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Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e318256cf1a
Original Research

Excessive Early Gestational Weight Gain and Risk of Gestational Diabetes Mellitus in Nulliparous Women

Carreno, Carlos A. MD; Clifton, Rebecca G. PhD; Hauth, John C. MD; Myatt, Leslie PhD; Roberts, James M. MD; Spong, Catherine Y. MD; Varner, Michael W. MD; Thorp, John M. Jr MD; Mercer, Brian M. MD; Peaceman, Alan M. MD; Ramin, Susan M. MD; Carpenter, Marshall W. MD; Sciscione, Anthony DO; Tolosa, Jorge E. MD, MSCE; Sorokin, Yoram MD; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network

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Author Information

From the Department of Obstetrics and Gynecology of the University of Texas Health Science Center at Houston, Houston, Texas; the University of Alabama at Birmingham, Birmingham, Alabama; the University of Cincinnati, Cincinnati, Ohio; the University of Pittsburgh, Pittsburgh, Pennsylvania; the University of Utah, Salt Lake City, Utah; the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio; Northwestern University, Chicago, Illinois; the University of Texas Health Science Center at Houston, Houston, Texas; Brown University, Providence, Rhode Island; Drexel University, Philadelphia, Pennsylvania; Oregon Health & Science University, Portland, Oregon; the University of Texas Medical Branch, Galveston, Texas; Wayne State University, Detroit, Michigan; The George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

* For a list of other members of the NICHD MFMU, see the Appendix online at http://links.lww.com/AOG/A301.

Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917, and HD36801); the National Heart, Lung, and Blood Institute; and the National Center for Research Resources (M01 RR00080, UL1 RR024153, UL1 RR024989). Its contents do not necessarily represent the official view of NICHD, National Heart, Lung and Blood Institute, National Center for Research Resources, or the National Institutes of Health.

The authors thank Elizabeth Thom, PhD, for protocol development, data management, and statistical analysis; Sabine Bousleiman, RNC, MSN, and Margaret Cotroneo, RN, for protocol development and coordination between clinical research centers; Kenneth J. Leveno and Gail D. Pearson, MD, ScD, for protocol development and oversight; and Sean Blackwell, MD, for manuscript oversight.

Presented as a poster at the at the 31st Annual Meeting of the Society for Maternal-Fetal Medicine, February 7–12, 2011, San Francisco, California.

Dr. Spong, Associate Editor of Obstetrics & Gynecology, was not involved in the review or decision to publish this article.

Corresponding author: Carlos A. Carreno, MD, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at Houston, 6431 Fannin Street, Suite 3.262, Houston, TX 77030; e-mail: carlos.carreno@uth.tmc.edu.

Financial Disclosure The authors did not report any potential conflicts of interest.

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Abstract

OBJECTIVE: To estimate whether there is an association between excessive early gestational weight gain and the development of gestational diabetes mellitus (GDM) and excessive fetal growth.

METHODS: This is a secondary analysis of a randomized controlled trial of vitamins C and E in nulliparous low-risk women. Maternal weight gain from prepregnancy (self-reported) to 15–18 weeks of gestation was measured, and expected gestational weight gain was determined using the Institute of Medicine 2009 guidelines for each prepregnancy body mass index category. Excessive early gestational weight gain was defined as gestational weight gain greater than the upper range of the Institute of Medicine guidelines. Rates of GDM, birth weight greater than 4,000 g, and large for gestational age (LGA, birth weight 90th percentile or higher) were calculated and compared between women with excessive early gestational weight gain and early nonexcessive gestational weight gain (within or below Institute of Medicine guidelines).

RESULTS: A total of 7,985 women were studied. Excessive early gestational weight gain occurred in 47.5% of women. Ninety-three percent of women with excessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines. In contrast, only 55% of women with nonexcessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines (P<.001). Rates of GDM, LGA, and birth weight greater than 4,000 g were higher in women with excessive early gestational weight gain.

CONCLUSION: In our population, excessive early gestational weight gain occurred in 93% of women who had total gestational weight gain greater than the Institute of Medicine guidelines. In low-risk nulliparous women, excessive early gestational weight gain is associated with the development of GDM and excessive fetal growth.

