Gestational diabetes mellitus (GDM) complicates 2–9% of pregnancies and is associated with maternal and neonatal morbidities.1–3 Because the diagnosis and treatment of GDM can improve these undesirable outcomes,4 dietary modification, self–blood-glucose monitoring, and medical therapy if necessary to achieve glycemic control have become the mainstay of pregnancy management once a diagnosis of GDM is established.1 One important aspect of this comprehensive care is intensive dietary education and monitoring and weight monitoring. Although the Institute of Medicine (IOM) has set forth guidelines for weight gain during pregnancy (see Table 1) based on maternal prepregnancy weight and height,5 the question of ideal weight gain during pregnancy continues to be under investigation.6 Additionally, it remains unclear whether these recommendations also apply to women with GDM.
In women without diabetes, it has been reported that those with low gestational weight gain are more likely to have small for gestational age (SGA) neonates and increased neonatal morbidity.7,8 Women with excessive gestational weight gain are at risk for having macrosomic infants and associated maternal and neonatal morbidity.9–11 These findings recently were validated in a population-based study in which women with normal prepregnancy body mass indexes (BMIs) who adhered to the IOM guidelines for gestational weight gain had better pregnancy outcomes.12 In contrast, women who gained above the IOM recommendations had higher odds of preeclampsia, cesarean delivery, and large for gestational age (LGA) neonates, whereas those who gained below the IOM recommendations had higher odds of SGA neonates.12 It also has been observed that only 40% of women with good pregnancy outcomes had gestational weight gain within the IOM recommendations.12
When the association between gestational weight gain and birth weight was examined by race in low-income pregnant women, the risk of SGA and LGA were different in African-American women compared with white or Latina/Hispanic women, particularly in the high or obese BMI category.12 To date, a paucity of information exists regarding the association between gestational weight gain and pregnancy outcome in women diagnosed with GDM. Because persistent hyperglycemia contributes to excess intrauterine growth and maternal obesity augments insulin resistance,12,13 the application of a clinical guideline for the low-risk population may not necessarily apply to women whose pregnancies are complicated by GDM.
Given this background, we designed a retrospective cohort study to examine the association between gestational weight gain and perinatal outcomes in women diagnosed with GDM. In particular, we aimed to estimate whether the IOM-recommended gestational weight-gain guidelines apply to women with GDM by comparing those who had weight gain within IOM guidelines with those who gained either below or above the guidelines. We examined a cohort of women diagnosed with gestational diabetes who were enrolled in the Sweet Success California Diabetes and Pregnancy Program.
MATERIALS AND METHODS
We conducted a retrospective cohort study of women with singleton pregnancies diagnosed with GDM who were enrolled in the Sweet Success California Diabetes and Pregnancy Program and delivered between January 1, 2001, and December 31, 2004. The Sweet Success California Diabetes and Pregnancy Program is as part of the Regional Perinatal Programs of California established by the Maternal, Child, and Adolescent Health Branch of the California Department of Health Services. Sweet Success is the clinical component of the California Diabetes and Pregnancy Program and provides outpatient-based comprehensive education and nutritional, psychosocial, and medical services offered by multidisciplinary teams.14 Information regarding maternal characteristics, prenatal care, delivery, neonatal outcomes, and postpartum care were collected using standardized data-collection forms. Training was provided to optimize accuracy and ensure completeness of data collection. Exclusion criteria were multifetal gestations, pregestational diabetes (type 1 or type 2), gestational age at delivery less than 20 weeks, and women with missing weight-gain information. Institutional review board approval was obtained from the Committee on Human Research at the University of California, San Francisco.
