)

Pre-pregnancy BMI (kg/m2) 24.6+3.3, 24.9 (11.5, 29.9) 37.3+6.2, 35.6 (30.0, 68.8) 50.001 –

Married 57.4% 52.4% 0.002 0.82 (0.72, 0.93)

Maternal age (years) 30.9+ 5.8, 31 (16, 51) 31.0+5.5, 31 (16, 46) 0.749

Age� 35 years 27.0% 27.6% 0.651 –

Nulliparous 36.5% 29.2% 50.001 0.72 (0.62, 0.82)

Mean fasting BG 85.3+11.9, 84.3 (50.8, 176.2) 92.1+13.9, 91.0 (59.2, 229.0) 50.001 –

499 9.3% 21.6% 50.001 2.7 (2.2, 3.3)

4109 3.1% 7.6% 50.001 2.6 (1.9, 3.7)

GA at enrollment (weeks) 30.3+4.5, 30.6 (6.6, 39.1) 29.0+ 5.9, 30.3 (6.7, 38.7) 50.001

GA at discharge (weeks) 33.4+4.1, 33.6 (11.0, 41.7) 32.4+ 5.5, 33.6 (8.7, 41.4) 50.001

Days in program 21.8+ 17.4, 19 (1, 210) 23.6+20.9, 19 (1, 182) 0.004

GDM diet only 87.7% 75.2% 50.001 0.43 (0.36, 0.51)

Medications for BG control

(insulin and/or orals)

12.3% 24.8% 50.001 2.4 (2.0, 2.8)

Insulin 7.9% 14.9% 50.001 2.0 (1.7, 2.5)

Oral agents 5.2% 11.8% 50.001 2.4 (1.9, 3.1)

Data presented as mean+SD, median (min, max) or percentage as indicated. BMI, body mass index; BG, blood glucose.

724 A. S. Roman et al.

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Discussion

As the obesity epidemic in the United States continuesunchecked, maternal obesity is increasingly recognized asan independent risk factor for adverse maternal and fetaloutcomes. The prevalence of GDM has been shown toincrease with increasing pre-pregnancy BMI, with a 4–6%prevalence for women with a BMI of 30–34.9, 6–8%prevalence with BMI of 35–39.9, and 10–12% prevalencewith BMI greater than 40 [7]. Few studies, however, haveevaluated the risks of adverse pregnancy outcomes in thesetting of both obesity and GDM.

In this study, we found that maternal obesity issignificantly associated with worse maternal and neonataloutcomes. Obese women were also more likely to requiremedication for optimal blood sugar control than women

Table II. Neonatal outcomes of women diagnosed with GDM.

BMI5 30 (n¼ 2028) Obese BMI� 30 (n¼ 1770) p-value OR (95% CI)

GA at delivery (weeks) 38.3+1.7, 38.7 (25.9, 43.3) 38.1+ 1.9, 38.4 (21.1, 44.9) 50.001 –

Delivery537 weeks 14.6% 18.3% 0.002 1.3 (1.1, 1.6)

Late PTB (34–36 weeks) 12.5% 15.3% 0.013 1.3 (1.0, 1.5)

Pregnancy-related HTN 9.6% 24.4% 50.001 3.0 (2.5, 3.7)

Cesarean delivery 39.3% 52.9% 50.001 1.7 (1.5, 2.0)

Birth weight (g) 3214+525, 3232 (964, 5091) 3360+ 623, 3374 (514, 5642) 50.001 –

Birth weight44000 g 5.7% 12.8% 50.001 2.4 (1.9, 3.0)

Stillbirth 2 (0.1%) 9 (0.5%) 0.019 5.2 (1.1, 24.0)

Nursery days 3.3+4.1, 2 (1, 58) 4.0+ 7.1, 3 (1, 160) 50.001 –

NICU admission 11.0% 14.2% 0.003 1.3 (1.1, 1.6)

Birth trauma 0.2% 0.2% 0.847 1.1 (0.3, 4.6)

Shoulder dystocia 1 (0.0%) 6 (0.3%) 0.038 6.9 (0.8, 57.3)

Hypoglycemia 4.1% 5.9% 0.009 1.5 (1.1, 2.0)

Jaundice 13.6% 17.1% 0.002 1.3 (1.1, 1.6)

Data presented as mean+SD, median (min, max) or percentage as indicated. GA, gestational age; PTB, preterm birth; HTN,

hypertension.

Table III. Maternal and neonatal outcomes by advancing pre-pregnancy BMI.

Underweight,

518.5 (n¼66)

Normal,

18.5–24.9

(n¼958)

Overweight,

25–29.9

(n¼ 1004)

Obese, 30–40

(n¼1294)

Morbidly

obese,440

(n¼ 476) p-value

Developed pregnancy-

related HTN

4.5% 7.4% 12.0%* 21.7%* 31.5%* 50.001{{

Cesarean delivery 33.3% 36.3% 42.6%* 50.0%* 60.9%* 50.001{{

Birth weight (g) 2984+548,

2948

(1616, 4000)

3163+515,

3175

(964, 5091)

3279+525,

3260

(992, 4819)*

3343+ 615,

3364

(624, 5318)*

3406+ 645,

3455

(514, 5641)

50.001

Birth weight44000gms 0 4.6% 7.2% 12.4%* 13.7% 50.001{{

Stillbirth 0 0.1% 0.1% 0.6% 0.2% 0.110{, 0.099{

Nursery days 3.6+ 3.5, 2

(1, 19)

3.2+ 3.5, 2

(1, 45)

3.5+4.7, 2

(1, 58)

3.9+ 6.3, 3

(1, 135)*

4.1+8.9, 3

(1, 160)

50.001

NICU admission 12.1% 9.8% 12.1% 13.9% 14.9% 0.022{, 0.001{

Birth trauma 0 0.2% 0.2% 0.2% 0.4% 0.856{, 0.593{

Shoulder dystocia 0 0.1% 0 0.2% 0.8% 0.009{, 0.012{

Hypoglycemia 0 4.3% 4.2% 5.2% 8.0% 0.005{, 0.001{

Jaundice 13.6% 13.3% 13.8% 15.8% 20.8% 0.003{, 50.001{

Data presented as mean+SD, median (min, max) or percentage as indicated.