LEVEL OF EVIDENCE: II

Gestational weight gain occurs as a result of an increase in maternal body fat and water and consists of 30% maternal fat accumulation. Maternal weight gain varies by trimester but early in pregnancy is disproportionately fat. The second half of pregnancy is characterized by progressive insulin resistance,1,2 and maternal fat accumulation appears to influence subsequent maternal insulin resistance.2 The pattern of gestational weight gain is higher in the second trimester at a rate of 0.563 kg per week and birth weight is strongly correlated with weight gain during that period.3

Abnormal or excessive gestational weight gain is a strong predictor of pregnancy and long-term health outcomes for both women and infants. Herring et al in 2009 reported that the higher the gestational weight gain, the higher the odds of developing abnormal glucose tolerance in the third trimester of pregnancy (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.04–4.42).4 Maternal obesity and postpartum weight retention have also been linked to excessive gestational weight gain.5 In addition to these maternal outcomes, excessive gestational weight gain has been associated with large-for-gestational-age (LGA) neonates and excessive neonatal and infant weight.68 Margerison et al9 in 2010 using data from 4,496 births in the National Longitudinal Survey of Youth 1979 described the association between gestational weight gain and increased rates of LGA, cesarean delivery, and postpartum weight retention as well as childhood overweight. In the report, 40% of women with excessive gestational weight gain retained greater than 2.5 kg from 12 to 24 months after delivery and 29% of the children had a body mass index (BMI, calculated as weight (kg)/[height (m)]2) greater than the 85th percentile. In addition, postpartum weight retention is a strong predictor of maternal overweight and obesity a decade or more after the birth.10,11

Previous studies have suggested that excessive early gestational weight gain might be associated with an early increase in insulin resistance leading to exhaustion of the pancreatic B cell. This B cell depletion could reduce the capacity to compensate for the increasing insulin resistance of pregnancy and therefore lead to hyperinsulinemia, maternal hyperglycemia, and excessive fetal growth.2,4,1214

Identifying excessive gestational weight gain early in gestation could allow the opportunity to intervene at an earlier gestational age with behavioral modifications such as nutrition and exercise counseling, potentially decreasing the rate of adverse maternal and neonatal outcomes. Our objective is to estimate the relationship between excessive early gestational weight gain and gestational diabetes mellitus (GDM) as well as excessive fetal growth.

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MATERIALS AND METHODS

This study is a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network randomized clinical trial of vitamin C and vitamin E to prevent complications of pregnancy hypertension in nulliparous low-risk women. The study was conducted at 16 clinical centers between 2003 and 2008. Full details of the study design and primary results have been previously described.15 In brief, nulliparous women between 9 and 16 weeks of gestation were randomized to receive vitamin C (1,000 mg) and vitamin E (400 international units) compared with placebo to estimate if antioxidant supplementation early in pregnancy prevented preeclampsia in a low-risk population.

For this analysis, women were included if their height and self-reported prepregnancy weight were recorded, and weight measurements were available between 15 and 18 weeks of gestation (to assess early weight gain) and within the 2 weeks before delivery (to assess total weight gain). Women were excluded from this secondary analysis if they delivered before 20 weeks of gestation, died before delivery, had an elective or spontaneous abortion, or if their newborn was found to have a major congenital malformation. Excessive early gestational weight gain was defined as gestational weight gain greater than the upper range of Institute of Medicine 2009 guidelines for each prepregnancy BMI category (underweight, normal weight, overweight, and obese).3 Specifically, the cutoff for excessive early gestational weight gain was determined by adding a first-trimester weight gain of 4.4 pounds plus second-trimester weight gain per week of 1.3 pounds for underweight, 1.0 pounds for normal weight, 0.7 pounds for overweight, and 0.6 pounds for obese women.3

Outcomes included GDM, birth weight greater than 4,000 g, and LGA. Large for gestational age was defined as a birth weight at or above the 90th percentile using customized growth centiles.16 Rates were calculated and compared between women with excessive early gestational weight gain and early gestational weight gain within or below Institute of Medicine guidelines. Categorical variables were compared using the χ2 test and continuous variables using the Wilcoxon rank-sum test. Multivariable logistic regression was used to assess the relationship between excessive early gestational weight gain and study outcomes, adjusting for the compared with variables selected a priori: maternal age, race, smoking and treatment group (vitamins compared with placebo). Odds ratios and 95% CIs were reported. P<.05 was considered statistically significant. Analyses were performed using SAS software. This study was approved by the institutional review boards at the University of Texas Health Science Center at Houston and Children's Memorial Hermann Hospital.

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RESULTS

Of the 10,154 women who were randomized in the original trial, outcome data were available on 9,969 women. Of these, 1,984 were excluded, the majority for missing weight measurements at prepregnancy, 15–18 weeks of gestation, or within 2 weeks of delivery. The demographic and clinical characteristics of the 7,985 women are summarized in Table 1. The patient population had a high proportion of African Americans (23.9%) and Hispanics (29.8%), and 38% of the patients had governmental insurance.

