Mengying Li1, Stefanie N Hinkle1, Katherine L Grantz1, Sungduk Kim2, Jagteshwar Grewal1, William A Grobman3, Daniel W Skupski4, Roger B Newman5, Edward K Chien6, Anthony Sciscione7, Noelia Zork8, Deborah A Wing9, Michael Nageotte10, Fasil Tekola-Ayele1, Germaine M Buck Louis11, Paul S Albert2, Cuilin Zhang12. 1. Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 3. Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. 4. Department of Obstetrics and Gynecology, New York-Presbyterian Hospital Queens, Flushing, NY, USA. 5. Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA. 6. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, Providence, RI, USA. 7. Christiana Care Health System, Newark, DE, USA. 8. Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA. 9. Division of Maternal-Fetal Medicine, Department of Obstetrics-Gynecology, University of California School of Medicine, Irvine, CA, USA; Fountain Valley Regional Hospital and Medical Center, Fountain Valley, CA, USA. 10. Long Beach Memorial Medical Center, Long Beach, CA, USA. 11. College of Health and Human Services, George Mason University, VA, USA. 12. Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: zhangcu@mail.nih.gov.
Abstract
BACKGROUND: The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. METHODS: This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18-40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8-13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10-14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov, NCT00912132. FINDINGS: Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28-40 (at week 37: 3061 g [95% CI 2967-3164] for women with gestational diabetes vs 2943 g [2924-2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10-14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983-3167] in the highest tertile vs 2853 g [2755-2955] in the lowest tertile, adjusted p=0·0009. INTERPRETATION:Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24-28 gestational weeks, when gestational diabetes is typically screened for in the USA. FUNDING: National Institutes of Health.
RCT Entities:
BACKGROUND: The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. METHODS: This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18-40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8-13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10-14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov, NCT00912132. FINDINGS: Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28-40 (at week 37: 3061 g [95% CI 2967-3164] for women with gestational diabetes vs 2943 g [2924-2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10-14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983-3167] in the highest tertile vs 2853 g [2755-2955] in the lowest tertile, adjusted p=0·0009. INTERPRETATION:Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24-28 gestational weeks, when gestational diabetes is typically screened for in the USA. FUNDING: National Institutes of Health.
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