Clinical trial NCT02231398: nuMoM2b Heart Health Study
Official title: Pregnancy as a Window to Future Cardiovascular Health: Adverse Pregnancy Outcomes as Predictors of Increased Risk Factors for Cardiovascular Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy Complicated by Cardiovascular Disorders as Postpartum Condition, Delivered During Previous Episode
Breathing-Related Sleep Disorder
Keywords: Cardiovascular disease
Pregnant women
Nulliparity
Pregnancy outcomes
Pregnancy complications
Sleep disordered breathing
Lead sponsor: RTI International
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2014-09-04
Enrollment: 4509
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible women are recruited from the cohort enrolled to nuMoM2b. For nuMom2b a convenience sample was recruited through 8 primary clinical sites that NIH selected because they could each demonstrate access to more than 4,500 deliveries per year. As a group, sites were geographically dispersed and ethically diverse. All nulliparous women aged 13 years or greater with a singleton pregnancy less than 13 weeks 6 days gestation who presented at recruitment clinics or practices and planned to deliver at a study hospital were potentially eligible for participation. A clinical or research ultrasound, performed by a study certified sonographer, confirmed viability of a singleton gestation with no obvious malformations and estimated gestational age less than or equal to 13 weeks 6 days before the woman was allowed enrollment. The first visit was scheduled and completed within a window of 6 weeks 0 days and 13 weeks 6 days estimated gestational age.

Brief summary: This study is looking at the relationship between experiences during pregnancy and cardiovascular health 2 to 3½ years later. The investigators are recruiting women from the approximately 10,000 women who were enrolled and followed over the course of their first pregnancy in another study.

Detailed description: The National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is funding this follow-up study of the nuMoM2b cohort to evaluate the association between adverse pregnancy outcomes (APOs) and cardiovascular health approximately 2 to 3½ years postpartum. The study, called the nuMoM2b Heart Health Study or nuMoM2b HHS, utilizes the extensive database and tissue bank developed for nuMoM2b in which nulliparous women are evaluated over the course of pregnancy to study the mechanisms for and prediction of APOs. Women enrolled in the nuMoM2b cohort are extremely well phenotyped through prospective data collection, clinical evaluations, and ultrasound assessments, as well as through the use of standardized definitions. Demographic, psychosocial, dietary, physiologic, and outcome information were collected through maternal interviews, self-administered questionnaires, clinical measurements, ultrasounds, and medical record abstraction. Samples of maternal blood, urine, and cervico-vaginal fluid over pregnancy and cord blood and placenta at delivery were collected and banked. All women completed two sleep questionnaires and over 3,600 had objective overnight sleep studies at two times during pregnancy.

Women participating in the nuMoM2b are assessed in nuMoM2b HHS for evidence of cardiovascular disease risk (CVDR), including sleep disordered breathing (SDB), at 2 to 3½ years postpartum. APOs in subsequent pregnancies also are assessed. This study characterizes the relationship between APOs and CVDR, identify first pregnancy profiles that portend subsequent CVDR, determine associations between SDB during the first pregnancy and subsequent CVDR, and identify modifiable factors that mediate the associations between CVDR and APOs in the first and subsequent pregnancy. This follow-up study will allow for the development of strategies to modify these CVDR factors and to improve the health of women suffering APOs.

The nuMoM2b Heart Health Study is a prospective observational study that includes interval contacts and a detailed cardiovascular assessment 2 to 3½ years after delivery of the index pregnancy. At the cardiovascular assessment, potentially eligible women are invited to attend a cardiovascular screening visit. After informed consent, a urine pregnancy test is performed to confirm eligibility. The visit includes clinical and laboratory measurements as well as a structured interview to assess domains that were measured in the nuMoM2b pregnancy: physical activity, depression, social support, psychological stress, and nutritional status. Women with sleep breathing assessments during their nuMoM2b pregnancy are offered another overnight sleep study.

