Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b)

• ClinicalTrials.gov Identifier: NCT01322529
• Recruitment Status: Completed
• First Posted: March 24, 2011
• Last Update Posted: January 12, 2016
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Office of Research on Women's Health (ORWH)
• Information provided by (Responsible Party): Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Tracking Information

• First Submitted Date: March 10, 2011
• First Posted Date: March 24, 2011
• Last Update Posted Date: January 12, 2016
• Study Start Date: September 2010
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2011)

Adverse pregnancy outcome [ Time Frame: 42 weeks project estimated gestational age or less ]

Delivery of a live born or stillborn infant due to any cause before 37 weeks 0 days project estimated gestational age, after the subject has been enrolled in the study.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01322529 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 23, 2011)

• Preterm birth [ Time Frame: 42 weeks project estimated gestational age or less ]
  Delivery of a liveborn or stillborn infant for any cause between 20 weeks 0 days and 36 weeks 6 days project estimated gestational age.
• Spontaneous preterm birth [ Time Frame: 42 weeks project estimated gestational age or less ]
  Delivery occurring subsequent to spontaneous onset of preterm labor OR preterm Premature Rupture of the Membranes (preterm PROM) OR fetal membrane prolapse, regardless of subsequent labor augmentation or cesarean delivery.
• Indicated preterm birth [ Time Frame: 42 weeks project estimated gestational age or less ]
  Delivery following induction or cesarean delivery at less than 37 weeks 0 days gestation for one or more conditions that the woman's caregiver determines to threaten the health/life of the mother or fetus. The primary diagnoses associated with indicated preterm birth are categorized as follows: pregnancy associated hypertension, fetal growth restriction, abruptio placentae, placenta previa, chorioamnionitis, abnormal fetal testing, congenital fetal anomaly(ies), maternal medical condition, other, not documented.
• Spontaneous pregnancy loss less than 20 weeks [ Time Frame: 42 weeks project estimated gestational age or less ]
  Fetal death leading to vaginal delivery or dilatation and curettage/evacuation, or spontaneous expulsion of a liveborn fetus due to any cause before 20 weeks 0 days project EGA.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be
• Official Title: Preterm Birth in Nulliparous Women: An Understudied Population at Great Risk
• Brief Summary: Forty percent of pregnant women in the United States are women who have never given birth. As a group, they sometimes have complications with their pregnancy, but there is no information from a previous pregnancy to identify who might have a problem. Very little research has been done with this group. The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) is collecting data from a diverse population of about 10,000 women who are having their first baby and are carrying only one baby. The women are enrolled early in pregnancy and undergo research assessments four times during their pregnancies. Data are collected through interviews, self-completed data forms, clinical measurements, ultrasound, and collection and storage of blood samples, urine samples, and fluid from the vagina and cervix. Some information comes from medical records. A subset of women may be asked to participate in substudies collecting information on sleep breathing, sleep patterns and quality, or other areas possibly related to birth outcomes. The goal of the research is to find ways to identify women in this group who might develop a problem with their pregnancy and use this information to improve the health of pregnant women and their babies in the future. The study is focusing on pregnancy problems like high blood pressure, babies that are born much too early and very small babies.

Detailed Description

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) to study women for whom the current pregnancy will lead to their first delivery (nulliparas). About 40% of pregnant women in the United States are nulliparas. Because little or no information from previous pregnancy outcomes is available to guide assignment of risk or mitigating interventions, adverse pregnancy outcomes in nulliparas are especially unpredictable. The underlying mechanisms of adverse pregnancy outcomes such as preterm birth, preeclampsia, fetal growth restriction and stillbirth are interrelated and therefore will be evaluated as part of this study. The information gained will benefit women who are pregnant or who are considering pregnancy and their physicians. In addition, the knowledge will support future research aimed at improving care and health outcomes for a critical group of at-risk women who are currently understudied.