Table 1
Table 1
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Overall, 47.5% of women enrolled in the study had excessive early gestational weight gain. Forty-five percent of women with an underweight prepregnancy BMI had excessive early gestational weight gain as well as 46% of normal weight, 54% of overweight, and 45% of obese women. Weight gain from prepregnancy to 15–18 weeks of gestation was higher in women with excessive early gestational weight gain compared with women with early nonexcessive gestational weight gain (median pounds [25th–75th percentile], 12 [9–17] compared with 2 [−2 to 5], P<.001). The relationship between excessive early gestational weight gain and total gestational weight gain according to Institute of Medicine guidelines is shown in Table 2. Ninety-three percent of women with excessive early gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines and 55% of women with early nonexcessive gestational weight gain had total gestational weight gain greater than Institute of Medicine guidelines (P<.001). Total weight gain was higher in women with excessive early gestational weight gain compared with women with early nonexcessive gestational weight gain (median pounds [25th–75th percentile], 43 [35–52] compared with 29 [21–36], P<.001). The sensitivity and specificity of excessive early gestational weight gain as a predictor of total weight gain greater than Institute of Medicine guidelines are 60% (95% CI 59–61%) and 87% (95% CI 85–88%).

Table 2
Table 2
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Table 3 shows the relationship between excessive early gestational weight gain and study outcomes for all women combined and then separately by prepregnancy BMI category. The prevalence of GDM in women with excessive early gestational weight gain was 4%. The sensitivity of excessive early gestational weight gain to predict GDM was 59% (95% CI 53–65%), and the specificity was 53% (95% CI 52–54%).

Table 3
Table 3
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The prevalence of LGA neonates in women with excessive early gestational weight gain was 12%. Excessive early gestational weight gain had a sensitivity of 54% (95% CI 51–58%) and specificity of 53% (95% CI 52–54%) to predict LGA neonates.

After adjusting for maternal age, smoking, race, and treatment group (vitamins compared with placebo), the odds of developing GDM were 43% higher in the excessive early gestational weight gain group (adjusted OR 1.4, 95% CI 1.1–1.9), the odds of delivering an LGA neonate were 40% higher (adjusted OR 1.4, 95% CI 1.2–1.6), and the odds of having a neonate with birth weight greater than 4,000 g were 51% higher (adjusted OR 1.5, 95% CI 1.3–1.8). In overweight women, excessive early gestational weight gain was not associated with a significant increase in the odds of developing GDM (adjusted OR 1.6, 95% CI 1.0–2.6, P=.06); however, it was associated with a significant increase in the odds of delivering an LGA neonate (adjusted OR 1.4, 95% CI 1.1–1.9, P=.02). Obese women did not demonstrate a difference between excessive early gestational weight gain and early nonexcessive gestational weight gain with regard to rates of GDM, birth weight greater than 4,000 g, or delivery of an LGA neonate.

Table 4 shows the obstetric outcomes in the different study groups. Labor was induced in 39% of the patients with excessive early gestational weight gain compared with 34% of women without excessive early gestational weight gain (OR 1.2, 95% CI 1.1–1.3). The most common primary indications for labor induction were postterm induction (25%), preeclampsia or hypertension (25%), elective induction (14%), premature rupture of membranes (13%), oligohydramnios (9%), and abnormal fetal testing (5%). Women with excessive early gestational weight gain also had an increased risk of cesarean delivery compared with women who did not have excessive early gestational weight gain (28% compared with 22%, OR 1.3, 95% CI 1.2–1.5). Mean birth weight also was higher in women with excessive early gestational weight gain compared with women who did not have excessive early gestational weight gain (P<.001).

Table 4
Table 4
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DISCUSSION

In 2009, the U.S. Institute of Medicine published revised guidelines for gestational weight gain. The goal of these guidelines is to optimize both maternal and child outcomes and to decrease the rates of both maternal postpartum and childhood obesity.17 These guidelines do not specifically address the timing of excessive weight gain during the pregnancy (early compared with late).

In this study, 48% of the women enrolled had excessive early gestational weight gain and 73% had a total weight gain greater than the 2009 Institute of Medicine recommendations. We found that 93% of women with excessive early gestational weight gain ultimately had total weight gain during the pregnancy that was greater than the 2009 Institute of Medicine recommendations.

