Low enrollment

This study will conduct a randomized trial among women with gestational diabetes (GDM). Study of Pregnancy And Neonatal health (SPAN), TIMing of dElivery (TIME) is a randomized trial that will recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery. Women with GDM who are approached for the trial and are found eligible but do not consent to participating in randomization for delivery will be asked to consent for chart review only (estimated additional n=3,000). The primary objective is to determine the best time to initiate delivery for GDM-complicated deliveries (defined as the time when risk of illness and death for the newborn is the lowest) between 37-39 weeks.

This is a randomized clinical trial under an adaptive design nested in a larger observational study, among women who are diagnosed with uncontrolled gestational diabetes mellitus (GDM). Women from multiple clinical sites around the United States will be recruited into the study (n=3,450). Women with GDM who are approached for the trial and are found eligible but do not consent to participating to randomization for delivery will be asked to consent for chart review only (estimated additional n=3,000). The primary objective is to determine the optimal time to initiate delivery for GDM complicated deliveries (defined as the time when neonatal morbidity and perinatal mortality risk is the lowest) between 37-39 weeks (n=3,450 women). Newborn developmental and behavior outcomes, and anthropometric measures will also be assessed as secondary outcomes, as well as an exploratory analysis to investigate whether there are clinical, non-clinical or biochemical factors such as glucose measures that will further assist in refining the interval for optimizing time of GDM complicated deliveries relative to neonatal morbidity and perinatal mortality.

INCLUSION CRITERIA:

Aim 3 (GDM randomized trial, TIME) inclusion criteria:

Women inclusion criteria:

1. Age ≥ 18 Years

2. Verified diagnosis of Gestational Diabetes Mellitus (GDM) with abnormal glucose levels*** or meeting other criteria for poor control, specifically any one of the following: Estimated fetal weight ≥90th percentile (LGA), Polyhydramnios, and or Demonstrate noncompliance or nonadherence as defined clinically, including missing visits, not keeping accurate log, etc.

   ***One or more elevated fasting blood glucoses OR three or more elevated post-prandial blood glucoses after receiving education about appropriate diet and lifestyle modification (e.g. physical activity)

3. Accurate gestational age as verified by ultrasound

4. Singleton gestation

5. English or Spanish speaker

6. Plans to deliver at the study site hospital

7. Ability to provide informed consent to be randomized to initiation of delivery

EXCLUSION CRITERIA:

Aim 3 (GDM randomized trial, TIME) exclusion criteria:

1. Pre-gestational diabetes*

   *will be defined as diabetes diagnosis before pregnancy OR before 13 weeks of gestation with a documented fasting plasma glucose ≥ 126 mg/dL, random plasma glucose ≥ 200 mg/dL, 2 hour post glucose ≥ 200 mg/dL during an oral glucose tolerance test (75 g glucose load), or hemoglobin A1c ≥ 6.5%.110.

2. Previous stillbirth defined as fetal demise ≥ 20 weeks of gestation

3. Self-reported history of alcohol dependency disorder and/or other drug/substance dependency in the past year

4. Teratogen exposure (e.g. cyclophosphamide, valproic acid, warfarin)

5. Known infectious diseases associated with neonatal morbidity (e.g. malaria, cytomegalovirus, rubella, toxoplasmosis, syphilis or Zika virus)

6. Genetic disorders, aneuploidy and known major fetal anomalies

7. Fetal demise

8. Pregnancies with concurrent conditions and other indications for earlier delivery will also be excluded.

9. Participation in another interventional study that influences management of labor and delivery or perinatal morbidity or mortality

Anonymized phenotypic data and the SNP genotype, DNA methylation, and RNA sequence data generated from the study will be deposited into scientific databases that are maintained by the National Institutes of Health.

Data will be shared before publication or at the time of publication or shortly thereafter.

Access to the anonymised information stored in NIH archives like DASH and dbGaP will only be accepted via applications from appropriately qualified researchers who sign a legally-binding Data Access Agreement in which they commit to use the data only for research purposes; protect the data confidentiality; provide appropriate data security; not attempt to identify individual participants from whom data were obtained; and not redistribute the data or any subset or derivative that could be used to identify the research participant.