TY - JOUR

T1 - Time to pregnancy and life expectancy

T2 - a cohort study of 18796 pregnant couples

AU - Lindahl-Jacobsen, R.

AU - Petersson, M. Tavlo

AU - Priskorn, L.

AU - Skakkebæk, N. E.

AU - Juul, A.

AU - Kristensen, D. M.

AU - Eisenberg, M. L.

AU - Jensen, T. K.

N1 - Publisher Copyright: © 2024 Oxford University Press. All rights reserved.

PY - 2024

Y1 - 2024

N2 - STUDY QUESTION: Is fecundity, measured as time to pregnancy (TTP), associated with mortality in parents? SUMMARY ANSWER: Prolonged TTP is associated with increased mortality in both mothers and fathers in a dose–response manner. WHAT IS KNOWN ALREADY: Several studies have linked both male and female fecundity to mortality. In women, infertility has been linked to several diseases, but studies suggest that the underlying conditions, rather than infertility, increase mortality. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out on 18 796 pregnant couples, in which the pregnant women attended prophylactic antenatal care between 1973 and 1987 at a primary and tertiary care unit. The couples were followed in Danish mortality registers from their child’s birth date until death or until 2018. The follow-up period was up to 47 years, and there was complete follow-up until death, emigration or end of study. PARTICIPANTS/MATERIALS, SETTING, METHODS: At the first antenatal visit, the pregnant women were asked to report the time to the current pregnancy. Inclusion was restricted to the first pregnancy, and TTP was categorised into <12 months, ≥12 months, not planned, and not available. In sub-analyses, TTP ≥12 was further categorized into 12–35, 36–60, and >60 months. Information for parents was linked to several Danish nationwide health registries. Survival analysis was used to estimate the hazard ratios (HRs) with a 95% CI for survival and adjusted for age at the first attempt to become pregnant, year of birth, socioeconomic status, mother’s smoking during pregnancy, and mother’s BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Mothers and fathers with TTP >60 months survived, respectively, 3.5 (95% CI: 2.6–4.3) and 2.7 (95% CI: 1.8–3.7) years shorter than parents with a TTP <12 months. The mortality was higher for fathers (HR: 1.21, 95% CI: 1.09–1.34) and mothers (HR: 1.29, 95% CI: 1.12–1.49) with TTP ≥12 months compared to parents with TTP <12 months. The risk of all-cause mortality during the study period increased in a dose–response manner with the highest adjusted HR of 1.98 (95% CI: 1.62–2.41) for fathers and 2.03 (95% CI: 1.56–2.63) for mothers with TTP >60 months. Prolonged TTP was associated with several different causes of death in both fathers and mothers, indicating that the underlying causes of the relation between fecundity and survival may be multi-factorial. LIMITATIONS, REASONS FOR CAUTION: A limitation is that fecundity is measured using a pregnancy-based approach. Thus, the cohort is conditioned on fertility success and excludes sterile couples, unsuccessful attempts and spontaneous abortions. The question used to measure TTP when the pregnant woman was interviewed at her first attended prophylactic antenatal care: ‘From the time you wanted a pregnancy until it occurred, how much time passed?’ could potentially have led to serious misclassification if the woman did not answer on time starting unprotected intercourse but on the start of wishing to have a child. WIDER IMPLICATIONS OF THE FINDINGS: We found that TTP is a strong marker of survival, contributing to the still-emerging evidence that fecundity in men and women reflects their health and survival potential. STUDY FUNDING/COMPETING INTEREST(S): The authors acknowledge an unrestricted grant from Ferring. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. M.L.E. is an advisor to Ro, VSeat, Doveras, and Next.

AB - STUDY QUESTION: Is fecundity, measured as time to pregnancy (TTP), associated with mortality in parents? SUMMARY ANSWER: Prolonged TTP is associated with increased mortality in both mothers and fathers in a dose–response manner. WHAT IS KNOWN ALREADY: Several studies have linked both male and female fecundity to mortality. In women, infertility has been linked to several diseases, but studies suggest that the underlying conditions, rather than infertility, increase mortality. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out on 18 796 pregnant couples, in which the pregnant women attended prophylactic antenatal care between 1973 and 1987 at a primary and tertiary care unit. The couples were followed in Danish mortality registers from their child’s birth date until death or until 2018. The follow-up period was up to 47 years, and there was complete follow-up until death, emigration or end of study. PARTICIPANTS/MATERIALS, SETTING, METHODS: At the first antenatal visit, the pregnant women were asked to report the time to the current pregnancy. Inclusion was restricted to the first pregnancy, and TTP was categorised into <12 months, ≥12 months, not planned, and not available. In sub-analyses, TTP ≥12 was further categorized into 12–35, 36–60, and >60 months. Information for parents was linked to several Danish nationwide health registries. Survival analysis was used to estimate the hazard ratios (HRs) with a 95% CI for survival and adjusted for age at the first attempt to become pregnant, year of birth, socioeconomic status, mother’s smoking during pregnancy, and mother’s BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Mothers and fathers with TTP >60 months survived, respectively, 3.5 (95% CI: 2.6–4.3) and 2.7 (95% CI: 1.8–3.7) years shorter than parents with a TTP <12 months. The mortality was higher for fathers (HR: 1.21, 95% CI: 1.09–1.34) and mothers (HR: 1.29, 95% CI: 1.12–1.49) with TTP ≥12 months compared to parents with TTP <12 months. The risk of all-cause mortality during the study period increased in a dose–response manner with the highest adjusted HR of 1.98 (95% CI: 1.62–2.41) for fathers and 2.03 (95% CI: 1.56–2.63) for mothers with TTP >60 months. Prolonged TTP was associated with several different causes of death in both fathers and mothers, indicating that the underlying causes of the relation between fecundity and survival may be multi-factorial. LIMITATIONS, REASONS FOR CAUTION: A limitation is that fecundity is measured using a pregnancy-based approach. Thus, the cohort is conditioned on fertility success and excludes sterile couples, unsuccessful attempts and spontaneous abortions. The question used to measure TTP when the pregnant woman was interviewed at her first attended prophylactic antenatal care: ‘From the time you wanted a pregnancy until it occurred, how much time passed?’ could potentially have led to serious misclassification if the woman did not answer on time starting unprotected intercourse but on the start of wishing to have a child. WIDER IMPLICATIONS OF THE FINDINGS: We found that TTP is a strong marker of survival, contributing to the still-emerging evidence that fecundity in men and women reflects their health and survival potential. STUDY FUNDING/COMPETING INTEREST(S): The authors acknowledge an unrestricted grant from Ferring. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. M.L.E. is an advisor to Ro, VSeat, Doveras, and Next.

KW - causes of death

KW - fecundity

KW - fertility

KW - life expectancy

KW - mortality

KW - reproduction

KW - survival

KW - time to pregnancy

U2 - 10.1093/humrep/dead260

DO - 10.1093/humrep/dead260

M3 - Journal article

C2 - 38115232

AN - SCOPUS:85186349907

VL - 39

SP - 595

EP - 603

JO - Human reproduction (Oxford, England)

JF - Human reproduction (Oxford, England)

SN - 0268-1161

IS - 3

ER -