# Preterm birth and long-term risk of cardiovascular disease in mothers and offspring

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $664,798

## Abstract

Currently about 1 of every 10 births in the US occurs preterm (gestational age <37 completed weeks), and
because of advances in treatment, >95% of preterm infants survive to adulthood. Recent research has shown
that both the mothers and offspring of preterm birth (PTB) have higher long-term risks of metabolic syndrome,
a major risk factor for cardiovascular disease (CVD). Mothers who deliver preterm may also have higher long-
term CVD incidence; however, the reported risks of CVD in adult offspring of PTB have been conflicting. A
recent Trans-NIH Working Group highlighted a pressing need for studies that: (1) stratify long-term CVD risks
by PTB subtype (e.g., spontaneous vs. indicated due to maternal/fetal conditions) to help elucidate underlying
mechanisms and tailor long-term patient care; (2) allow longer follow-up into mid-adulthood or later when
disease risks remain poorly understood; and (3) include large sample sizes to allow examination of long-term
outcomes with high statistical power. We hypothesize that: (1) PTB is associated with higher long-term risks
of CVD (i.e., ischemic heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, aortic
disease) among mothers and adult offspring, with increasing dose-response relationships by earlier gestational
age; and (2) These associations exist for all major types of PTB, but are stronger for those related to placental
insufficiency (e.g., preeclampsia or diabetes), which is associated with oxidative stress and inflammation,
leading to structural microvascular changes. To address these hypotheses, we propose to conduct the first
comprehensive examination of PTB and its subtypes in relation to CVD risks among mothers and their adult
offspring. We will assemble and analyze national databases containing all ~2.3 million births to ~1.2 million
mothers in Sweden during 1973-1995 and all inpatient and outpatient diagnoses of CVD through 2015. Our
specific aims are to: (1) Examine PTB and its subtypes in relation to long-term risks of CVD and CVD-related
outcomes (hypertension, diabetes, sleep apnea) in mothers and adult offspring; (2) determine if there are
sociodemographic subgroups that are more susceptible to PTB effects on long-term risks; and (3) explore
potential confounding effects of unmeasured familial (genetic and shared environmental) factors on PTB-CVD
associations using co-relative analyses. The proposed research is significant because PTB is common and
unprecedented numbers of survivors are now reaching adulthood (~400,000/year in the US); thus even
modestly increased long-term risks translate into a large population health burden. It is innovative because it
will provide the first comprehensive examination of PTB and its subtypes in relation to CVD risks, and use a
co-relative design to disentangle familial confounding. It is highly cost-efficient because we will assemble
these data from national registries that are unavailable or prohibitively costly to colle...

## Key facts

- **NIH application ID:** 10155552
- **Project number:** 5R01HL139536-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Casey Crump
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $664,798
- **Award type:** 5
- **Project period:** 2018-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155552

## Citation

> US National Institutes of Health, RePORTER application 10155552, Preterm birth and long-term risk of cardiovascular disease in mothers and offspring (5R01HL139536-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155552. Licensed CC0.

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