Obstetrics & Gynecology:
Perinatal Outcomes in Hispanic and Non-Hispanic White Women With Mild Gestational Diabetes
Berggren, Erica K. MD; Mele, Lisa ScM; Landon, Mark B. MD; Spong, Catherine Y. MD; Ramin, Susan M. MD; Casey, Brian MD; Wapner, Ronald J. MD; Varner, Michael W. MD; Rouse, Dwight J. MD; Sciscione, Anthony DO; Catalano, Patrick MD; Harper, Margaret MD, MSc; Saade, George MD; Caritis, Steve N. MD; Sorokin, Yoram MD; Peaceman, Alan M. MD; Tolosa, Jorge E. MD, MSCE; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Departments of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, The Ohio State University, Columbus, Ohio, University of Texas Health Science Center at Houston, Houston, Texas, University of Texas Southwestern Medical Center, Dallas, Texas, Columbia University, New York, New York, University of Utah, Salt Lake City, Utah, University of Alabama at Birmingham, Birmingham, Alabama, Drexel University, Philadelphia, Pennsylvania, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio, Wake Forest University Health Sciences, Winston-Salem, North Carolina, University of Texas Medical Branch, Galveston, Texas, University of Pittsburgh, Pittsburgh, Pennsylvania, Wayne State University, Detroit, Michigan, Northwestern University, Chicago, Illinois, and Oregon Health & Science University, Portland, Oregon; the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Corresponding author: Erica K. Berggren, MD, Jefferson Medical College of Thomas Jefferson University, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, 834 Chestnut Street, Suite 400, Philadelphia, PA 19107; e-mail: firstname.lastname@example.org.
* For a list of other members of the NICHD MFMU, see the Appendix online at http://links.lww.com/AOG/A322.
The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801), General Clinical Research Centers Grant (M01-RR00034), and the National Center for Research Resources (UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234) and does not necessarily represent the official views of the NICHD or the National Institutes of Health (NIH).
The authors thank Francee Johnson, RN, BSN, and Jo-Ann Tillinghast, RN, MSN, for protocol development and coordination between clinical research centers; Elizabeth Thom, PhD, for protocol and data management and statistical analysis; and John M. Thorp, Jr, MD, for protocol development and oversight.
Dr. Spong, Associate Editor of Obstetrics & Gynecology, was not involved in the review or decision to publish this article.
Financial Disclosure The authors did not disclose any potential conflicts of interest.
OBJECTIVE: To compare perinatal outcomes between self-identified Hispanic and non-Hispanic white women with mild gestational diabetes mellitus (GDM) or glucose intolerance.
METHODS: In a secondary analysis of a mild GDM treatment trial, we compared perinatal outcomes by race and ethnicity for 767 women with glucose intolerance (abnormal 50-g 1-hour screen, normal 100-g 3-hour oral glucose tolerance test), 371 women with mild GDM assigned to usual prenatal care, and 397 women with mild GDM assigned to treatment. Outcomes included: composite adverse perinatal outcome (neonatal death, hypoglycemia, hyperbilirubinemia, hyperinsulinemia, stillbirth, birth trauma), gestational age at delivery, birth weight, and hypertensive disorders of pregnancy. Adjusted regression models included: 100-g 3-hour oral glucose tolerance test results, parity, gestational age, body mass index, maternal age at enrollment, and current tobacco use.
RESULTS: The sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Among women with glucose intolerance, Hispanic women had more frequent composite outcome (37% compared with 27%, adjusted odds ratio [OR] 1.62, 95% confidence interval [CI] 1.10–2.37) with more neonatal elevated C-cord peptide (19% compared with 13%, adjusted OR 1.79, 95% CI 1.04–3.08) and neonatal hypoglycemia (21% compared with 13%, adjusted OR 2.04, 95% CI 1.18–3.53). Among women with untreated mild GDM, outcomes were similar by race and ethnicity. Among Hispanic women with treated mild GDM, composite outcome was similar to non-Hispanic white women (35% compared with 25%, adjusted OR 1.62, 95% CI 0.92–2.86), but Hispanic neonates had more frequent hyperinsulinemia (21% compared with 10%, adjusted OR 2.96, 95% CI 1.33–6.60).
