Perinatal depression and risk of mortality: nationwide, register based study in Sweden

Abstract

Objective: To determine whether women with perinatal depression are at an increased risk of death compared with women who did not develop the disorder, and compared with full sisters.

Design: Nationwide, register based study.

Setting: Swedish national registers, 1 January 2001 to 31 December 2018.

Participants: 86 551 women with a first ever diagnosis of perinatal depression ascertained through specialised care and use of antidepressants, and 865 510 women who did not have perinatal depression were identified and matched based on age and calendar year at delivery. To address familial confounding factors, comparisons were made between 270 586 full sisters (women with perinatal depression (n=24 473) and full sisters who did not have this disorder (n=246 113)), who gave at least one singleton birth during the study period.

Main outcome measures: Primary outcome was death due to any cause. Secondary outcome was cause specific deaths (ie, unnatural and natural causes). Multivariable Cox regression was used to estimate hazard ratios of mortality comparing women with perinatal depression to unaffected women and sisters, taking into account several confounders. The temporal patterns of perinatal depression and differences between antepartum and postpartum onset of perinatal depression were also studied.

Results: 522 deaths (0.82 per 1000 person years) were reported among women with perinatal depression diagnosed at a median age of 31.0 years (interquartile range 27.0 to 35.0) over up to 18 years of follow-up. Compared with women who did not have perinatal depression, women with perinatal depression were associated with an increased risk of death (adjusted hazard ratio 2.11 (95% confidence interval 1.86 to 2.40)); similar associations were reported among women who had and did not have pre-existing psychiatric disorder. Risk of death seemed to be increased for postpartum than for antepartum depression (hazard ratio 2.71 (95% confidence interval 2.26 to 3.26) v 1.62 (1.34 to 1.94)). A similar association was noted for perinatal depression in the sibling comparison (2.12 (1.16 to 3.88)). The association was most pronounced within the first year after perinatal depression but remained up to 18 years after start of follow up. An increased risk was associated with both unnatural and natural causes of death among women with perinatal depression (4.28 (3.44 to 5.32) v (1.38 (1.16 to 1.64)), with the strongest association noted for suicide (6.34 (4.62 to 8.71)), although suicide was rare (0.23 per 1000 person years).

Conclusions: Even when accounting for familial factors, women with clinically diagnosed perinatal depression were associated with an increased risk of death, particularly during the first year after diagnosis and because of suicide. Women who are affected, their families, and health professionals should be aware of these severe health hazards after perinatal depression.

Fig 1

Hazard ratio (with 95% confidence interval) for all cause mortality among women with perinatal depression, compared with matched women with no perinatal depression. (A) Perinatal depression and (B) Antepartum depression, and (C) postpartum depression. *Time varying hazard ratios and 95% confidence intervals were derived from flexible parametric survival models allowing relative risk of perinatal depression to vary over time. A spline with five degrees of freedom was used for the baseline cumulative hazard, and three degrees of freedom was used for the time-varying effect. Models for perinatal and antepartum depression were adjusted for maternal age, calendar year at delivery, educational level, annual household income, country of birth, cohabitation status, parity, body mass index, smoking during early pregnancy, pre-existing psychiatric disorder, hypertensive and diabetic disorders. Model for postpartum depression was additionally controlled for delivery mode, gestational age, child loss, and birth weight