Intergenerational Occurrence of Premature Birth and Reproductive Health in Prematurely-Born Women in the Women's Health Initiative.

OBJECTIVE: To compare reproductive history and postmenopausal health by birth status (preterm vs. full term) in a U.S. longitudinal study of postmenopausal women. Birth status was examined according to region of residence, household, and neighborhood socioeconomic status (SES). METHODS: In the Women's Health Initiative Observational Study, 2271 women were born prematurely (< 37 weeks). ANOVA and Chi-square determined birth status differences of reproductive history, pregnancy, and postmenopausal health. Odds ratios were calculated using either binary logistic or multinomial logistic regression. SES and U.S. region of residence were examined as potential effect modifiers. RESULTS: Preterm-born women compared to term-born women had higher risk of delivering a premature infant (aOR 1.68, 95% CI [1.46, 1.93]), higher odds of later-age first pregnancy (aOR 1.27 95% CI [1.02, 1.58]), longer duration to become pregnant (> 1 year to pregnancy) (aOR 1.10 95% CI [1.01, 1.21]), more miscarriages (aOR 1.23 95% CI [1.11, 1.37]), and more pregnancy complications including hypertension (aOR 1.58 95% CI (1.13, 2.21)], preeclampsia (aOR 1.64 95% CI [1.24, 2.16]), and gestational diabetes (aOR 1.68 95% CI [1.11, 2.53]). Preterm-born women had higher odds of menopause before age 50 (aOR 1.09 95% CI [1.05, 1.14]). Post-menopause, they had higher rates of diabetes (p = .01), hypertension (p = .01), hysterectomy (p = .045), and higher Charlson Comorbidity Index scores (p = .01). CONCLUSIONS: Preterm-born women had higher reproductive and pregnancy risks which when coupled with early menopause, may indicate a shorter childbearing period than term-born women. Guidelines for integration of preterm history in women's health care across the life course are needed to identify and manage their higher risk.

The co-occurrence and cumulative prevalence of hypertension, rheumatoid arthritis, and hypothyroidism in preterm-born women in the Women's Health Initiative.

Emerging evidence suggests that preterm-born individuals (<37 weeks gestation) are at increased risk of developing chronic health conditions in adulthood. This study compared the prevalence, co-occurrence, and cumulative prevalence of three female predominant chronic health conditions - hypertension, rheumatoid arthritis [RA], and hypothyroidism - alone and concurrently. Of 82,514 U.S. women aged 50-79 years enrolled in the Women's Health Initiative, 2,303 self-reported being born preterm. Logistic regression was used to analyze the prevalence of each condition at enrollment with birth status (preterm, full term). Multinomial logistic regression models analyzed the association between birth status and each condition alone and concurrently. Outcome variables using the 3 conditions were created to give 8 categories ranging from no disease, each condition alone, two-way combinations, to having all three conditions. The models adjusted for age, race/ethnicity, and sociodemographic, lifestyle, and other health-related risk factors. Women born preterm were significantly more likely to have any one or a combination of the selected conditions. In fully adjusted models for individual conditions, the adjusted odds ratios (aORs) were 1.14 (95% CI, 1.04, 1.26) for hypertension, 1.28 (1.12, 1.47) for RA, and 1.12 (1.01, 1.24) for hypothyroidism. Hypothyroidism and RA were the strongest coexisting conditions [aOR 1.69, 95% CI (1.14, 2.51)], followed by hypertension and RA [aOR 1.48, 95% CI (1.20, 1.82)]. The aOR for all three conditions was 1.69 (1.22, 2.35). Perinatal history is pertinent across the life course. Preventive measures and early identification of risk factors and disease in preterm-born individuals are essential to mitigating adverse health outcomes in adulthood.

Association of Preterm Birth With Prevalent and Incident Hypertension, Early-Onset Hypertension, and Cardiovascular Disease in the Women's Health Initiative.