CONCLUSION: Individual components of some neonatal outcomes were more frequent in Hispanic neonates, but most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups.
LEVEL OF EVIDENCE: II
Gestational diabetes mellitus (GDM) complicates 4–7% of all pregnancies, and its prevalence continues to rise in parallel with the evolving obesity epidemic.1 Hispanic women in the United States have a higher prevalence of GDM compared with white or African American women.2–5 Across racial and ethnic groups, hyperglycemia increases risks of adverse perinatal outcomes, including large for gestational age, shoulder dystocia, cesarean delivery, and hypertensive disorders of pregnancy.6,7 Strict glycemic control decreases risks of these outcomes.8
Whether the risk of adverse outcomes associated with mild GDM differs by race and ethnicity, however, is less clear. Among those without GDM, Hispanic women experience lower neonatal mortality, are less likely to deliver low-birth-weight neonates,9,10 and have had a lower reported prevalence of preeclampsia compared with white and African American women.11 Although some data suggest adverse outcome risk may also vary by race and ethnicity among women with GDM,5,12–14 findings are not consistent. Thus, whether differences are specific to GDM or related to race and ethnicity independent of hyperglycemia is uncertain.
To address this uncertainty, we analyzed a large cohort of women with glucose intolerance, and untreated and treated mild GDM, but not overt diabetes of pregnancy, and measured differences in perinatal outcomes by race or ethnicity.
MATERIALS AND METHODS
We performed a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network multisite randomized clinical trial for the treatment of mild GDM15 and compared perinatal outcomes by self-reported race and ethnicity. We compared women self-reported as Hispanic (including Mexican American, Central and South American, or Caribbean) with women self-reported as white (and not Mexican American, Central and South American, or Caribbean). A total of eight women self-reported their race and ethnicity as Hispanic as well as African American or Native American or Alaskan; these eight women were included in the Hispanic group.
Women were eligible if they had a 1-hour 50-g glucose load test result between 135 and 200 mg/dL between 24 0/7 weeks and 30 6/7 weeks of gestation. They were excluded if they had pregestational diabetes; an abnormal glucose screening test before 24 weeks of gestation; a history of GDM; stillbirth, multifetal gestation, asthma, or chronic hypertension; if taking corticosteroids; or if imminent preterm delivery was anticipated. The original study sample and randomization process has been further described previously.15 In the original study, eligible women with an elevated 50-g 1-hour glucose load result underwent a 100-g 3-hour oral glucose tolerance test (OGTT) and these results diagnosed mild GDM. Women were randomized to treatment compared with no treatment, matched for race and ethnicity and body mass index (BMI [calculated as weight (kg)/height (m2)]) less than compared with equal to or more than 27). Women with normal OGTT results were enrolled as the observational cohort. The primary composite adverse perinatal outcome for the original study was occurrence of one or more of the following: perinatal mortality (stillbirth or perinatal death), hypoglycemia, hyperbilirubinemia, elevated cord blood C-peptide level, or birth trauma.15 The sample size for the current study was constrained by the sample size of the original trial. The original study was approved by the institutional review board at each participating center, and all participating women provided written informed consent.
A total of 1,889 women were enrolled in the original study, including 1,535 who were either Hispanic or non-Hispanic white. These 1,535 women were classified into one of three groups in the parent study: 1) 767 women with glucose intolerance with an elevated 50-g 1-hour screening test (135 or greater but less than 200 mg/dL) but normal 3-hour OGTT matched to the randomized patients by clinical center, race or ethnicity, and BMI; 2) 371 women with mild GDM as diagnosed by a fasting glucose less than 95 mg/dL but two or more 100-g 3-hour OGTT results at or above established thresholds16 who were randomized to no treatment; and 3) 397 women also diagnosed with mild GDM by the same criteria as above but who were randomized to treatment. Women were randomly assigned to no treatment compared with treatment (nutritional counseling and diet therapy with insulin if required) by the simple urn method17 as previously described.15
We report overall and individual components of the composite outcome: hyperbilirubinemia, elevated cord blood C-peptide, and hypoglycemia. Perinatal mortality and birth trauma are not included in individual analyses as a result of small numbers for each.15 We also evaluated gestational age at delivery (weeks of gestation, preterm birth less than 37 weeks of gestation), birth weight (grams, small for gestational age, large for gestational age, macrosomia greater than 4,000 g), either gestational hypertension or preeclampsia, and neonatal intensive care unit admission. Identification of large for gestational age used growth standards that accounted for race and Hispanic ethnicity, like in the original study.18 Study personnel abstracted pertinent data for enrolled women and their newborns at the time of hospital discharge.