The overarching goal is to better define the relation between outcomes of pregnancy and long term health of the mother. The specific aims are as follows:

Aim 1: Define the incidence of hypertension and the cardiovascular disease risk (CVDR) profile of women approximately 2 to 3½ years after a first pregnancy complicated by preeclampsia or other adverse pregnancy outcomes (APOs: stillbirth, small for gestational age at birth \[SGA\], preterm birth, preeclampsia, pregnancy-associated hypertension, gestational diabetes \[GDM\]) compared to women having no APOs in the first pregnancy.

Aim 2: Identify a profile in early pregnancy that portends subsequent CVDR approximately 2 to 3½ years postpartum.

Aim 3: Determine whether pregnancy and postpartum sleep disordered breathing (SDB) is associated with increased CVDR and identify specific patterns of pregnancy and postpartum SDB that increase CVDR.

Aim 4: Identify modifiable factors during and after pregnancy that mediate the associations between APOs and the CVDR during pregnancy and approximately 2 to 3½ years postpartum.

Eligibility criteria: Inclusion Criteria:

Interval Contact:

* Agreed to contact for future studies during nuMoM2b and not subsequently withdrawn from the cohort.
* Have pregnancy outcome data from the nuMoM2b study.
* At least 18 years of age (to begin interval contact attempts once nuMoM2b participant reaches age 18).
* Provision of verbal consent for telephone interview or acknowledgement of consent with completion of the web-based self-administered questionnaire.

In-clinic Visit:

* Consented for participation in interval contacts and not subsequently withdrawn
* Between 2 and 3.5 years after the nuMoM2b pregnancy ended
* Self-report at least 6 months postpartum from any subsequent pregnancy
* Self-report not currently pregnant
* Able to provide informed consent
* Provision of written, signed, informed consent for the 2 to 3.5 year in-clinic assessment
* Not currently pregnant by urine pregnancy test administered in the clinic following consent

In-home Sleep Breathing Assessment after the In-Clinic Visit:

* Participation in the in-clinic visit
* Participation in the sleep breathing substudy of nuMoM2b with at least one sleep breathing assessment providing valid data
* Not currently using positive airway pressure (PAP) therapy or other approved treatments for sleep apnea such as oral appliances and nasal therapy patch (Provent)
* Not currently on continuous oral steroid therapy for 14 days or more to treat asthma
* Not currently using oxygen supplementation to treat a medical condition
* Able to provide informed consent and deemed likely to return equipment in a reasonable period
* Provision of written, signed, informed consent for the sleep breathing assessment for the nuMoM2b Heart Health Study

Exclusion Criteria:

* Inability or refusal to provide informed consent for the study component.

