Materials and Methods

We performed a secondary analysis of women with untreated mild gestational glucose intolerance. Participants were women who were assigned randomly to no treatment in the previously reported Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network multicenter randomized trial of treatment for mild GDM and women in the associated observational cohort, which comprised women with a 50-g glucose screen of ≥135 mg/dL who did not meet criteria for GDM.

All the women who participated in the study provided written informed consent. The study was approved by the human subjects committee at each participating center.

To be eligible for participation in the primary study, women had to be between 24 weeks 0 days and 30 weeks 6 days’ gestation and have a 50-g glucose loading test screen between 135 and 199 mg/dL. Eligible women underwent diagnostic testing with a 100-g 3-hour OGTT. Women with normal fasting values (<95 mg/dL), but at least 2 OGTT values that exceeded established thresholds (1 hour, 180 mg/dL; 2 hours, 155 mg/dL; 3 hours, 140 mg/dL), were assigned randomly to treatment for mild GDM or usual care. In addition, women with normal OGTT results were followed in an observational cohort. Participants in the observational cohort were frequency matched at each participating center to the GDM group by BMI < or ≥27 kg/m ² and race/ethnicity. By design, providers were blinded to OGTT results for women who were randomly assigned to the usual care and observational groups; therefore, clinical care was unrelated to OGTT results. Further details of the methods of the study have been described elsewhere. Women were excluded from the primary study if they had any of the following conditions: have preexisting diabetes mellitus; had an abnormal result on a glucose screening test at <24 weeks or previous GDM; have a history of stillbirth, multifetal gestation, asthma, or chronic hypertension; receive corticosteroid therapy; have a known fetal anomaly, or likely to have imminent preterm delivery.

For the current analysis, we excluded women for whom data were missing on pregravid BMI (n = 110), which left 414 women with mild GDM who were assigned randomly to usual care and 836 who were enrolled in the observational cohort. We used maternal pregravid weight and measured height to calculate pregravid BMI (kilograms per square meter). Maternal weight was abstracted from the prenatal record or obtained by patient report; height was measured at the time of the 3-hour OGTT.

The primary outcome of the parent study was a composite outcome of perinatal death, hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia, or birth trauma. Gestational hypertension was defined as systolic blood pressure of ≥140 mm Hg or diastolic blood pressure of ≥90 mm Hg on 2 occasions at least 4 hours apart or 1 elevated blood-pressure value that subsequently was treated with medication. Preeclampsia was defined as elevation in blood pressure, as defined for gestational hypertension, with proteinuria (≥300 mg of protein/24-hour collection or dipstick ≥2, if 24-hour collection not available) or with aspartate aminotransferase level at ≥70 U/L or platelet count <100,000/L. Birthweight z-score was calculated with US singleton birthweight percentiles for gestational age from 1994-1996. Large for gestational age (LGA) birthweight was defined as >90% for gestational age; small for gestational age (SGA) was defined as birthweight <10% for gestational age. To estimate neonatal fat mass, trained research staff measured the infant’s length, head and upper mid-arm circumferences, and flank skinfold shortly after the infant’s birth.

We used Spearman correlation coefficient to measure the association between 3-hour OGTT parameters and maternal pregravid BMI. We then used logistic regression to measure the association between maternal pregravid BMI, OGTT results, and the following pregnancy outcomes: composite neonatal outcome, gestational hypertension or preeclampsia, preeclampsia alone, LGA, and SGA. We used linear regression further to model the association between maternal pregravid BMI, OGTT results and birthweight z-score, and neonatal fat mass. All regression models included parity, maternal age and race/ethnicity, maternal pregravid BMI, and all 4 OGTT values. To illustrate the magnitude of differences that were associated with a range of maternal pregravid BMI, we present predicted probabilities ( Figure 1 ) and z-scores and fat mass ( figure 2 ) for each outcome as a function of maternal BMI for a hypothetic multiparous white woman with population mean values for age (27.9 years) and for the OGTT (fasting, 85.3; 1 hour, 166.5; 2 hours, 144.3; 3 hours, 117.1). The Shieh-O’Brien approximation was used for power calculations. All the statistical analyses were performed with SAS statistical software (SAS Institute, Cary, NC) and R ( www.r-project.org ).

Predicted probability of primary outcome, gHTN, preeclampsia, SMA, and LGA, by prepregnancy maternal BMI

Predicted probabilities of pregnancy outcome are given for a hypothetical multiparous white woman with mean values for age (27.9) and oral glucose tolerance test values (fasting, 85.3 mg/dL; 1 hour, 166.5 mg/dL; 2 hours, 144.3 mg/dL; 3 hours, 117.1 mg/dL). Models include parity, maternal age, race/ethnicity, maternal pregravid body mass index, and all 4 oral glucose tolerance test values.