Maternal weight gain during pregnancy was calculated from patient’s self-reported prepregnancy weight and weight at the last prenatal Sweet Success visit. The median gestational age at the last Sweet Success visit was 36 weeks, and the median gestational age at delivery was 39 weeks. Maternal weight at enrollment in the Sweet Success program was also available and used to calculate gestational weight gain before enrollment (weight difference between weight at first Sweet Success visit and prepregnancy weight) and gestational weight gain postenrollment (weight difference between weight at last and weight at first Sweet Success visit). Maternal prepregnancy BMI was calculated using prepregnancy weight and height (BMI is calculated as weight (kg)/[height (m)]2). Gestational weight gain was subgrouped into three categories: weight gain below, weight gain within, and weight gain above the IOM recommendations based on the maternal prepregnancy BMI categories (low, normal, high, or obese; see Table 1). To examine the association between absolute amount of weight gain and perinatal outcomes, gestational weight gain before and after the enrollment into the Sweet Success program also was examined. Quartiles of gestational weight gain during these two periods (preenrollment and postenrollment) were established. Women were categorized based on amount of weight gain (regardless of prepregnancy BMI) into three subgroups for each preenrollment and postenrollment period: low (weight gain less than the 25th centile), average (weight gain between the 25th and 75th centile), or high (weight gain more than the 75th centile).
Maternal outcomes examined included the severity of GDM (diet-controlled or medical therapy by either insulin or oral hypoglycemic agents), primary cesarean delivery, and antenatal admissions. Neonatal outcomes examined included preterm delivery less than 37 weeks, preterm delivery less than 34 weeks, birth weight more than 4,000 g, birth weight more than 4,500 g, large for gestational age (LGA, birth weight greater than the 90th centile), small for gestational age (SGA, birth weight less than the 10th centile), and admissions to the neonatal intensive care nursery. Gestational weight gain and perinatal outcomes were compared for women who gained below, within, or above IOM-recommended guidelines. Gestational weight gain pre-Sweet Success enrollment and post-Sweet Success enrollment also was examined.
Gestational weight gain and perinatal outcomes were examined using the χ2 test. Multivariable logistic regression models were used to control for potential confounders. These included parity, maternal age, race/ethnicity, prepregnancy BMI, gestational age at which GDM was diagnosed, severity of GDM (as reflected by diet-controlled only compared with glycemic control requiring insulin or oral hypoglycemic agents), and gestational age at delivery. Women with gestational weight gain within the IOM recommendations (15–35 lb) were designated as the reference comparison group. Statistical significance was indicated by P<.05 and 95% confidence intervals (CI). Statistical analysis was performed using STATA 9.0 (StataCorp, College Station, TX).
There were 31,074 women with GDM meeting study criteria. The mean gestational age at diagnosis of GDM was 26.4±6.36 weeks, and the mean gestational age at enrollment in the Sweet Success program was 27.9±7.21 weeks. There were 10,939 (35.2%) women who had gestational weight gain below the IOM guidelines according to their prepregnancy BMI, 10,287 (33.1%) with weight gain within the guidelines, and 9,848 (31.7%) with weight gain above the guidelines. Nulliparas were more likely to have gestational weight gain above the IOM guidelines compared with multiparas (36.9% compared with 30.4%, respectively, P<.001). Women younger than 19 years at time of delivery were also more likely to gain weight above the IOM guidelines (53.1%) compared with other age groups (P<.001; Table 2). Patterns of gestational weight gain differed by race/ethnicity, with more African-American women gaining weight above guidelines and more Asian women within guidelines (Table 2). Women with a low or normal prepregnancy BMI were more likely to gain below guidelines than those in the higher BMI categories (P<.001, Table 2). Gestational age at time of GDM diagnosis was also associated with variations of weight gain such that women with an early GDM diagnosis (less than 20 weeks) were more likely to gain below guidelines (53.2%) compared with those with a late GDM diagnosis (33 weeks or more; P<.001, Table 2).
Women who had gestational weight gain above the IOM guidelines had a higher frequency of primary cesarean delivery (25.4%) compared with those who gained within (19.8%) or below (16.6%) guidelines (P<.001, Table 3). More women who gained below guidelines maintained as diet-controlled GDM, and higher weight gain was associated with antenatal admissions, although indications for hospitalization were not available (Table 3). In addition, weight gain above the guidelines was associated with higher birth weight, and weight gain below the guidelines was associated with low birth weight/SGA (P<.001, Table 3). Other perinatal outcomes associated with gestational weight gain, although statistically significant, were small in magnitude (Table 3).