Primary outcomes:
measure: Hypertension, defined as systolic blood pressure above 140 mm Hg or diastolic blood pressure above 90 mm Hg
timeFrame: Blood pressures taken at study clinic visit between 2 and 3.5 years postpartum
Secondary outcomes:
measure: Systolic blood pressure in mm Hg
timeFrame: Blood pressures taken at study clinic visit between 2 and 3.5 years postpartum
measure: Diastolic blood pressures in mm Hg
timeFrame: Blood pressures taken at study clinic visit between 2 and 3.5 years postpartum
measure: HDL cholesterol in mg/dL from blood sample following overnight fast of at least 8 hours
timeFrame: Blood sample taken at study clinic visit between 2 and 3.5 years postpartum
measure: LDL cholesterol in mg/dL from blood sample following overnight fast of at least 8 hours
timeFrame: Blood sample taken at study clinic visit between 2 and 3.5 years postpartum
measure: Triglycerides in mg/dL from blood sample following overnight fast of at least 8 hours
timeFrame: Blood sample taken at study clinic visit between 2 and 3.5 years postpartum
measure: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) from glucose and insulin measured from blood sample following overnight fast of at least 8 hours
timeFrame: Blood sample taken at study clinic visit between 2 and 3.5 years postpartum
measure: High sensitivity C-reactive protein (hs-CRP) in mg/L measured from blood sample following overnight fast of at least 8 hours
timeFrame: Taken at study clinic visit between 2 and 3.5 years postpartum
measure: Hemoglobin A1c (%) measured from blood sample following overnight fast of at least 8 hours
timeFrame: Taken at study clinic visit between 2 and 3.5 years postpartum
measure: Sleep disordered breathing, defined as apnea-hypopnea index (AHI) of 3 or more
timeFrame: Taken at study clinic visit between 2 and 3.5 years postpartum
Other outcomes:
measure: N-terminal of the Prohormone Brain Natriuretic peptide (NT-proBNP) in pg/mL from blood sample following overnight fast of at least 8 hours
timeFrame: Blood sample taken at study clinic visit between 2 and 3.5 years postpartum
Locations:
city: Fountain Valley
country: United States
facility: Fountain Valley Regional Hospital and Medical Center- UCI MFM private practice
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center, Women's and Children's Hospital - Women's Perinatal Group, OB Clinic
state: California
city: Orange
country: United States
facility: University of California, Irvine, Medical Center - Prenatal care clinics and private practice
state: California
city: Newark
country: United States
facility: Christiana Care Health Systems
state: Delaware
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine OB/GYN
state: Indiana
city: New York
country: United States
facility: Columbia University Medical Center- Department of OB/GYN Division of Maternal Fetal Medicine
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University, MetroHealth Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Womens Hospital
state: Pennsylvania
city: Ogden
country: United States
facility: McKay Dee Hospital
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
Study officials:
affiliation: University of Texas Medical Branch at Galveston
name: George Saade, M.D.
role: STUDY_CHAIR
affiliation: Case Western Reserve University
name: Brian M. Mercer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Ronald Wapner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: David M. Haas, M.D., M.S.,
role: PRINCIPAL_INVESTIGATOR
affiliation: Magee Womens Hospital - University of Pittsburgh
name: Hyagriv N. Simhan, MD, MSCR
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: William Grobman, M.D., M.B.A.
role: PRINCIPAL_INVESTIGATOR
affiliation: University CA Irvine