We compared baseline demographic characteristics and perinatal outcomes by Hispanic compared with non-Hispanic white race and ethnicity. We used Student’s t test for continuous variables and χ2 or Fisher’s exact test for categorical variables. For each perinatal outcome, we performed multiple linear or logistic regression analysis for continuous and categorical outcomes, respectively. All adjusted models included: fasting, 1, 2, and 3-hour results of 100-g 3-hour OGTT; parity; gestational age at enrollment; prepregnancy BMI; maternal age at enrollment; and tobacco use in current pregnancy.
Statistical analyses were conducted with SAS software. A nominal two-sided P<.05 was considered to indicate statistical significance and no adjustments were made for multiple comparisons.
Our sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Race and ethnicity were similar (P=.90) among the three cohorts. Hispanic and non-Hispanic white women in the treated mild GDM cohort were equally likely to receive insulin (1.2% compared with 2.3%, P=.09).
Demographic characteristics by race and ethnicity are shown in Table 1. Results of GDM screening (50-g 1-hour glucose load) and diagnostic (100-g 3-hour oral OGTT) tests are shown in Table 2. For all three cohorts, 50-g 1-hour oral glucose load results were similar by race or ethnicity. In the glucose-intolerant cohort, Hispanic women had higher 100-g 3-hour OGTT results at 1 hour (156.3 compared with 151.2 mg/dL, P=.006) and 3 hours (111.6 compared with 105.3 mg/dL, P<.001). In the untreated mild GDM cohort, Hispanic women had higher 100-g 3-hour OGTT results at 3 hours (136.7 compared with 128.6 mg/dL, P=.02). In the treated mild GDM cohort, Hispanic women had greater 100-g 3-hour OGTT results at the time of fasting (86.9 compared with 85.5 mg/dL, P=.04) and 100-g 3-hour OGTT results at 3 hours (140.3 compared with 133.3 mg/dL, P=.02).
Results for women in the glucose-intolerant cohort are shown in Table 3. Hispanic women had more frequent composite perinatal outcome. The observed increased risk of composite perinatal outcomes among Hispanic neonates is driven by their increased risk of hyperinsulinemia and hypoglycemia. Gestational age at delivery was greater among Hispanic women, but mean gestational age was greater than 39 weeks for both groups. Other secondary perinatal outcomes were similar.
Results for women with untreated mild GDM are shown in Table 3. Non-Hispanic white and Hispanic women had similar prevalence of the composite perinatal outcome and each of the three reported outcome components is similar between groups. Like in the glucose-intolerant cohort, Hispanic women with untreated mild GDM delivered at a greater gestational age, but this difference was less than 4 days. Other secondary outcomes were similar between groups.
Results for women in the treated mild GDM cohort are shown in Table 3. Composite neonatal outcome prevalence did not differ between groups. The 10% greater prevalence of the composite outcome, equal to the prevalence difference in the glucose-intolerant cohort, is driven by the increased risk of elevated cord C-peptide among Hispanic women. Like in the other two cohorts, Hispanic women with untreated mild GDM delivered at a greater gestational age, but this difference was less than 4 days. Other secondary outcomes were equally likely between groups.
Mexican American women comprised 75% of all women classified as Hispanic. Significant differences in the composite outcome reported among all Hispanic women, compared with non-Hispanic white women, remained significant when only Mexican American women were compared with non-Hispanic white women. Outcomes among the smaller subsets of Central or South American women and Caribbean women, also classified as Hispanic, compared with non-Hispanic white women, were not different.
Among women with glucose intolerance and with treated or untreated mild GDM, Hispanic neonates were more likely to experience adverse neonatal outcomes, although not in a uniform pattern, and maternal outcomes did not differ by race or ethnicity. Our data do not support racial and ethnic tailored diagnostic thresholds as suggested in reports of women with overt GDM.
