Metabolism during pregnancy is a dynamic and precisely programmed process, the failure of which can bring devastating consequences to the mother and fetus. To define a high-resolution temporal profile of metabolites during healthy pregnancy, we analyzed the untargeted metabolome of 784 weekly blood samples from 30 pregnant women. Broad changes and a highly choreographed profile were revealed: 4,995 metabolic features (of 9,651 total), 460 annotated compounds (of 687 total), and 34 human metabolic pathways (of 48 total) were significantly changed during pregnancy. Using linear models, we built a metabolic clock with five metabolites that time gestational age in high accordance with ultrasound (R = 0.92). Furthermore, two to three metabolites can identify when labor occurs (time to delivery within two, four, and eight weeks, AUROC R 0.85). Our study represents a weekly characterization of the human pregnancy metabolome, providing a high-resolution landscape for understanding pregnancy with potential clinical utilities. ll

BackgroundSome 5%–15% of all women experience postpartum depression (PPD), which for many is their first psychiatric disorder. The purpose of this study was to estimate the incidence of postpartum affective disorder (AD), duration of treatment, and rate of subsequent postpartum AD and other affective episodes in a nationwide cohort of women with no prior psychiatric history.Methods and findingsLinking information from several Danish national registers, we constructed a cohort of 457,317 primiparous mothers with first birth (and subsequent births) from 1 January 1996 to 31 December 2013 (a total of 789,068 births) and no prior psychiatric hospital contacts and/or use of antidepressants. These women were followed from 1 January 1996 to 31 December 2014. Postpartum AD was defined as use of antidepressants and/or hospital contact for PPD within 6 months after childbirth. The main outcome measures were risk of postpartum AD, duration of treatment, and recurrence risk. We observed 4,550 (0.6%) postpartum episodes of AD. The analyses of treatment duration showed that 1 year after the initiation of treatment for their first episode, 27.9% of women were still in treatment; after 4 years, 5.4%. The recurrence risk of postpartum AD for women with a PPD hospital contact after first birth was 55.4 per 100 person-years; for women with postpartum antidepressant medication after first birth, it was 35.0 per 100 person-years. The rate of postpartum AD after second birth for women with no history of postpartum AD was 1.2 per 100 person-years. After adjusting for year of birth and mother’s age, women with PPD hospital contact after first birth had a 46.4 times higher rate (95% CI 31.5–68.4) and women with postpartum antidepressant medication after their first birth had a 26.9 times higher rate (95% CI 21.9–33.2) of a recurrent postpartum episode after their second birth compared to women with no postpartum AD history. Limitations include the use of registry data to identify cases and limited confounder control.ConclusionsIn this study, an episode of postpartum AD was observed for 0.6% of childbirths among women with no prior psychiatric history. The observed episodes were characterized by a relatively short treatment duration, yet the women had a notably high rate of later AD and recurrent episodes of postpartum AD. The recurrence risk of postpartum AD was markedly higher among women with PPD hospital contact after first birth compared to women with postpartum antidepressant medication after first birth. Our results underline the necessity of measures targeted at specific vulnerable groups, such as women who experience PPD as a first psychiatric episode.

The objective of the study was to investigate familial aggregation of primary congenital hydrocephalus in an unselected, nationwide population. Based on the Danish Central Person Register, we identified all children born in Denmark between 1978 and 2008 and their family members (up to third-degree relatives). Information on primary congenital hydrocephalus was obtained from the National Patient Discharge Register. Using binomial log-linear regression, we estimated recurrence risk ratios of congenital hydrocephalus. An alternative log-linear regression model was applied to quantify the genetic effect and the maternal effect. Of 1 928 683 live-born children, 2194 had a diagnosis of idiopathic congenital hydrocephalus (1.1/1000). Of those, 75 (3.4%) had at least one other family member with primary congenital hydrocephalus. Significantly increased recurrence risk ratios of primary congenital hydrocephalus were observed for same-sex twins, first- and second-degree relatives as follows: 34.8 (95% confidence interval: 16.4-74.0), 6.2 (95% confidence interval 4.3-8.9) and 2.2 (95% confidence interval 1.6-3.1), respectively. Recurrence risk ratio for third-degree relatives was 1.5 (95% confidence interval 0.8-2.7). A maternal component was supported by the facts that recurrence risk ratios for opposite-sex twins (37.3, 95% confidence interval 11.9-116.7) were significantly higher than other first-degree relatives and that recurrence risk ratios for maternal half-siblings (8.4, 95% confidence interval 3.7-18.7) were significantly higher than for paternal half-siblings (3.0, 95% confidence interval 0.8-12.2). This population-based study found strong evidence of familial aggregation of primary congenital hydrocephalus, which supports the existence of a genetic component to the aetiology. In addition, the pattern of association suggests that a strong maternal component contributes to the familial aggregation.

The higher risk for isolated CHC in first-born children as well as behavioural aspects and comorbidities associated with maternal use of antidepressants, should be the targets for future research. Potential biological pathways by which antidepressants may cause hydrocephalus remain to be elucidated.

(Abstracted from Cell 2020;181:1680–1692) Pregnancy is a vital time period for both mothers and fetuses, and obstetric care can greatly increase positive outcomes of mothers and children. Accurate prediction of gestational age is one of the many important components of care during pregnancy.