PurposeTo estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy.MethodsFrom the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression.ResultsOf the 1,005,319 pregnancies (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and 205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10–1.18) for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80–1.24). No individual selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population.ConclusionWe identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual SSRI in particular were not associated with spontaneous abortions. Further studies are warranted on the newer non-SSRI antidepressants, as we had insufficient data to adjust for important confounding factors.

SUMMARYObjective: We studied the potential impact of antiepileptic drugs (AEDs) on fetal growth and gestational age at birth. Methods: In the Danish Medical Birth Registry, we identified all pregnancies with birth outcomes from 1997 to 2008 and linked with data from the Danish National Prescription Register. We used binomial regression to study preterm birth (<37 weeks), low birth weight (<2,500 g), and small for gestational age (SGA), adjusted for potential confounding factors including maternal age, smoking, substance abuse, cohabitation, income, education, and parity. Results: We identified 679,762 singletons, and 2,928 (0.4%) of these had been exposed to AEDs. Exposure to AEDs was associated with a risk of preterm birth (adjusted risk ratio (aRR) 1.32; 95% confidence interval [CI] 1.16-1.50) when compared to unexposed children. However, when stratifying on maternal epilepsy, there was no association between AED exposure and preterm birth in offspring of women with epilepsy (aRR 1.00; 95% CI 0.82-1.21), whereas there was a risk associated with AED exposure in offspring of women without epilepsy (aRR 1.56; 95% CI 1.27-1.92). AED exposure was associated with a risk of being born with low birth weight (aRR 1.40; 95% CI 1.22-1.60) both for children born of women with epilepsy (aRR 1.32; 95% CI 1.06-1.63) and children born of women without epilepsy (aRR 1.61; 95% CI 1.28-2.02). The risk of being born SGA associated with AED exposure (aRR 1.21; 95% CI 1.10-1.34) was found both in offspring of women with epilepsy (aRR 1.19; 95% CI 1.02-1.37) and without epilepsy (aRR 1.21; 95% CI 1.01-1.45). Significance: Prenatal AED exposure was associated with low birth weight and risk of being born SGA, but only with preterm birth among women without epilepsy.

The loss of a close relative is a common event, yet it is associated with increased risk of serious mental health conditions. No large-scale study has explored up to now the importance of the bereaved person's relation to the deceased while accounting for gender and age. We performed a nationwide Danish cohort study using register information from 1995 through 2013 on four sub-cohorts including all persons aged 18 years exposed to the loss of a child, spouse, sibling or parent. We identified 1,445,378 bereaved persons, and each was matched by gender, age and family composition to five non-bereaved persons. Cumulative incidence proportions were calculated to estimate absolute differences in suicide, deliberate self-harm and psychiatric illness. Cox proportional hazard regression was used to calculate hazard ratios while adjusting for potential confounders. Results revealed that the risk of suicide, deliberate self-harm and psychiatric illness was increased in the bereaved cohorts for at least 10 years after the loss, particularly during the first year. During that year, the risk difference was 18.9 events in 1,000 persons after loss of a child (95% CI: 17.6-20.1) and 16.0 events in 1,000 persons after loss of the spouse (95% CI: 15.4-16.6). Hazard ratios were generally highest after loss of a child, in younger persons, and after sudden loss by suicide, homicide or accident. One in three persons with a previous psychiatric diagnosis experienced suicide, deliberate self-harm or psychiatric illness within the first year of bereavement. In conclusion, this study shows that the risk of suicide, deliberate self-harm and psychiatric illness is high after the loss of a close relative, especially in susceptible subgroups. This suggests the need for early identification of high-risk persons displaying adjustment problems after loss of a close family member, in order to reduce the risk of serious mental health outcomes.Key words: Bereavement, suicide, deliberate self-harm, psychiatric hospitalization, loss of a child, sudden loss (World Psychiatry 2017;16:193-199) Death of a close relative is a common experience in adulthood. In the US, it has been estimated that more than 40,000 parents lose a child every year 1 , and more than half of the population over 65 years are widowed 2 . Although bereavement is a natural life event, it is often followed by emotional suffering and adjustment challenges. Studies have shown an association between the loss of a loved one and a range of mental health complications, particularly depression and post-traumatic stress disorder 3-9

ObjectiveTo determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD).Materials and methodsThis was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.ResultsWe identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20). The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11–3.82) but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48–2.05).ConclusionMPH/ATX was associated with a higher risk of SA, but our study indicated that it may at least partly be explained by confounding by indication. Treatment with MPH/ATX was however associated with low Apgar scores <10, an association not found among women with ADHD who did not use MPH/ATX.

Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth.Design Population based cohort study.Setting Register based study in Denmark, 1997Denmark, -2008 Participants 983 305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1