Our findings differ from other published data that illustrate the Hispanic Paradox, a term used to describe the better-than-expected outcomes among a socioeconomically disadvantaged racial or ethnic group, more likely to live in poverty than their non-Hispanic white counterparts, and more similar to African American than non-Hispanic populations.19 Although GDM prevalence is higher among Hispanic women, other important outcomes such as low birth weight remain lower.20–22 Others3,11,14,23 have reported on the differences in hyperglycemia-associated adverse outcomes among neonates of Hispanic women with GDM when compared with other races and ethnicities.
Results have been inconsistent. One report found that when compared with white women, Hispanic women were more likely to achieve glycemic control with diet alone in one large cohort.14 Data from another large cohort reported that Hispanic women were more likely to require medical management of their GDM.23 Hispanic women in the latter cohort had less frequent hypertensive disorders of pregnancy and fewer preterm births, but more frequent shoulder dystocia, when compared with white women.
Retrospective analyses without a non-GDM group or groups with varying degrees of hyperglycemia have limitations. Inconsistent differences in adverse outcomes by race and ethnicity may be specific to GDM pathophysiology or mechanisms of insulin resistance as has been proposed. A recent analysis of statewide birth certificate data suggested the effect size of racial and ethnic differences in outcomes among GDM is not large enough to support racial- and ethnic-specific GDM diagnosis and treatment thresholds.24 Our results support this conclusion, and our analysis was able to overcome some limitations of these prior studies.
A primary strength of our study was our ability to evaluate racial and ethnic differences among women with mild hyperglycemia. These women are at increased risk of adverse outcomes but not diagnosed or treated by current diagnostic thresholds. The randomization of women with mild GDM in the original trial allowed us to evaluate racial and ethnic differences in women who are treated and not treated. A cohort of women with glucose intolerance but no GDM allowed us to compare racial and ethnic differences even among women with hyperglycemia below the most inclusive thresholds warranting treatment. Because only women in the treated mild GDM cohort were eligible for insulin and the overall proportion of women receiving insulin was low and similar by race and ethnicity, treatment type did not likely bias our results. Finally, a large sample size and rigorously collected prospective data allowed us to examine several relative perinatal outcomes and consider multiple potential confounders in adjusted analyses.
This secondary analysis also has limitations. Although our study population was over two-thirds Hispanic, it remains a heterogenous group, and data on women’s culture of origin are limited. Length of time in the United States and acculturation, measured by English proficiency, may minimize the paradoxical improved health seen in Hispanic women.9,22 Our data did not include measures of acculturation, so we were unable to evaluate this potential confounder. Although our reported statistical differences only persist when Mexican women are compared with non-Hispanic white women, this is likely the result of small numbers of women from other countries. Without adequate numbers to power such a subanalysis, these data are exploratory only. Larger numbers of South or Central American or Caribbean women would be required to evaluate these differences.
In addition, the primary trial was not powered to the outcomes used in this secondary analysis and lack of statistical significance may represent a β error. For example, the difference in primary composite outcome is significant by race and ethnicity in the glucose-intolerant groups. However, although the prevalence of this outcome is mirrored among Hispanic and non-Hispanic white women in the treated mild GDM cohort, this is not statistically significant. Despite these limitations, this secondary analysis of a large, prospective, randomized controlled trial of mild GDM demonstrates that most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups. Only individual components of neonatal outcomes were more frequent in Hispanic neonates.
Growing support to implement more inclusive GDM diagnostic criteria will further increase GDM prevalence. A substantial proportion of women will still have some degree of hyperglycemia but not be diagnosed and treated for GDM. The overall high prevalence of adverse outcomes among these women without overt GDM, however, highlights an area for research. Additional efforts may target at-risk women with hyperglycemia, but not overt GDM, for intervention and treatment regardless of race and ethnicity. Our findings suggest that diagnostic criteria tailored to race and ethnicity may not be warranted, at least not among women with mild GDM or glucose intolerance. If tailored treatment to optimize glycemic control among Hispanic women is pursued, we would suggest using specific neonatal diagnoses—such as C-cord peptide or neonatal hypoglycemia—as study outcomes.
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