Increasing evidence suggests preterm birth is a risk factor for hypertension and cardiovascular disease (CVD) in adulthood. Whether there is effect modification by hypertension on CVD risk is unknown. To investigate the associations between preterm birth, hypertension, and incident CVD, we identified 2,303 women aged 50 to 79 years who self-reported being born preterm from the Women's Health Initiative. Using multivariable logistic regression, prevalent hypertension at enrollment, age at hypertension diagnosis, and antihypertensive medication use were compared by birth status (preterm, full-term). Risk of incident hypertension, coronary heart disease, and CVD were analyzed using multivariable Cox proportional-hazard models. Both models adjusted for age, race/ethnicity, education, smoking, physical activity, body mass index, and diabetes mellitus. Significant associations were found between preterm birth and prevalent hypertension (37% vs 33.1%; adjusted odds ratio 1.26 [95% confidence interval (CI) 1.15 to 1.28] p = <0.0001), early-onset hypertension (<50 years) (14.7% vs 11.7%; adjusted odds ratio 1.31, 95% CI 1.15 to 1.48, p = <0.0001), and incident hypertension (53.2% vs 51%; ajusted hazard ratio 1.10, 95% CI 1.03 to 1.19, p = 0.008). Preterm-born women reported taking more antihypertensive medications (2.9% vs 2.6%, p = 0.04). Preterm birth had a nonsignificant association with CVD risk, but when stratified by prevalent hypertension, women born preterm without hypertension had elevated CVD risk compared with women born full-term without prevalent hypertension. Women with prevalent hypertension, preterm and full-term, had similar magnitudes of elevations in CVD risk. In conclusion, preterm birth increases the risk of hypertension and coronary heart disease. With 10% of the population born preterm, birth history should be assessed as a CVD risk factor.

A new cardiovascular disease risk factor for young adults: Preterm birth.

ABSTRACT: Adults born preterm (birth <37 weeks' gestation) have a two-fold increased risk of early cardiovascular mortality. With 10% of the U.S. population born prematurely and perinatal advancements dramatically improving survival rates, millions of survivors are now reaching adulthood. This phenomenon has introduced a whole new population of individuals with a history of preterm birth. Although the prevailing notion has been that preterm birth is a condition confined only to infancy and early childhood, we now know preterm birth is a risk for lifelong chronic health conditions. Despite almost a decade of epidemiological evidence showing increased cardiovascular risk for those born preterm, this has not yet been translated into clinical practice. As a result, clinicians are caring for adults born prematurely without screening and treatment guidelines for this at-risk population and few inquire about birth history during clinical encounters. This brief report presents growing evidence about disrupted cardiogenesis and consequential structural and functional modifications. By asking the question "Were you born preterm?," nurse practitioners can take the first step of increasing their awareness of this at-risk population and mitigate adverse cardiovascular outcomes by using preterm birth as a risk factor when determining health promotion and treatment decisions.

A Protocol to Assess Adult Outcomes at 30 Years Following Preterm Birth.

BACKGROUND: Among the most intense adversity experiences for infants is premature birth. Early birth marks the beginning of a life course that broadly affects families, healthcare, education, social systems, and the survivors themselves. For many, the transition to adulthood is challenging and often hampered by cognitive, physical and mental health, and motor and independence difficulties. OBJECTIVES: The aim of this study was to share a comprehensive protocol of a 10th follow-up study of premature infants in their 30s. The protocol accounts for stress during the neonatal period, the cumulative context (risk and protection) of development, biological and epigenetic mechanisms, and individual resilience. METHODS: The prospective, five-group longitudinal design includes 215 term-born and preterm-born individuals with various neonatal morbidities at ages 30-35 years. Adult outcomes include health, adaptive, executive function, work, and social competence. Novel measures are four system indicators of allostatic load (AL) and epigenetics. Contextual measures include socioeconomic risk and individual resilience. All measures were selected based on coherence with constructs of the scientific aims, strong psychometrics, continuity for repeated measures, and minimal subject burden. Objective assessments include body composition imaging, exercise testing, blood and saliva collection, and actigraphy. The two-phase protocol takes approximately 8 hours. DISCUSSION: After an 11-month COVID-19 pause, participant response has been strong. As of May 2022, 75 participants have completed the full protocol, and 99 have consented to participate. When socioeconomic risk is controlled, we hypothesize that life course trajectories in physical and psychological health, adaptive function, and executive function will differ between term and preterm neonatal morbidity groups. AL will vary across groups and contribute to outcomes. We expect proximal protection and resilience to mediate the cumulative medical and socioeconomic risk and AL. Epigenome-wide DNA methylation, with estimates of age acceleration, will be examined across groups and explored in longitudinal associations with medical risk, socioeconomic status, and protection. To our knowledge, this is the only U.S. study of premature infants aged 30-35 years. With millions of preterm-born individuals reaching adulthood, the protocol incorporates molecular and genetic biomarkers in a life course developmental examination to inform the timing and content of interventions.