Study of Pregnancy and Neonatal Health (SPAN), Pregnancy Cohort Investigating Paternal Contributions, Placental/Fetal Genetics, and Timing of Delivery on Neonatal Health

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05515744

Collaborator

(none)

29,875

Enrollment

Location

Arms

Anticipated Duration (Months)

466.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Poor health in a newborn can have lifelong effects. Researchers want to understand more about the factors that influence fetal and neonatal health.

Objective:

To investigate 3 factors that may affect the health of a newborn:

The father s cardiovascular health
Genetic factors that affect the fetus and placenta
Timing of delivery for women with gestational diabetes (GDM)

Eligibility:

Women aged 18 years or older who are less than 20 weeks pregnant with 1 child. Biological fathers aged 18 years or older are also needed. The study also seeks pregnant women with GDM and/or who identify as Black or African American.

Design:

Women will participate until delivery. They will complete an online questionnaire. Topics include their medical history, lifestyle, and partner s health. Women s first clinic visit will take 1 hour. They will have a physical exam and provide blood, urine, and saliva. Their body dimensions and circulatory health will be measured. Women will have an ultrasound exam during their third trimester. Fetal growth and measures of placental function will be measured. Some women with GDM will be randomly assigned to deliver their babies in a 3-day window sometime between 37 and 39 weeks of gestation. Women will provide a blood sample at delivery. Their placentas will be measured and tissue samples collected. Newborns will be measured and weighed. Their behavioral and neurological development will be tested. Men will complete an online questionnaire. In 1 clinic visit, they will have a physical exam. Their bodies and circulatory health will be measured. They will provide blood and urine. Some will provide semen samples once or twice and a scan for body fat and bone health.

Condition or Disease	Intervention/Treatment	Phase
Diabetes, Gestational Pregnancy Anthropometry, Neonatal	Procedure: Initiation of delivery	Phase 3

Detailed Description

Study Description:

This study will establish a cohort from multiple sites to collect common data elements and conduct a randomized trial among women with gestational diabetes (GDM).

Objectives:

Aim 1: To determine whether paternal cardiovascular (CVD) risk factors (i.e., BMI, waist circumference, percent body fat, HbA1c, blood pressure, arterial stiffness) are associated with fetal growth, neonatal anthropometry, and placental function (as measured by ultrasound and placental characteristics at delivery); and whether semen epigenetic differences explain associations.

Aim 2: To identify fetal genetic loci that influence fetal growth and birth anthropometry, and to determine fetal genetic loci associated with placental age acceleration and the functional link between associated genetic loci, placental gene expression and fetal growth. The discovery study will be done in African Americans followed by validation and trans-ethnic meta-analyses involving other race/ethnic groups.

Aim 3: To determine the optimal time to initiate delivery for GDM complicated deliveries between 37-39 weeks where neonatal morbidity and perinatal mortality is the lowest (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.

Endpoints:

Outcome measures for all Aims include fetal growth as measured by ultrasound (i.e, fetal weight, head circumference, abdominal circumference, humerus and femur lengths), maternal morbidity and mortality, pregnancy outcomes, placental characteristics as measured by ultrasound during gestation and by physical examination at delivery (e.g., placental weight and thickness, placental volume, vascularization index), placental DNA methylation profile and epigenetic age acceleration (a measure calculated as the difference between placental epigenetic age and gestational age at delivery), and neonatal outcomes (i.e., mortality and morbidity, neonatal body fat, anthropometry, size for gestational age, neurobehavioral assessment using the NICU Network Neurobehavioral Scale).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

29875 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of Pregnancy and Neonatal Health (SPAN), Pregnancy Cohort Investigating Paternal Contributions, Placental/Fetal Genetics, and Timing of Delivery on Neonatal Health

Anticipated Study Start Date :

Aug 30, 2022

Anticipated Primary Completion Date :

Dec 31, 2027

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 37 weeks 0 days 37 weeks 2 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.
Experimental: 2 37 weeks 3 days 37 weeks 5 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.
Experimental: 3 37 weeks 6 days 38 weeks 1 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.
Experimental: 4 38 weeks 2 days 38 weeks 4 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.
Experimental: 5 38 weeks 5 days 39 weeks 0 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.
Experimental: 6 39 weeks 1 days 39 weeks 3 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.
Experimental: 7 39 weeks 4 days 39 weeks 6 days	Procedure: Initiation of delivery By default, labor will be induced. Cesarean section will be reserved per usual obstetrical indications.