name: Judith Chung, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Samuel Parry, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Robert M. Silver, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haas DM, Ehrenthal DB, Koch MA, Catov JM, Barnes SE, Facco F, Parker CB, Mercer BM, Bairey-Merz CN, Silver RM, Wapner RJ, Simhan HN, Hoffman MK, Grobman WA, Greenland P, Wing DA, Saade GR, Parry S, Zee PC, Reddy UM, Pemberton VL, Burwen DR; National Heart, Lung, and Blood Institute nuMoM2b Heart Health Study Network. Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study. Am J Epidemiol. 2016 Mar 15;183(6):519-30. doi: 10.1093/aje/kwv309. Epub 2016 Jan 28.
citation: Catov JM, Parker CB, Gibbs BB, Bann CM, Carper B, Silver RM, Simhan HN, Parry S, Chung JH, Haas DM, Wapner RJ, Saade GR, Mercer BM, Bairey-Merz CN, Greenland P, Ehrenthal DB, Barnes SE, Shanks AL, Reddy UM, Grobman WA; NICHD NuMoM2b and NHLBI NuMoM2b Heart Health Study Network. Patterns of leisure-time physical activity across pregnancy and adverse pregnancy outcomes. Int J Behav Nutr Phys Act. 2018 Jul 11;15(1):68. doi: 10.1186/s12966-018-0701-5.
citation: Facco FL, Parker CB, Hunter S, Reid KJ, Zee PC, Silver RM, Haas DM, Chung JH, Pien GW, Nhan-Chang CL, Simhan HN, Parry S, Wapner RJ, Saade GR, Mercer BM, Torres C, Knight J, Reddy UM, Grobman WA; NICHD NuMoM2b and NHLBI NuMoM2b Heart Health Study Networks. Association of Adverse Pregnancy Outcomes With Self-Reported Measures of Sleep Duration and Timing in Women Who Are Nulliparous. J Clin Sleep Med. 2018 Dec 15;14(12):2047-2056. doi: 10.5664/jcsm.7534.
citation: Haas DM, Yang Z, Parker CB, Chung J, Parry S, Grobman WA, Mercer BM, Simhan HN, Silver RM, Wapner RJ, Saade GR, Greenland P, Merz NB, Reddy UM, Pemberton VL; nuMoM2b study and the nuMoM2b Heart Health Study. Factors associated with duration of breastfeeding in women giving birth for the first time. BMC Pregnancy Childbirth. 2022 Sep 22;22(1):722. doi: 10.1186/s12884-022-05038-7.
citation: Facco FL, Redline S, Hunter SM, Zee PC, Grobman WA, Silver RM, Louis JM, Pien GW, Mercer B, Chung JH, Bairey Merz CN, Haas DM, Nhan-Chang CL, Simhan HN, Schubert FP, Parry S, Reddy U, Saade GR, Hoffman MK, Levine LD, Wapner RJ, Catov JM, Parker CB. Sleep-disordered Breathing in Pregnancy and after Delivery: Associations with Cardiometabolic Health. Am J Respir Crit Care Med. 2022 May 15;205(10):1202-1213. doi: 10.1164/rccm.202104-0971OC.
citation: Hawkins M, Parker CB, Redline S, Larkin JC, Zee PP, Grobman WA, Silver RM, Louis JM, Pien GW, Basner RC, Chung JH, Haas DM, Nhan-Chang CL, Simhan HN, Blue NR, Parry S, Reddy U, Facco F; NICHD NuMoM2b and NHLBI NuMoM2b Heart Health Study Networks. Objectively assessed sleep-disordered breathing during pregnancy and infant birthweight. Sleep Med. 2021 May;81:312-318. doi: 10.1016/j.sleep.2021.02.043. Epub 2021 Feb 27.
citation: Catov JM, McNeil RB, Marsh DJ, Mercer BM, Bairey Merz CN, Parker CB, Pemberton VL, Saade GR, Chen YI, Chung JH, Ehrenthal DB, Grobman WA, Haas DM, Parry S, Polito L, Reddy UM, Silver RM, Simhan HN, Wapner RJ, Kominiarek M, Kreutz R, Levine LD, Greenland P; NHLBI nuMoM2b Heart Health Study. Early Pregnancy Atherogenic Profile in a First Pregnancy and Hypertension Risk 2 to 7 Years After Delivery. J Am Heart Assoc. 2021 Feb;10(5):e017216. doi: 10.1161/JAHA.120.017216. Epub 2021 Feb 23.
citation: Haas DM, Parker CB, Marsh DJ, Grobman WA, Ehrenthal DB, Greenland P, Bairey Merz CN, Pemberton VL, Silver RM, Barnes S, McNeil RB, Cleary K, Reddy UM, Chung JH, Parry S, Theilen LH, Blumenthal EA, Levine LD, Mercer BM, Simhan H, Polito L, Wapner RJ, Catov J, Chen I, Saade GR; NHLBI nuMoM2b Heart Health Study. Association of Adverse Pregnancy Outcomes With Hypertension 2 to 7 Years Postpartum. J Am Heart Assoc. 2019 Oct;8(19):e013092. doi: 10.1161/JAHA.119.013092. Epub 2019 Sep 30.
citation: Monk C, Webster RS, McNeil RB, Parker CB, Catov JM, Greenland P, Bairey Merz CN, Silver RM, Simhan HN, Ehrenthal DB, Chung JH, Haas DM, Mercer BM, Parry S, Polito L, Reddy UM, Saade GR, Grobman WA; NICHD nuMoM2b and NHLBI nuMoM2b Heart Health Study Networks. Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery. Arch Womens Ment Health. 2020 Jun;23(3):361-369. doi: 10.1007/s00737-019-00970-8. Epub 2019 Jun 29.