BMI, body mass index; gHTN, gestational hypertension; LGA , large for gestational age; SMA , small for gestational age.

Stuebe. BMI, OGTT, and pregnancy outcome. Am J Obstet Gynecol 2012.

Predicted birthweight z-score and fat mass by prepregnancy maternal BMI

Predicted birthweight z-score and neonatal fat mass are given for a hypothetical multiparous white woman with mean values for age (27.9) and oral glucose tolerance test values (fasting, 85.3 mg/dL; 1 hour, 166.5 mg/dL; 2 hours, 144.3 mg/dL; 3 hours, 117.1 mg/dL). Models include parity, maternal age, race/ethnicity, maternal pregravid body mass index, and all 4 oral glucose tolerance test values.

BMI, body mass index.

Stuebe. BMI, OGTT, and pregnancy outcome. Am J Obstet Gynecol 2012.

Results

Of the 1250 women who were eligible for inclusion in our analysis, most were Hispanic (54.2%). The mean maternal age was 27.9 years, and 34% of the women were nulliparous ( Table 1 ).

Maternal pregravid BMI correlated with fasting 3-hour OGTT results (r = 0.16; P < .001). BMI was also associated with the 1-hour value on the 3-hour OGTT and inversely associated with 3-hour value. We found correlations among all 4 3-hour OGTT parameters (all P ≤ .005), with the strongest correlations among post-load values ( Table 2 ).

In logistic regression analyses including both maternal pregravid BMI and 3-hour OGTT parameters, we found that maternal BMI was predictive of outcome independent of OGTT ( Table 3 ). Both maternal BMI and 3-hour OGTT were associated positively with the composite outcome of gestational hypertension or preeclampsia (odds ratio [OR] per 5 BMI units, 1.29; 95% confidence interval [CI], 1.10–1.51; OR per 10 mg/dL, 3-hour glucose, 1.08; 95% CI, 1.01–1.17). Maternal pregravid BMI was associated positively with LGA birthweight (OR per 5 BMI units, 1.21; 95% CI, 1.03–1.41) and associated negatively with SGA birthweight (OR per 5 BMI units, 0.77; 95% CI, 0.60–0.96). We found no statistically significant associations between maternal BMI or 3-hour OGTT parameters and preeclampsia or composite neonatal outcome. Maternal BMI was associated strongly with both birthweight z-score and neonatal fat mass. We further found that fasting glucose and 2-hour glucose values were associated with greater birthweight z-score and that fasting glucose values were associated with greater fat mass. Predicted probabilities of gestational hypertension, preeclampsia, LGA, SGA, and birthweight z-score and fat mass for a white multiparous mother aged 27.9 years with mean OGTT results are presented in Figures 1 and 2 .

TABLE 3

Association between pregravid body mass index, oral glucose tolerance test parameters, and pregnancy outcomes

Outcome	Pregravid body mass index, per 5 units	Oral glucose tolerance test, per 10 mg/dL
		Fasting	1-hr	2-hr	3-hr
Gestational hypertension/preeclampsia a	1.29 (1.10–1.51) b	1.04 (0.75–1.46)	1.06 (0.97–1.16)	1.01 (0.92–1.11)	1.08 (1.01–1.17) b
Large for gestational age a	1.21 (1.03–1.41) b	1.21 (0.88–1.68)	1.01 (0.93–1.10)	1.09 (1.00–1.19)	1.00 (0.93–1.07)
Small for gestational age a	0.77 (0.60–0.96) b	0.85 (0.58–1.24)	0.97 (0.89–1.07)	0.99 (0.89–1.10)	0.98 (0.90–1.07)
Preeclampsia a	1.13 (0.88–1.42)	1.03 (0.64–1.70)	1.04 (0.91–1.18)	1.04 (0.91–1.19)	1.01 (0.92–1.13)
Composite outcome a	1.11 (0.99–1.25)	1.20 (0.97–1.50)	1.03 (0.97–1.09)	1.01 (0.96–1.08)	1.02 (0.97–1.07)
Birthweight z-score c	0.08 (0.04–0.12) b	0.08 (0.003–0.15) b	0.004 (−0.02 to 0.02)	0.03 (0.01–0.05) b	−0.0008 (−0.02 to 0.02)
Fat mass in grams c	23.78 (12.19–35.38) b	23.34 (0.86–45.81) b	−1.78 (−7.50 to 3.94)	5.07 (–1.01 to 11.16)	3.57 (−1.39 to 8.53)

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