Materials and Methods
The study cohort included all self-identified Hispanic women (n = 442) who entered prenatal care between January 1997 and January 1998 at Community Health and Social Services, a community-based, federally qualified health center that serves southwest Detroit. The study community is economically depressed and contains 60% of Detroit's Hispanic population. Specialty care and childbirth services were provided to the entire cohort by a large Detroit hospital. Seventy women were excluded because they changed providers or left the community before delivery (n = 61), terminated their pregnancies (n = 2), had twins (n = 4), or did not have glucose screening (n = 3). Cohort women were similar to those who were excluded from analyses in all respects except educational level, averaging 1 less year of education (8.9 versus 9.9 years). The cohort was predominantly Mexican (90%), born outside the continental United States (81%), low income (mean annual family income $9524), and uninsured (61%).
Sociodemographic characteristics, maternal and family health history, current pregnancy information, and pregravid weight were collected by interview at entry to care. Height, weight, random glucose, hemoglobin, and hematocrit were measured at the first prenatal visit. Maternal weight and blood pressure (BP) were recorded at each prenatal visit. Hemoglobin and hematocrit levels were reassessed for all women at 28 weeks. Ultrasound data, delivery date, and birth weight were abstracted from hospital medical records.
Maternal glucose tolerance was based on a standard 1-hour 50-g glucose screening test conducted on all nondiabetic pregnant women at 24–28 weeks' gestation. Women with normal screening results earlier in pregnancy were rescreened at this time. Women with glucose values of at least 140 mg/dL received a 3-hour, 100-g glucose tolerance test (GTT). Criteria for the diagnosis of GDM were based on GTT cutoff points established by the National Diabetes Data Group (105, 190, 165, and 145 mg/dL for the fasting and 1-, 2-, and 3-hour values, respectively).12 The health center used these screening and diagnostic criteria during the study period. All women with GDM were referred to the endocrinology department of the affiliated hospital for diabetes management.
Maternal body mass index (BMI) was based on self-reported pregravid weight and measured height and was calculated as kg/m2. If pregravid weight was unknown, a proxy measure was used for mothers with a weight measured within the first 10 weeks of pregnancy.13 Women who had no usable weight or height (n = 57) were excluded from analyses requiring BMI. Hypertensive disorders were defined as maternal history of chronic hypertension, diagnosis of preeclampsia, or gestational hypertension. The Institute of Medicine criteria were used to define anemia during pregnancy.14
Gestational age was established by comparing the reported date of onset of the last menstrual period (LMP) and a date estimated from ultrasound measurements. The LMP date was used to establish gestational age when the difference between the estimates was less than 8 days (n = 157; 42.2%) or when there was no usable ultrasound (n = 2; 0.5%). In all other cases, gestational age was assigned by the same physician (GHN) after review of ultrasound data. Large for gestational age (LGA) was defined as greater than the 90th percentile of birth weight for gestational age, and small for gestational age (SGA) was defined as less than the tenth percentile of birth weight for gestational age, based on all U.S. singleton live births in 1991.15
For these analyses, maternal screening glucose was used as a continuous variable and as part of a four-level categoric variable. Data for women with GDM were presented separately because reducing the risk of excessive fetal growth was a specific objective of the care they received after diagnosis. Nondiabetic women were presented in categories of less than 100 mg/dL, 100–134 mg/dL, and at least 135 mg/dL. These categories provided a convenient way to exhibit results and to facilitate comparisons of maternal characteristics and fetal growth outcomes at the low and high ends of the glucose distribution. The latter category was selected because values between 135 and 139 mg/dL would likely include women with at least some degree of glucose intolerance who did not undergo diagnostic testing or treatment for GDM.
Mothers classified into these four levels of glucose tolerance were compared for various characteristics. The significance of differences in proportions for categoric characteristics was tested using the Cochran-Armitage trend test. Significant differences in mean values of continuous variables across the levels were tested using one-way analysis of variance with a between-groups design. All pairs of means for each of the four levels were compared using Tukey studentized range test adjustment of the alpha level for multiple comparisons. Analysis of covariance was used to compare means between groups after adjustment for covariates. The assumptions of equal variances among comparison groups were tested and met using the Brown-Forsythe or the Levene test (SAS Assist, version 6.12; SAS Institute, Cary, NC).