The study is a prospective cohort study of a racially/ethnically/geographically diverse population of 10,038 nulliparous women with singleton gestations. The women undergo intensive research assessments during the course of their pregnancies to study the mechanisms for and prediction of adverse pregnancy outcomes (APOs) in women in their first pregnancy. The APOs of primary interest are preterm birth, preeclampsia and fetal growth restriction.

The goals of the study are to 1) determine maternal characteristics, including genetics, epigenetics, and physiological response to pregnancy as well as environmental factors that influence and/or predict adverse pregnancy outcome; 2) identify specific aspects of placental development and function that lead to adverse pregnancy outcome; and 3) characterize genetic, growth, and developmental parameters of the fetus that are associated with adverse pregnancy outcome.

Eight academic medical centers or sites had primary responsibility for enrollment and follow-up of study participants. Several of these sites collected data through additional academic research centers or nearby hospitals (subsites). A Data Coordinating and Analysis Center (DCAC) provided input to the protocol, manages the data, and analyzes the data. Investigators from these institutions have established a partnership with NICHD staff to develop and implement the study protocol and ancillary studies that acquire and analyze data to identify biomarkers and understand the mechanism and prediction of preterm birth and other adverse pregnancy outcomes.

Nulliparous women with an in utero singleton gestation between 6 weeks 0 days and 13 weeks 6 days of pregnancy were recruited through the eight clinical sites and their subsites. Mechanisms were created in the various prenatal clinics associated with the sites to identify eligible nulliparous women with singleton pregnancies. Once enrolled, a participant was followed for the duration of her pregnancy by research staff at the clinical site. Study visits were scheduled at four times during the pregnancy: 6 weeks 0 days through 13 weeks 6 days estimated gestational age (EGA), 16 weeks 0 days through 21 weeks 6 days EGA, 22 weeks 0 days through 29 weeks 6 days EGA, and at the time of delivery. Data were collected through personal interview, self-administered questionnaires, clinical measurement, chart abstraction, and collection of biological specimens (blood, urine, cervico-vaginal fluid). Additional data (i.e., sleep breathing assessments, actigraphy, fetal adrenal gland measurements) were collected through ancillary research studies on subsets of the enrolled women. The set-ups for screening, enrollment and follow-up of participants varied by clinical site and subsite. However, in each setting, the clinical site staffs included study investigators, research nurses, research assistants and sonographers. Clinical site staffs were trained to interview participants, collect and process samples, conduct various research tests, and input data. Data are managed at the DCAC. Specimens are stored at the NICHD specimen repository for later analysis.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood serum, blood plasma, maternal deoxyribonucleic acid (DNA), urine supernatant, urine cell pellet, cervico-vaginal fluid, bacterial vaginosis (BV) slide, cord blood (fetal DNA), cord blood serum, placenta, fetal membranes, umbilical cord segment, placenta and umbilical cord, chorionic villi and maternal decidua from clinical chorionic villus sampling (CVS), amniotic fluid supernatant and cell pellet from clinical amniocentesis.

• Sampling Method: Non-Probability Sample
• Study Population: The study population consists of a racially/ethnically/geographically diverse population of 10,038 nulliparous pregnant women with singleton gestations recruited through 8 participating clinical sites and their subsites.

