Postpartum psychiatric disorders and subsequent live birth: a population-based cohort study in Denmark.

STUDY QUESTION: Are women with a history of first-onset postpartum psychiatric disorders after their first liveborn delivery less likely to have a subsequent live birth? SUMMARY ANSWER: Women with incident postpartum psychiatric disorders are less likely to go on to have further children. WHAT IS KNOWN ALREADY: Women are particularly vulnerable to psychiatric disorders in the postpartum period. The potential effects of postpartum psychiatric disorders on the mother's future chances of live birth are so far under-researched. STUDY DESIGN, SIZE, DURATION: A population-based cohort study consisted of 414 571 women who had their first live birth during 1997-2015. We followed the women for a maximum of 19.5 years from the date of the first liveborn delivery until the next conception leading to a live birth, emigration, death, their 45th birthday or 30 June 2016, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postpartum psychiatric disorders were defined as filling a prescription for psychotropic medications or hospital contact for psychiatric disorders for the first time within 6 months postpartum. The outcome of interest was time to the next conception leading to live birth after the first liveborn delivery. Records on the death of a child were obtained through the Danish Register of Causes of Death. Cox regression was used to estimate the hazard ratios (HRs), stratified by the survival status of the first child. MAIN RESULTS AND THE ROLE OF CHANCE: Altogether, 4327 (1.0%) women experienced postpartum psychiatric disorders after their first liveborn delivery. The probability of having a subsequent live birth was 69.1% (95% CI: 67.4-70.7%) among women with, and 82.3% (95% CI: 82.1-82.4%) among those without, postpartum psychiatric disorders. Women with postpartum psychiatric disorders had a 33% reduction in the rate of having second live birth (HR = 0.67, 95% CI: 0.64-0.69), compared to women without postpartum psychiatric disorders. The association disappeared if the first child died (HR = 1.01, 95% CI: 0.85-1.20). If postpartum psychiatric disorders required hospitalisations, this was associated with a more pronounced reduction in live birth rate, irrespective of the survival status of the first child (HR = 0.54, 95% CI: 0.47-0.61 if the first child survived, and HR = 0.49, 95% CI: 0.23-1.04 if the first child died). LIMITATIONS, REASONS FOR CAUTION: The use of population-based registers allows for the inclusion of a representative cohort with almost complete follow-up. The large sample size enables us to perform detailed analyses, accounting for the survival status of the child. However, we did not have accurate information on stillbirths and miscarriages, and only pregnancies that led to live birth were included. WIDE IMPLICATIONS OF THE FINDINGS: Our study is the first study to investigate subsequent live birth after postpartum psychiatric disorders in a large representative population. The current study indicates that postpartum psychiatric disorders have a significant impact on subsequent live birth, as women experiencing these disorders have a decreased likelihood of having more children. However, the variations in subsequent live birth rate are influenced by both the severity of the disorders and the survival status of the first-born child, indicating that both personal choices and decreased fertility may have a role in the reduced subsequent live birth rate among women with postpartum psychiatric disorders. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Danish Council for Independent Research (DFF-5053-00156B), the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 837180, AUFF NOVA (AUFF-E 2016-9-25), iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (R155-2014-1724), Niels Bohr Professorship Grant from the Danish National Research Foundation and the Stanley Medical Research Institute, the National Institute of Mental Health (NIMH) (R01MH104468) and Fabrikant Vilhelm Pedersen og Hustrus Legat. The authors do not declare any conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal bereavement in the antenatal period and oral cleft in the offspring.

STUDY QUESTION: Is maternal bereavement (emotional stress) due to loss of a close relative in the antenatal period associated with the risk of oral cleft in the offspring? SUMMARY ANSWER: Our study suggests prenatal maternal bereavement is associated with an increased risk of oral cleft in the offspring, especially when the bereavement was due to a sudden death or death of a child. WHAT IS KNOWN ALREADY: The aetiology of oral cleft is unknown but includes both genetic and environmental causes. STUDY DESIGN, SIZE AND DURATION: We performed a population-based cohort study based on several national registers in Denmark from 1978 to 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our final study population consisted of 1 771 663 children. Of these 35 118 (2%) were born to mothers who experienced bereavement in the exposure window from 1 year before pregnancy to the end of the first trimester. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 3043 children were diagnosed with a cleft; 968 with cleft lip, 1206 with cleft lip and palate and 869 with a cleft palate. For overall bereavement the prevalence was 1.7 per 1 000 live born in the unexposed children and 2.2 per 1 000 live born in the exposed children. Overall, maternal bereavement due to the death of a close relative from 1 year before conception to the end of the first trimester was associated with a significantly increased risk of oral cleft [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.01; 1.61). When mothers lost a relative due to a sudden death, the risk of oral cleft in the offspring was higher (OR: 1.76, 95% CI: 1.06; 2.94). Losing a relative in the time period before pregnancy and during the first trimester showed a tendency to an increased risk. The risk increase was 77% when the mother was bereaved due to sudden death and the estimation was robust in different analytical strategies. LIMITATIONS, REASONS FOR CAUTION: It is a limitation that we only studied live born children, but most children with isolated oral cleft would survive their pregnancy and birth. Since oral cleft are rare and despite the large study population, we still had a relatively small number of cases, which results in limited power to detect small differences. We did not have actual measurements of the maternal cortisol concentration, but we believe that bereavement due to death of a close relative produces a strong stress reaction in most people. Also we did not have the opportunity to adjust for intake of folic acid and use of anti-depressant; however, analysis in a subset of the data showed no difference in these intakes between exposed and unexposed mothers. WIDER IMPLICATIONS OF THE FINDINGS: With this study we add a large-scale human cohort study to the body of literature on stress and birth defects. Our study is in agreement with previously published results and can be generalized to similar populations like the native Danish population. Severe stress may be added to the list of potential causes for oral cleft.