Among nondiabetic women, multiple regression analysis was used to determine whether there was a significant linear relation between the maternal screening glucose value, used as a continuous variable, and infants' birth weights after adjustment for the other predictors. Predictors included in the regression models had biologic plausibility, a minimal number of missing values, and no evidence of significant collinearity. Multiple logistic regression analysis was used to model the relation between maternal screening glucose value and the incidence of the two measures of fetal growth (LGA and SGA) after adjusting for the same predictors that were used in the linear model. Use of this technique allowed us to evaluate the independent odds ratio (OR) associated with the maternal screening glucose value while simultaneously adjusting for other characteristics.
The distribution of glucose values in the cohort was 29.0% less than 100 mg/dL, 44.4% of 100–134 mg/dL, and 26.6% of at least 135 mg/dL (Table 1). Gestational diabetes mellitus was subsequently diagnosed in 5.1% of the cohort, leaving 21.5% of the women categorized as nondiabetic but with screening values of at least 135 mg/dL. Women with glucose levels less than 100 mg/dL had a significantly lower mean BMI than women in each of the other categories. Maternal age increased significantly with each successive screening glucose level. Women with GDM were significantly older and heavier than the rest of the cohort combined. There was no significant overall association between gestational age and glucose level, although women with GDM had slightly shorter pregnancies.
There was a significant trend toward an increasing proportion of women with hypertensive disorders as glucose level increased. Increasing glucose level was associated with a trend toward decreasing percentages of women with anemia during pregnancy. Women diagnosed with GDM were significantly more likely to have positive family histories of diabetes (42.1%) than the rest of the cohort (χ2, P = .028). The proportion of women having induced or cesarean deliveries before 39.5 weeks' gestation was significantly greater for those with GDM (44.4%) than for nondiabetic women (less than 12% in any screening glucose category).
There was a significant relation between maternal screening glucose level and mean birth weight, both before and after adjustment for gestational age and other potential covariates of fetal growth (Table 2). The lower unadjusted mean birth weight of infants of women with GDM may be attributable to earlier delivery because the effect of adjusting for gestational age was to increase mean birth weight in this group. The effect of further adjustment for BMI and other covariates was to reduce birth weights in all categories; however, this reduction was greatest among offspring of women with GDM. Infants of women whose glucose values were less than 100 mg/dL had significantly lower adjusted mean birth weights than infants of women in the other glucose categories. There was a significant trend toward an increasing percentage of LGA infants and a decreasing percentage of SGA infants as glucose level increased, particularly among nondiabetic women.
Because of the small number of women with GDM, there was insufficient power in this sample to detect a statistically significant difference between the mean birth weights of infants of GDM women and those in all possible combinations of the three screening glucose levels. However, infants of GDM women had lower adjusted mean birth weights, a lower proportion of LGA, and a greater proportion of SGA than infants of nondiabetic women whose glucose values were at least 135 mg/dL, despite the higher screening glucose levels and mean BMI of women with GDM. Almost one-quarter of the infants of nondiabetic women whose glucose levels were at least 135 mg/dL were LGA; none were SGA.
Among nondiabetic women, maternal glucose level was significantly associated with mean birth weight and the likelihood of having LGA or SGA infants, before and after adjustment for the effects of maternal age, BMI, multiparity, family history of diabetes, hypertensive disorders, and anemia during pregnancy (Table 3). Each 10-mg/dL increase in the glucose value resulted in a 30.5-g increase in mean birth weight, after adjusting for covariates. Each 10-mg/dL increase in glucose value was also associated with a 17% increase in the adjusted odds of having an LGA infant and a 31% decrease in the adjusted odds of having an SGA infant. A 10-mg/dL decrease in glucose value increased the odds of SGA by 44%. Among the variables modeled, only gestational age contributed more substantially than glucose value to the variation in mean birth weight in the study cohort. Maternal BMI and multiparity were also significantly associated with mean birth weight.
The maternal screening glucose level was independently associated with mean birth weight and the risk of LGA and SGA births in our cohort of Hispanic women. Among infants of nondiabetic women, mean birth weight and the likelihood of LGA increased, and the risk of SGA decreased, as maternal glucose category rose. Studies in non-Hispanic white and multiethnic populations have demonstrated the significant risks posed by both GDM and lesser degrees of glucose intolerance for macrosomic births.11,16–18 Our study confirms these findings in an exclusively Hispanic population. In our study, more than 20% of infants born to women whose screening glucose values were at least 135 mg/dL were LGA, regardless of the diabetes status of their mothers, although the highest percentages occurred in infants of nondiabetic women.