*p-value 50.0125 vs. previous BMI group (adjusted for multiple comparisons).

{Pearson’s chi-square.

{Chi-square for linear trend.

Figure 1. Composite neonatal morbidity. Presence of one or more

of the following: birth weight 44000 g, birth trauma, shoulder

dystocia, hypoglycemia, or jaundice (p50.001).

Effect of maternal obesity on pregnancy outcomes 725

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with a BMI less than 30. Furthermore, the risks of bothmaternal and neonatal morbidity increase significantly withincreasing pre-pregnancy BMI, particularly the risks ofpregnancy-related hypertension, cesarean delivery, andcomposite neonatal morbidity. The highest risks of theseoutcomes were seen in women with morbid obesity(BMI440), but even women with a BMI in the overweightrange (BMI 25–29.9) had higher risks of cesarean deliveryand pregnancy-related hypertension than women with anormal BMI.

These findings are consistent with prior studies [5,6]that found the combination of obesity and GDM isassociated with an increased risk of adverse pregnancyoutcomes and pregnancy-related hypertension. Unlikeprevious studies, however, we found that obese womenhad significantly higher fasting blood sugar results, weremore likely to require medication for blood sugar manage-ment, and were more likely to require cesarean delivery. Inour study, this increased risk of cesarean delivery was notonly just seen in obese women but also in women in theoverweight category. These findings are consistent withprior studies on the impact of obesity on pregnancy [8].Additionally, they are medically plausible as higher insulinresistance as seen in the setting of obesity has been shownto be related to hypertensive disorders.

Our study is unique in that it is the first study of womenwith GDM that stratifies outcomes not just by the presenceor absence of obesity, but by degree of obesity as defined byBMI and is the first to examine the effect of morbid obesityon pregnancy outcomes. The advantage to this approach isthat our findings allow for more targeted patient counsel-ing. The other strengths of our study include the largesample size, the detailed short-term neonatal outcomes,and the inclusion of underweight women as a comparisongroup. Aside from its retrospective design, the primaryweakness of this study is that data were obtained frompatient report over the phone and were not verified byreviewing each individual patient’s medical record. Ad-ditionally, this study evaluated short-term neonatal out-comes only. Some data indicate that fetal exposure tomaternal obesity and diabetes do not have only short termeffects on offspring but also have life-long consequences,including an increased risk of obesity and type 2 diabetes inchildhood and adolescence [9]. Both human and animaldata suggest that the risk of childhood diabetes in theseoffspring cannot be explained by the child’s obesity aloneand may also be mediated via beta-cell dysfunction

[10–12]. However, within the confines of this study, wewere unable to assess long-term effects of obesityand GDM.

Finally, it should be noted that, while the logisticregression model used in this study is a good fit for thestudy data (goodness-of-fit test p¼ 0.307), 95% of thevariation in the dependent variable of composite neonataloutcome is not explained by the variables examined in thisstudy’s data. Therefore, more studies are needed to assessother variables not collected in this study that may haveadditional impact on neonatal outcome.

In conclusion, our study indicates that women with GDMwho have a pre-pregnancy BMI of �30 are at increased riskof a number of adverse maternal and neonatal outcomes.Moreover, even women in the overweight category (BMI 25–29.9) who are diagnosed with GDM are at increased risk formaternal complications such as cesarean delivery andpregnancy-related hypertension. Among women who areobese, the risk of adverse outcomes increases with increasingBMI, with women who are classified as morbidly obese(BMI� 40) at the highest risk of maternal and neonatalmorbidities. This information is particularly useful in coun-seling obese women regarding the cumulative risks asso-ciated with both pre-pregnancy obesity and gestationaldiabetes. It also supports the goal of normalizing or evensimply reducing BMI within the obese range prior toconceiving to reduce the risk of adverse pregnancy outcomes.

Acknowledgments

Niki Istwan and Debbie Rhea are employees of Alere, thecompany that provided the diabetic services described inthe manuscript and compiled the database used for analysisin the manuscript. Daniel Saltzman and Andrei Rebarberare members of the Alere speakers’ bureau and have servedas consultants for Alere. Chad Klauser has been a memberof Alere’s speakers’ bureau in the past but is not currently amember. Nathan Fox and Ashley Roman report nodeclarations of interest.

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Table IV. Logistic regression model results assessing composite

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Parameter p-value OR (95% CI)

Delivery537 weeks 50.001 1.7 (1.4, 2.1)

Pre-pregnancy BMI 50.001 1.2 (1.1, 1.3)

FBG4109 0.005 1.7 (1.2, 2.4)

Oral glycemic agent 0.024 1.3 (1.0, 1.7)

Cesarean delivery 0.117 1.1 (1.0, 1.3)

Insulin 0.198 1.2 (0.9, 1.5)

Pregnancy-related HTN 0.403 1.1 (0.9, 1.3)

FBG499 0.777 1.0 (0.8, 1.3)

BMI, body mass index; FBG, fasting blood glucose; HTN,

hypertension. The pre-pregnancy BMI parameter compares the

following groups: underweight (518.5); normal (18.5–24.9),

overweight (25–29.9), obese (30–40), morbidly obese (440).

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Effect of maternal obesity on pregnancy outcomes 727

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