Fertility of Adults Born Very Preterm or With Very Low Birth Weight

Abstract

Importance: Contradictory differences regarding fertility among adults born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW; <1500 g) have been reported at different ages. Longitudinal investigations of fertility beyond ages 20 to 29 years are lacking.

Objective: To assess whether VP and VLBW are associated with lower fertility up to age 35 years.

Design, setting, and participants: This prospective population-based cohort study was conducted in Bavaria, Germany, with participants born between January 1985 and March 1986 who required admission to a children's hospital within the first 10 days after birth. Healthy infants born at term (ie, at least 37 weeks' gestation) in the same hospital and children alive at 6 years were selected as controls. Follow-up occurred repeatedly up to 34 to 35 years. Data were analyzed from July to December 2024.

Exposures: Gestational age and birth weight.

Main outcomes and measures: Cumulative incidence of having the first alive child (ie, fertility) was calculated using Kaplan-Meier estimation and the difference between participants born VP or with VLBW and term-born participants was compared with log-rank tests. Univariable and hierarchical multivariable Cox proportional hazards regressions were performed to estimate hazard ratios (HRs) for fertility associated with VP and VLBW adjusting for individual factors. Estimations were compared between early (<30 years) and late (≥30 years) reproductive windows.

Results: A total of 414 participants (212 born VP or with VLBW and 202 term-born) were included (mean [SD] age, 34.67 [0.53] years; 216 [52.2%] female). Cumulative incidence of having the first alive child was lower in participants born VP or with VLBW throughout the follow-up. The association of VP and VLBW with lower fertility was significant during the late (HR, 0.46; 95% CI, 0.31-0.68) but not early (HR, 0.73; 95% CI, 0.47-1.14) reproductive window; this association attenuated after adjusting for neonatal factors (sex and family socioeconomic status) and childhood neurosensory impairment at step 2 (HR, 0.59; 95% CI 0.40-0.88), childhood family factors (eg, parenting) at step 3 (HR, 0.61; 95% CI, 0.40-0.92), and there was no longer an association after adjusting for sociodemographic factors (eg, partnering) at step 4 (HR, 0.78; 95% CI, 0.50-1.20). Partnering (ie, being married or cohabitating with a partner) had the largest magnitude association with fertility across both the early (HR, 7.87; 95% CI, 3.44-18.00) and late (HR, 3.95; 95% CI, 2.47-6.31) reproductive windows.

Conclusions and relevance: In this cohort study of participants born VP or with VLBW and term-born adults, VP and VLBW were associated with overall lower fertility. A major reason was an association of less partnering with lower fertility, suggesting that partnering is key to reproductive success.

Figure 1.. Participant Flowchart

Flowchart describes eligible sample and those lost to follow-up among participants born very preterm or with very low birth weight (VP/VLBW) and term-born participants at 34-year assessment.

Figure 2.. Cumulative Incidence of Having the First Alive Child

The figure shows cumulative incidence of having the first alive child in participants born very preterm (VP) or with very low birth weight (VLBW) and term-born participants during the overall (A), early (B), and late (C) reproductive windows.

Figure 3.. Association of Fertility With Being Born Very Preterm or With Very Low Birth Weight (VP/VLBW)

The figure shows hazard ratios (HRs) and 95% CIs at each step of the hierarchical multivariable Cox proportional hazards regression models during the overall (A), early (B), and late (C) reproductive windows. NSI indicates neurosensory impairment.