Among nondiabetic women, the relation between the screening glucose value as a continuous variable and measures of fetal growth was linear after adjusting for other demonstrated contributors to fetal growth, including gestational age and BMI. These findings demonstrate a greater independent contribution of maternal glucose tolerance to birth weight than was found in a California study that did not account for the possible effects of GDM or hypertension.10 Our data confirm that studies of the relation between the screening glucose value and fetal growth should analyze women with GDM separately and control for gestational age because of the increased probability of treatment effects, obstetric interventions that abbreviate the length of pregnancy, and unmeasured variations in comorbidity.19–22
Despite the relatively young age of our cohort (55% were younger than 25) and the conservative cutoff point of at least 140 mg/dL for GTT referral, the percentage of women with GDM was approximately double that of non-Hispanic white women, but comparable to the percentages reported for Hispanic women in several clinical studies.4,8,9 Modified criteria for the diagnosis of GDM (95, 180, 155, and 140 mg/dL at fasting and at 1, 2, and 3 hours, respectively) were adopted recently by the American Diabetes Association.12,20 If these criteria had been in use at the health center during the study period, the prevalence of GDM in our population would have been 7.5%, which is more than double that reported in a Washington study that used the modified criteria.23 The characteristics of these women with presumptive GDM were clearly distinct from the truly nondiabetic women. They closely resembled the women with diagnosed GDM in mean BMI (28.2 ± 4.4 kg/m2), screening glucose value (169.8 ± 35.4 mg/dL), likelihood of having an induced or cesarean delivery before 39.5 weeks (42.9%), and duration of gestation (38.1 ± 1.9 weeks). They were slightly older (mean age 31.8 ± 5.3 years) and more likely to have hypertensive disorders (50%) than women with GDM. None of the mothers in this group were diagnosed or treated for GDM. The adjusted mean birth weight of their infants was 3710 g. We repeated all analyses after excluding this group of women to assess their effect on the birth weight outcomes of the category of nondiabetic women whose glucose values were at least 135 mg/dL. All relations remained essentially unchanged, although the statistical power to detect these differences was limited. Further study of the effects of lower screening value cutoff points, modified diagnostic criteria, and treatment protocols on fetal growth and other maternal and infant outcomes is clearly indicated.
Despite demonstrated associations between maternal hypoglycemia and fetal growth restriction in individuals, the screening glucose value has rarely been used to understand the possible risk of SGA or low birth weight (LBW) in populations.21,24 As in other reports, SGA was rare in our cohort of Hispanic infants.25,26 The incidence of SGA only approached the expected 10% of births in the group of mothers with screening glucose levels of less than 100 mg/dL; adjusted mean birth weights were also significantly lower in this group. The linear increase in the risk of SGA observed as the screening glucose value decreased suggests the possible utility of this variable. Because glucose values and birth weight are continuous variables,11,12,21 analyzing their relation may contribute to understanding variations in birth weight distributions and the incidence of SGA and LGA among populations.
Large size for gestational age was common in the sizable proportion of our cohort who had screening values of at least 135 mg/dL. Recent studies have reported increased upper-body fatness and BP in newborn infants of GDM mothers, and greater adiposity at 1 year of age in infants of nondiabetic mothers associated with increasing maternal screening glucose level, even after adjusting for maternal BMI and pregnancy weight gain.16 This study suggests that given its demonstrated association with metabolic abnormalities, LGA may be a significant marker of maternal and infant risk in this population.5
Most research associated with birth weight among Hispanics has explored social, dietary, and behavioral aspects of traditional Hispanic culture that are presumed to explain the low risk of LBW observed in this population.9,27 Our study suggests that maternal glucose tolerance should be included in studies that examine the complex interplay of factors that influence birth weight. The increasing prevalence of obesity and type 2 diabetes among Hispanic youth in this country has gained attention recently.28,29 Design of appropriate prenatal care strategies for women with abnormal and borderline metabolic status and further research examining the effect of the intrauterine environment on the growth and subsequent health status of infants and children are needed in the Hispanic population.
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