Outcome Measures

Primary Outcome Measures

neonatal morbidity and perinatal mortality [Hospital discharge]
Individual and composite indicators of neonatal morbidity and perinatal mortality

Secondary Outcome Measures

Neonatal outcomes [Hospital discharge]
Individual and composite indicators of neonatal well-being
Neonatal anthropometry [24-48 hours after birth]
PeaPod and body measurements
Maternal obstetric outcomes [Hospital discharge]
Individual and composite indicators maternal morbidity
Maternal mortality and morbidity [Hospital discharge]
Individual and composite indicators of severe maternal outcomes
Neonatal development and behavior [24-48 hours after birth]
NICU Network Neurobehavioral Scale (NNNS-II)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

The eligibility of the 3 aims of SPAN are provided below. Eligible women can participate in all 3 aims. For the cohort study, women should be recruited as early as possible in pregnancy but no later than 19w6d of pregnancy. Women with a diagnosis of GDM can be enrolled at up to 36weeks of gestation for the randomized trial (aim 3). Enrollment forms will be used to verify eligibility for the cohort and specifically for timing of delivery. Refusal information will only be reported anonymously to better improve recruitment efforts. Information from consented participants will be entered into NICHD CTDB.

Aim 1 (paternal factors) inclusion criteria:

Women INCLUSION CRITERIA:

Age >=18 Years
< 20 weeks, 0 days gestation (as verified by ultrasound)
English or Spanish speaker
Singleton gestation
Does not expect to terminate the pregnancy
Plans to deliver at the study site hospital
Ability to provide informed consent
Male partner willing to provide informed consent

Male partners INCLUSION CRITERIA:

Age >=18 Years
Biological father of the baby (i.e., no donor sperm but fertility treatment allowed)
English or Spanish speaker
Ability to attend study site for study exam
Ability to provide informed consent
Female/Pregnant partner willing to provide informed consent

Aim 2 (fetal genetics, gGAP) aim INCLUSION CRITERIA:

Self-reported Black or African American
Age >=18 Years
< 20 weeks, 0 days gestation (as verified by ultrasound)
English or Spanish speaker
Singleton gestation
Does not expect to terminate the pregnancy
Plans to deliver at the study site hospital
Ability to provide informed consent

(Note: Male partners of African American pregnant women can be recruited into aim 1.)

Aim 3 (GDM randomized trial, TIME) INCLUSION CRITERIA:

Women INCLUSION CRITERIA:

Age >=18 Years
Verified diagnosis of GDM with abnormal glucose levels or meeting other criteria for poor control, specifically any one of the following:
One or more elevated fasting blood glucoses OR three or more elevated postprandial blood glucoses after receiving education about appropriate diet and lifestyle modification (e.g. physical activity)
Estimated fetal weight >=90th percentile (LGA)
Polyhydramnios
Demonstrate noncompliance or nonadherence as defined clinically, including missing visits, not keeping accurate log, etc.
Accurate gestational age as verified by ultrasound
Singleton gestation
English or Spanish speaker
Plans to deliver at the study site hospital
Ability to provide informed consent to be randomized to initiation of delivery at gestational age 35 weeks 0 days to 36 weeks 6 days

EXCLUSION CRITERIA:

Aim 3 (GDM randomized trial, TIME) EXCLUSION CRITERIA:

Pre-gestational diabetes
Previous stillbirth defined as fetal demise >= 20 weeks of gestation
Self-reported history of alcohol dependency disorder and/or other drug/substance dependency in the past year
Teratogen exposure (e.g. cyclophosphamide, valproic acid, warfarin)
Known infectious diseases associated with neonatal morbidity (e.g. malaria, cytomegalovirus, rubella, toxoplasmosis, syphilis or Zika virus)
Genetic disorders, aneuploidy and known major fetal anomalies
Fetal demise
Pregnancies with concurrent conditions and other indications for earlier delivery will also be excluded.99 Common examples include:
Signs of labor (regular painful contractions with cervical change)
Ruptured membranes
Placenta or vasa previa
Prior classical cesarean
Prior myomectomy
Previous uterine rupture
Oligohydramnios defined as amniotic fluid index < 5 cm or single deepest pocket < 2 cm
Fetal growth restriction (defined as estimated fetal weight < 10th percentile)
Abnormal umbilical artery Doppler velocimetry results defined as pulsatility index > 95th percentile for gestational age
Alloimmunization
Chronic hypertension that is difficult to control (requiring frequent medication adjustments)
Gestational hypertension at randomization
Preeclampsia at randomization
HIV because of modified delivery plan
Intrahepatic cholestasis of pregnancy
Chronic renal insufficiency, renal failure
Antiphospholipid antibody syndrome
Systemic lupus erythematosus
Hemoglobinopathies such as sickle cell disease
History of organ transplantation
Participation in another interventional study that influences management of labor and delivery or perinatal morbidity or mortality

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institute of Child Health and Human Development	Bethesda	Maryland	United States	20817

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator: Edwina HY Yeung, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

ClinicalTrials.gov Identifier:

NCT05515744

Other Study ID Numbers:

10000737
000737-CH

First Posted:

Aug 25, 2022

Last Update Posted:

Aug 25, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Fathers

Diabetes, Gestational

Anthropometry, Neonatal

Additional relevant MeSH terms:

Diabetes, Gestational

Study Results

No Results Posted as of Aug 25, 2022