In multivariable logistic regression analysis controlling for potential confounders, women who gained above the IOM guidelines had higher odds of primary cesarean delivery (aOR 1.52, 95% CI 1.26–1.83). In addition, those who gained above the guidelines had higher odds of needing medical therapy for glycemic control. They also had higher odds of preterm delivery and of having macrosomic or LGA neonates (Table 4). In contrast, women who had weight gain below the IOM guidelines were more likely to maintain as diet-controlled GDM, and were less likely to have LGA but more likely to have SGA neonates (aOR 1.39, 95% CI 1.01–1.90; Table 4). We also repeated this analysis excluding women who were diagnosed with GDM at less than 20 weeks gestation and observed similar associations as those reported for the entire cohort above (results not shown). In addition, we further stratified the study cohort based on BMI categories according to the World Health Organization (BMI less than 18.5, 18.5–24.9, 25.0–29.9, and 30 or more as low, normal, high, or obese, respectively) and examined the association between corresponding gestational weight gain and perinatal outcomes. We observed similar direction and magnitude of association between gestational weight gain and perinatal outcomes according to these BMI categories (results not shown).
To address whether the diagnosis of GDM and enrollment in the Sweet Success program altered gestational weight gain, we stratified weight gain into two categories: before and after Sweet Success enrollment. In this cohort, the mean gestational age at GDM diagnosis was 26.4 weeks and the mean gestational age of Sweet Success enrollment was 27.9 weeks–a 10-day lag between diagnosis and enrollment. The median weight gain before enrollment was 18 lb (interquartile range 9–27), and mean weight gain per week during this period was 0.64±0.54 lb. The median weight gain from enrollment until delivery was 3 lb (interquartile range 0–8), and mean weight gain per week was 0.41 lb±2.38. Thus, for gestational weight gain before Sweet Success enrollment, less than 9 lb was designated as low, 28 lb or more as high, and women who gained 9–27 lb were designated as the reference. Similarly, for gestational weight gain after Sweet Success enrollment, less than 0 lb (weight loss) was designated as low, 8 lb or more as high, and outcomes were compared with women who gained 0–8 lb. Women with low weight gain before Sweet Success enrollment had lower odds of needing medical therapy (aOR 0.74, 95% CI 0.66–0.83) and of having LGA neonates (Table 5). Those with weight gain of 28 lb or more had higher odds of medical therapy, preterm delivery, and macrosomic/LGA neonates (Table 5). Although most women gained a small amount of weight after Sweet Success enrollment, those with a low weight gain postenrollment were more likely maintain diet-controlled GDM and had lower odds of LGA. In contrast, women with weight gain of 8 lb or more postenrollment had higher odds of primary cesarean delivery (aOR 1.32, 95% CI 1.10–1.57), GDM requiring medical therapy (aOR 1.69, 95% CI 1.53–1.87), and high birth weight/LGA but lower odds of preterm delivery (Table 5). In addition, we repeated these analyses with stratification by severity of GDM (diet-controlled only compared with medical therapy required) and by parity (nulliparas compared with multiparas); we found similar trend and magnitude of associations (results not shown).
This study examined the association between gestational weight gain and perinatal outcomes in women diagnosed with gestational diabetes. We observed that women with gestational weight gain above the IOM guidelines were more likely to have a primary cesarean delivery and high birth weight, whereas women with less-than-recommended weight gain were more likely to maintain glycemic control with dietary modifications alone but had increased odds of SGA. Although information regarding indications for cesarean delivery was not available for analysis, our findings are consistent with prior studies that have reported that excessive gestational weight gain in nondiabetic or unselected populations was associated with increased risk of operative delivery, macrosomia, and worse neonatal outcomes, whereas low weight gain increased the risk of SGA.9–12
Although many of the risk factors for GDM, such as race/ethnicity, family history, and maternal age,1 are not modifiable, we observed that the severity of GDM is associated with gestational weight gain and can be modified by nutritional education, dietary changes, and exercise.15 Because gestational diabetes requiring medical therapy is associated with adverse outcomes,16 this information may be part of the counseling for women diagnosed with GDM and may be an incentive to comply with management.