Condition

• Pregnancy
• Pregnancy Complications

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• Haas DM, Parker CB, Wing DA, Parry S, Grobman WA, Mercer BM, Simhan HN, Hoffman MK, Silver RM, Wadhwa P, Iams JD, Koch MA, Caritis SN, Wapner RJ, Esplin MS, Elovitz MA, Foroud T, Peaceman AM, Saade GR, Willinger M, Reddy UM; NuMoM2b study. A description of the methods of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b). Am J Obstet Gynecol. 2015 Apr;212(4):539.e1-539.e24. doi: 10.1016/j.ajog.2015.01.019. Epub 2015 Jan 31.
• Facco FL, Parker CB, Reddy UM, Silver RM, Louis JM, Basner RC, Chung JH, Schubert FP, Pien GW, Redline S, Mobley DR, Koch MA, Simhan HN, Nhan-Chang CL, Parry S, Grobman WA, Haas DM, Wing DA, Mercer BM, Saade GR, Zee PC. NuMoM2b Sleep-Disordered Breathing study: objectives and methods. Am J Obstet Gynecol. 2015 Apr;212(4):542.e1-127. doi: 10.1016/j.ajog.2015.01.021. Epub 2015 Mar 4.
• Haas DM, Marsh DJ, Dang DT, Parker CB, Wing DA, Simhan HN, Grobman WA, Mercer BM, Silver RM, Hoffman MK, Parry S, Iams JD, Caritis SN, Wapner RJ, Esplin MS, Elovitz MA, Peaceman AM, Chung J, Saade GR, Reddy UM. Prescription and Other Medication Use in Pregnancy. Obstet Gynecol. 2018 May;131(5):789-798. doi: 10.1097/AOG.0000000000002579.
• Michaliszyn SF, Sjaarda LA, Scifres C, Simhan H, Arslanian SA. Maternal excess gestational weight gain and infant waist circumference: a 2-y observational study. Pediatr Res. 2017 Jan;81(1-1):63-67. doi: 10.1038/pr.2016.174. Epub 2016 Sep 15.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2016): 10038
• Original Estimated Enrollment (submitted: March 23, 2011): 10000
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Nullipara - Pregnant women with no prior pregnancy lasting 20 weeks 0 days or greater.
• Viable singleton gestation - a single living fetus with fetal cardiac activity at the most recent ultrasound before enrollment
• Between 6 weeks 0 days and 13 weeks 6 days project estimated gestational age (EGA) at first study visit.
• Intend to deliver at a participating hospital.

Exclusion Criteria:

• Participant age <13 years.
• History of 3 or more spontaneous abortions.
• Fetal malformation evident at or before enrollment that is likely lethal (e.g., anencephaly, hydrops, diffuse subcutaneous edema or cystic hygroma, ectopic cordis, encephalocele).
• Known fetal aneuploidy (based on chorionic villus sampling).
• Surrogate pregnancy (donor oocyte pregnancy).
• Multifetal reduction.
• Participating in an intervention study that is anticipated to influence maternal or fetal morbidities/mortality unless it is determined before enrollment that the study code will be made available.
• Woman previously enrolled in this study, including those consented but delivered before 20 weeks 0 days gestation.
• Planned pregnancy termination.
• Unable to provide informed consent.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 13 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01322529
• Other Study ID Numbers: NICHD-nuMoM2b-001; 1U10HD063036-01 ( U.S. NIH Grant/Contract ); 1U10HD063072-01 ( U.S. NIH Grant/Contract ); 1U10HD063047-01 ( U.S. NIH Grant/Contract ); 1U10HD063037-01 ( U.S. NIH Grant/Contract ); 1U10HD063041-01 ( U.S. NIH Grant/Contract ); 1U10HD063020-01 ( U.S. NIH Grant/Contract ); 1U10HD063046-01 ( U.S. NIH Grant/Contract ); 1U10HD063048-01 ( U.S. NIH Grant/Contract ); 1U10HD063053-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: Date will be made available to authorized researchers in the future through a yet to be determined government repository.

• Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Study Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• Office of Research on Women's Health (ORWH)

Investigators

• Study Chair: George Saade, M.D.; University of Texas
• Principal Investigator: Brian M Mercer, M.D.; Case Western Reserve University
• Principal Investigator: Ronald Wapner, M.D.; Columbia University
• Principal Investigator: David M Haas, M.D., M.S.; Indiana University
• Principal Investigator: Hyagriv N Simhan, MD, MSCR; Magee-Women's Hospital - University of Pittsburgh
• Principal Investigator: William Grobman, M.D., M.B.A.; Northwestern University
• Principal Investigator: Deborah A Wing, M.D.; University of California, Irvine
• Principal Investigator: Samuel Parry, M.D.; University of Pennsylvania
• Principal Investigator: Robert M Silver, M.D.; University of Utah
• Principal Investigator: Cora (Corette) B Parker, MSPH, DrPH; RTI International

• PRS Account: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Verification Date: January 2016