Parents' age at birth and daughters' time to pregnancy: a study within the Norwegian Mother, Father and Child Cohort.

STUDY QUESTION: Is parents' age at birth associated with daughters' fecundability? SUMMARY ANSWER: Daughters born to mothers <25 years or fathers ≥35 years had slightly lower fecundability. WHAT IS KNOWN ALREADY: Two recent studies reported lower fecundability in women born to mothers <20 years, which may be partly due to daughters of young mothers being less likely to plan their pregnancies. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 58 496 pregnancy planners (4290 of whom conceived with treatment) and 14 194 non-planners enrolled in the Norwegian Mother, Father and Child Cohort Study (MoBa) between 2000 and 2008, linked with the Medical Birth Registry of Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were born in Norway between 1967 and 1990. We estimated fecundability ratios (FRs) and 95% CI as a function of both parents' (F1) age at the daughter's (F2) birth among non-treated planners and the relative risk of time to pregnancy (TTP) ≥12 months or treatment among all planners. We explored whether daughters of young mothers were under-represented among planners, compared with the underlying population. Finally, we estimated FRs after adding non-planners, randomly assigned to conceiving in the first cycle with probabilities of 0.60 and 0.70. MAIN RESULTS AND THE ROLE OF CHANCE: For both mother and father, the reference category was 25-29 years. Fecundability was slightly lower among daughters of older fathers (FRs (95% CI): 0.95 (0.92, 0.98) for F1 father's age 35-39 years and 0.93 (0.89, 0.97) for ≥40 years) and daughters of young mothers (0.92 (0.89, 0.96) for F1 mother's age <20 years and 0.97 (0.95, 0.99) for 20-24 years). Results were similar for the composite outcome TTP ≥ 12 months or treatment, although driven by TTP ≥ 12. Compared with Norwegian-born women with ≥1 pregnancy, planners born to mothers <20 years were underrepresented. Including non-planners with very high fecundability weakened the association with mother's age <20 years. LIMITATIONS, REASONS FOR CAUTION: This was a pregnancy cohort with retrospectively reported information on planning and TTP. Selection bias appears unlikely to fully explain the association with mother's age <20 years. WIDER IMPLICATIONS OF THE FINDINGS: Daughters of young mothers or older fathers may have slightly lower fecundability. If corroborated, the finding about older paternal age is relevant, given the widespread tendency to delay childbearing. STUDY FUNDING/COMPETING INTEREST(S): This work was partly funded by the Research Council of Norway (project no. 320656), and through its Centres of Excellence funding scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 947684). No competing interests. TRIAL REGISTRATION NUMBER: N/A.

The association between miscarriage and fecundability: the Norwegian Mother, Father and Child Cohort Study.

STUDY QUESTION: Is fecundability associated with miscarriage history and future miscarriage risk? SUMMARY ANSWER: Prior miscarriage was associated with lower fecundability, and participants with a history of subfertility (time-to-pregnancy (TTP) ≥12 months) were at a higher risk of subsequent miscarriage. WHAT IS KNOWN ALREADY: Although miscarriage and low fecundability share common risk factors, prior studies have reported both lower and higher fecundability after miscarriage. STUDY DESIGN, SIZE, DURATION: In this study, we examined two related associations: one, between miscarriage history and subsequent fecundability and, two, between fecundability and miscarriage risk in the subsequent pregnancy. The study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). In addition, the outcome of the pregnancy after the MoBa index pregnancy was obtained by linking information from three national health registries: the Medical Birth Registry of Norway, the Norwegian Patient Registry and the general practice database. PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined the association between number of prior miscarriages and fecundability in 48 537 naturally conceived, planned pregnancies in participants with at least one prior pregnancy. We estimated fecundability ratios (FRs) and 95% CIs using proportional probability regression. We further estimated the relative risk (RR) of miscarriage in the subsequent pregnancy as a function of TTP in the MoBa index pregnancy for 7889 pregnancies using log-binomial regression. Multivariable analyses adjusted for maternal age, pre-pregnancy maternal BMI, smoking status, cycle regularity, income level and highest completed or ongoing education. MAIN RESULTS AND THE ROLE OF CHANCE: Fecundability decreased as the number of prior miscarriages increased. The adjusted FRs among women with one, two and three or more prior miscarriages were 0.83 (95% CI: 0.80-0.85), 0.79 (95% CI: 0.74-0.83) and 0.74 (95% CI: 0.67-0.82), respectively, compared with women with no prior miscarriages. Compared to women with a TTP of <3 months, the adjusted RR of miscarriage in the subsequent pregnancy was 1.16 (0.99-1.35) with TTP of 3-6 months, 1.18 (0.93-1.49) with TTP of 7-11 months and 1.43 (1.13-1.81) with TTP of 12 or more months. LIMITATIONS, REASONS FOR CAUTION: Information on TTP and prior miscarriages was obtained retrospectively, and TTP was self-reported. MoBa is a pregnancy cohort, and findings may not be generalizable to all women. We were unable to examine the effect of changing partners between pregnancies, as well as other paternal factors such as seminal parameters. We also did not know what proportion of our participants had changed partners between their prior pregnancies and the index pregnancy. Furthermore, it is likely that many early miscarriages are not recognized. WIDER IMPLICATIONS OF THE FINDINGS: The association between miscarriage and fecundability may reflect a contribution of occult pregnancy losses to TTP, as well as shared underlying causes for reduced fecundability and miscarriage. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Research Council of Norway through its Medical Student Research Program funding scheme (project number 271555/F20), its Centres of Excellence funding scheme (project number 262700) and through the project 'Women's fertility - an essential component of health and well-being' (project number 320656). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). A.J.W. is supported by the Intramural Program of the National Institute of Environmental Health Sciences at the National Institutes of Health, USA. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.