Excessive early gestational weight gain was found to have a sensitivity of 60% and specificity of 87% for total pregnancy weight gain greater than 2009 Institute of Medicine guidelines. Early prediction of excess gestational weight gain could allow targeting of these women with behavioral and lifestyle modifications potentially leading to a decrease in total gestational weight gain.

The prevalence of GDM in our population was 4%, and excessive early gestational weight gain had a sensitivity of 59% and specificity of 53% for development of GDM. After adjusting for maternal age, smoking, race, and treatment group (vitamins compared with placebo), the rates of GDM (OR 1.4, 95% CI 1.1–1.9), LGA (OR 1.4, 95% CI 1.2–1.6), and birth weight greater than 4,000 g (OR 1.5, 95% CI 1.3–1.8) were higher in women with excessive early gestational weight gain compared with women with early nonexcessive gestational weight gain. The strongest effect of excessive early gestational weight gain was observed in women with a normal prepregnancy BMI. We speculate that normal weight women with excessive early gestational weight gain have a higher increase in the risk of developing GDM, LGA neonates, and birth weight greater than 4,000 g when compared with overweight or obese women because those patients with a higher prepregnancy BMI already have metabolic derangements and are therefore less affected by excessive weight gain.

We found 40% greater odds of delivering an LGA neonate (adjusted OR 1.4, 95% CI 1.1–1.9, P=.02) for overweight women with excessive early gestational weight gain. Various prior studies have demonstrated an association between increase in weight gain up to 20 weeks of gestation and increased birth weight. Muscati et al13 in 1996 found that for each 1-kg increase in weight gain up to gestational week 20, birth weight increased by 22 g. Brown et al14 found that weight gain during the first trimester was associated with a 31-g increase in birth weight per kilogram of maternal gestational weight gain. Another study found that for each kilogram gained by the mother in the first trimester, there was a statistically significant increase in fetal birth weight of 18 g.18

Hedderson et al2 in 2010 reported similar findings to our study. In a nested case–control study of 345 women with GDM, they found an 82% increase in the odds of developing GDM (OR 1.82, 95% CI 1.24–2.70) if the rate of weight gain in the first trimester was between 0.27 and 1.9 kg per week.

Our study differs from Herring et al4 in 2009 that found in a prospective cohort of 1,960 women a nonsignificant association between a high rate of weight gain less than 13 weeks of gestation but low midpregnancy weight gain and the risk of developing GDM (OR 1.70, 95% CI 0.98–2.94). Similar results were observed in the group that had a high rate of weight gain less than 13 weeks of gestation and high midpregnancy weight gain (OR 1.19, 95% CI 0.64–2.21). We did not take into account the rate of weight gain after 18 weeks of gestation.

This design is not without limitations and among them is that 20% of the women were excluded from the analysis for missing weight measurements at prepregnancy, 15–18 weeks of gestation, or within 2 weeks of delivery. The baseline demographic characteristics were different between the women included and the women excluded from the analysis. Also, the use of self-reported prepregnancy weight to determine gestational weight gain could result in under- or overestimating the associations found in this study.19 In addition, the gestational age cutoff of 15–18 weeks of gestation was selected because it coincided with the study visit, but this cutoff could potentially exclude women who had excessive gestational weight gain after this period and before the end of the second trimester of pregnancy. Strengths of our study include the use of prospectively collected data in 7,985 nulliparous women who enrolled in the original multicenter randomized clinical trial at less than 17 weeks of gestation and the biologic plausibility of a stronger association between gestational weight gain during the first trimester and the risk of GDM.20 In addition, patient enrollment from 16 different geographical locations makes our findings more generalizable to different populations.

A benefit of early identification of excessive gestational weight gain would be the opportunity for intervention early in pregnancy. Lifestyle modification and education trials have been conducted during pregnancy with the aim of affecting gestational weight gain and pregnancy outcome. Pregnancy has been proposed to be the ideal time to introduce lifestyle modification strategies given high maternal motivation to improving her child's health.2123 Streuling et al24 performed a meta-analysis of 12 trials using physical activity in pregnancy as the intervention arm and found a mean difference of gestational weight gain of −0.61 (95% CI −1.17 to −0.06) between the physical activity group and the control group.

In conclusion, excessive early gestational weight gain is associated with adverse pregnancy outcomes including GDM, cesarean delivery, and LGA. In particular, the largest effect of excessive early gestational weight gain was found in women with a normal prepregnancy BMI. Further study is needed to determine the efficacy of targeted interventions including behavioral modifications in this group to maintain gestational weight gain within the Institute of Medicine guidelines and ideally decrease GDM and LGA.

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