From THIN, we identified 512,574 pregnancies among a cohort of 331,414 mothers. More than half of women were aged 25–34 years and 0.4% of their pregnancies ended in perinatal death (stillbirth or neonatal death), 12.6% in miscarriage and 14.7% in termination (). Pregnancies ending in terminations were more likely to be in younger women with a history of smoking and from socio-economically deprived groups whilst miscarriage was more common in older women, compared with pregnancies ending in live births. Pregnancies ending in perinatal death were also more likely to occur in women from deprived groups and in those who were overweight or obese, compared with live-birth pregnancies.
Maternal characteristic for all pregnancy outcomes.
Pregnancies ending in adverse outcomes were more common in all exposure groups compared with the referent group of women with no current or past depression or anxiety (). The prevalence of miscarriage and perinatal death was highest among women prescribed psychotropic drugs, especially those receiving benzodiazepines, the less common medications (Group 6) and those receiving multiple classes of medication. In women prescribed benzodiazepines only, 0.7% of pregnancies ended in perinatal death and 16.2% in miscarriage. The equivalent proportions for women with un-medicated depression or anxiety were 0.6% and 12.1%, and for those in the referent group were 0.4% and 12.1% respectively (). In addition, greater proportions of women terminated their pregnancies if they were exposed to psychotropic medication during early pregnancy.
Breakdown of live and non-live pregnancy outcomes by different antenatal diagnostic and drug exposures.
presents the relative risk ratios for each adverse outcome for each exposure category compared with the referent group. Since the unadjusted and multivariable models produced nearly identical effect estimates, we present adjusted results only. Compared with women from the referent group, women with a history of depression or anxiety and exposure to psychotropic medication during the first trimester of pregnancy had consistently increased risks of all non-live pregnancy outcomes. Effect estimates for exposures to different drugs (especially to SSRIs, benzodiazepines and the less common drug classes, and to multiple classes) were greater than those for un-medicated current illness or for a historical depression or anxiety diagnosis. The greatest effects were found in women prescribed the less common medications (Group 6: adjusted RRRs
3.7, 2.0 and 2.6, 99% CIs 1.9–7.5, 1.7–2.5 and 2.1–3.1 for the risks of perinatal death, miscarriage and termination, respectively) ().
Adjusted relative risk ratios of each adverse pregnancy outcome relative to live birth in each antenatal diagnostic and drug exposure category compared with no current/past depression or anxiety (512,574 pregnancies in 331,414 women).
shows relative risk ratios for all adverse pregnancy outcomes in the whole population of women (512,574 pregnancies in 331,414 women) after adjusting for the number of previous known live births (a proxy of parity). The results were almost identical to the main estimates in . Table S2
shows the results from the same analysis but in the 146,887 pregnancies that occurred in women registered by age 20 (85,260 women, 26% of the total population). Although power was reduced, relative risk ratios were similar to our main results with almost all risk estimates remaining within the 99% confidence intervals of the estimates in . Risk estimates for termination did reduce modestly, yet all adverse outcomes still showed increased treatment-associated risks.
Assessing risks of medication use in women with depression or anxiety only
Compared with pregnancies in women with un-medicated depression or anxiety, women prescribed psychotropic medication had increased risks of all non-live pregnancy outcomes, although most of the results for perinatal death were not statistically significant at the 1% level (). The greatest effects were again found among women in Group 6 (adjusted RRRs
2.7, 2.0 and 2.3, 99% CIs 1.1–6.6, 1.6–2.5 and 1.8–2.8 for the risks of perinatal death, miscarriage and termination, respectively).
Adjusted relative risk ratios of each adverse pregnancy outcome relative to live birth in each antenatal drug exposure category compared with un-medicated antenatal depression or anxiety.
Assessing effects of continued medication use in pregnancy
shows the adjusted RRRs of non-live pregnancy outcomes in pregnant women continuing with each psychotropic medication during the first trimester of pregnancy compared with those who discontinued the medication. There were no increased risks of non-live pregnancy outcomes in women continuing with TCAs during pregnancy compared with those discontinuing them. In contrast, women who continued with SSRIs and benzodiazepines had modest increased risks of miscarriage (RRRs
1.2 and 1.5, 99% CIs 1.0–1.3 and 1.0–2.1, respectively) as well as termination (RRRs
1.5 and 1.9, 99% CIs 1.3–1.6 and 1.4–2.6, respectively) compared with those who did not.
Adjusted relative risk ratios of each adverse pregnancy outcome relative to live birth in pregnancies where women continued psychotropic medication use during the first trimester compared with those where women discontinued use.