NICHD Genomic and Proteomic Network for Preterm Birth Research (GPN)

We performed genome-wide association studies (GWAS) to study the Spontaneous Preterm birth (SPTB).

Maternal and neonatal DNA from 743 SPTB (20 to and less than 34 weeks), and 752 controls (39 to and less than 42 weeks) who fully consented for public research usage were collected from participants in several clinical centers in Alabama, Illinois, New York, North Carolina, Rhode Island, Texas, and Utah. Cases were 1:1-matched with controls according to race/ethnicity (White, Hispanics, African Americans, and Others), maternal age (<20, 20-29, 30-39, 40+), and parity (yes or no). To determine the case-control status for each participant, a Gestational Age (GA) was determined.

DNA samples were taken from blood or saliva if blood was not available. Automated DNA extractions were performed on the Qiagen M48 robot, and samples were organized in 96-well plates with barcoding and sample tracking systems. Subsequent manipulations were performed on the Biomek FX liquid handling workstation with 96-channel pipetting. DNA quantitation was performed by dye-based assay on a Molecular Devices SpectraMax Plus plate reader. Samples were genotyped using Affymetrix Genome-Wide Human SNP Array 6.0. This work was conducted at the Microarray Facility at the University of Pennsylvania.

Patient data were collected through chart reviews and patient interviews, which included Demographic information (parental age, race, ethnicity, etc.); Medical history (pre-pregnancy weight, height, medications, STD history, medical conditions, etc.); Social history (marital status, years of education, alcohol use and tobacco use); Obstetrical history including outcome of all prior pregnancies and dates of termination; History of preterm labor or premature rupture of membranes symptoms, evaluation or hospitalization for those symptoms in current pregnancy; Medications taken during current pregnancy; History of cervical evaluation (manually or ultrasonographically) or fetal fibronectin measurements; Pregnancy complications; Labor (type, indications, membrane status, and induction method); Delivery type and indications for cesarean section; Neonatal outcome (sex, weight, length, Apgar score, neonatal complications, admission to intensive care unit, etc.); and Maternal family history of SPTB.

• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 2928
• Subject Sample Telemetry Report (SSTR)

• BioProject
• BioSample
• MeSH

1. Inclusion and Exclusion Criteria for Cases

1.1 Inclusion Criteria

1. Delivery between 20 weeks 0 days and 33 weeks 6 days (inclusive) following the spontaneous onset of labor.
2. pPROM that is followed at any interval by the spontaneous onset of labor at <34 weeks gestation. (Patients with pPROM that experience spontaneous labor at <34 weeks and 0 days gestation but undergo cesarean section for malpresentation or other obstetric indication are eligible for enrollment).
3. Gestational age at delivery estimated by and meeting criteria of Project gestational age.

1.2 Exclusion Criteria

1. Indicated delivery (for maternal or fetal indications).
2. Maternal uterine anomalies.
3. Multi-fetal gestations.
4. Known aneuploidy or lethal fetal anomalies.
5. Polyhydramnios (defined as Amniotic Fluid Index >/=25 cm or Deepest vertical Pocket >/=12 cm).
6. pPROM at less than 34 weeks 0 days that is not followed by spontaneous labor (if delivery occurs at any gestational age as a result of induction of labor or cesarean section without spontaneous labor the patient is excluded from enrollment).
7. Cervical Cerclage.

2. Inclusion and Exclusion Criteria for Controls

2.1 Inclusion Criteria

1. Delivery between 39 weeks 0 days and 41 weeks 6 days (inclusive).
2. PROM that is followed at any interval by the spontaneous onset of labor between 39 weeks 0 days and 41 weeks 6 days are considered eligible for enrollment. (Patients with PROM that experience spontaneous labor between 39 weeks and 0 days and 41 weeks 6 days gestation but undergo cesarean section for malpresentation or other obstetric indication are eligible for enrollment).
3. Gestational age at delivery estimated by and meeting criteria of Project gestational age.

2.2 Exclusion Criteria

1. Indicated delivery (for medical or obstetrical complications not related to preterm labor).
2. Prior history of any preterm birth (spontaneous or indicated).
3. Maternal uterine anomalies.
4. Multi-fetal gestation.
5. Known aneuploidy or lethal fetal anomalies.
6. Polyhydramnios (defined as Amniotic Fluid Index >/=25 cm or Deepest vertical Pocket >/=12 cm).
7. PROM that is not followed by the spontaneous onset of labor.
8. Cervical Cerclage.

• Primary Phenotype: Premature Birth
• Preterm Premature Rupture of Fetal Membranes

• Principal Investigators
  • Heping Zhang, PhD. Yale University, New Haven, CT, USA.
  • Joseph Biggio, MD. University of Alabama at Birmingham, Birmingham, AL, USA.
  • Radek Bukowski, MD, PhD. University of Texas Medical Branch, Galveston, TX, USA.
  • Samuel Parry, MD. University of Pennsylvania, Philadelphia, PA, USA.
  • Michael Varner, MD. University of Utah, Salt Lake City, UT, USA.
• Funding Sources
  • U01HD050062. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • U01HD050094. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • U01HD050078. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • U01HD050088. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • U01HD050080. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.