One primary concern in pregnancies complicated by GDM is excessive fetal growth, which, at term, is associated with both maternal and neonatal morbidities.1 In this cohort, gestational weight gain above the IOM guidelines is associated with increased odds of high birth weight and LGA when examined in the entire cohort, by time period (pre-GDM diagnosis/Sweet Success enrollment and post-GDM diagnosis/Sweet Success enrollment), and by the severity of GDM. Besides the short term implications associated with macrosomia, it has been shown that offspring of women with GDM who were LGA at birth are at significantly increased risk of childhood metabolic syndrome (components of which include obesity, hypertension, insulin resistance/diabetes mellitus, and hyperlipidemia) as early as age 6.17 The positive association between macrosomia/LGA and excessive weight gain in women with GDM on diet control alone is suggestive that, as glycemic control affects fetal growth, maternal weight gain during pregnancy also contributes to intrauterine growth and potentially may influence long-term health outcomes in children of diabetic mothers. A recent large, multicenter cohort trial also reports that maternal hyperglycemia is associated with increased risk of primary cesarean delivery, LGA, and increased cord blood C-peptide levels indicating fetal hyperinsulinemia in a continuous fashion,18 thus underscoring the importance of euglycemia during pregnancy.
Management and treatment of gestational diabetes involve dietary modification, exercise, and self monitoring of blood glucose. Yet, little information exists regarding how diabetes education and dietary counseling potentially may alter the course of gestational weight gain in women diagnosed with GDM. In this cohort, we observed a significant reduction in both the rate of weight gain (0.64 lb/week preenrollment compared with 0.41 lb/week postenrollment) and the amount of weight gain (median 18 lbs preenrollment compared with 3 lbs postenrollment) after enrollment in the Sweet Success Program. Currently, there are no specific recommendations regarding the ideal amount of weight gain for women diagnosed with GDM. Although clinical attributes certainly play a role in the determination of an “appropriate” gestational weight gain, we found that a weight gain of 8 lb or more (or 0.76 lb/wk) after GDM diagnosis/enrollment in Sweet Success was at the 75th centile of the cohort. Because the mean gestational age at GDM diagnosis and enrollment in Sweet Success was 26.4 weeks and 27.9 weeks, respectively, it appears that women were diagnosed and enrolled in a timely fashion and that the education and care provided by clinicians as well as the Sweet Success staff may have helped to reduce gestational weight gain, thus improving outcomes.
As we examined the association between gestational weight gain and perinatal morbidity, there are limitations to our study. First, there are a number of outcomes often associated with diabetes during pregnancy that we could not examine in detail. These included indications for antenatal admissions, degree of glycemic control, details of labor/delivery, and complications often related to hyperglycemia as well as preexisting medical conditions such as chronic hypertension. Additionally, gestational weight gain was determined by prepregnancy weight, which may be subject to recall bias, and weight at last Sweet Success visit, which may not reflect maternal weight at delivery and, thus, total gestational weight gain. Because women usually gain rather than lose weight during the third trimester of pregnancy, using weight at last Sweet Success visit likely underestimates the true gestational weight gain. This misclassification likely would contribute to the effect estimates in a nondifferential fashion and bias our results toward the null. Because we consistently found that excessive weight gain is associated with undesirable outcomes, the reported association is likely valid.
As with all observational studies, our study may be prone to confounding bias. Although we used statistical techniques to control for potential confounders, there may be residual confounding which we could not observe or for which we did not control. Ideally, a randomized controlled trial would more accurately evaluate the causal association between gestational weight gain and perinatal outcomes. However, this would require assigning women to a set amount of weight gain in a random fashion, which may be challenging or nearly impossible and requires a large sample size.
Our study validates that excessive weight gain above the IOM guidelines is associated with undesirable perinatal outcomes; this applies to women with GDM. When diabetic women have weight gain above the IOM guidelines, they have higher risk of macrosomia and are more likely to require medical therapy for glycemic control as well as cesarean delivery and preterm delivery. In contrast, women with weight gain below the IOM guidelines have lower overall cesarean delivery and LGA and are more likely to maintain as diet-controlled GDM, although the risk of SGA is slightly higher. We speculate that women with GDM may not require the same amount of weight gain as women without GDM.
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