Antidepressants are dispensed to a large number of pregnant women and we have previously published data on the dispensing patterns and the characteristics of the WA women dispensed an SSRI during their pregnancy.[13
] It is important to have follow-up information on the developmental well-being of the children exposed to SSRIs in utero
. This is the first population-based study in Australia to examine the early hospital admissions of the children born to women dispensed an SSRI during their pregnancy. In this cohort, an SSRI was dispensed to 3703 (3.8%) pregnant women with 3764 children in utero
. It is also one of the largest studies of pregnant women using SSRIs to follow the children through to 2 years of age to investigate morbidity and mortality.
Our study shows that children born to women dispensed an SSRI during their pregnancy were still more likely to be born preterm than children born to women not dispensed an SSRI during pregnancy after adjusting for any previous preterm births, whether the mother smoked during her pregnancy, SEIFA, parity and maternal age. Their mean birth weight was 100 g less than the mean weight of children in the non-SSRI group. Following the birth admission and before the age of 2 years, the children in the SSRI group were more likely to be admitted for bronchiolitis, which remained a significant risk for admission after stratifying by whether the mother smoked during her pregnancy. The mothers who smoked during their pregnancy probably continued to smoke around their child in the home. However, the mothers who didn’t smoke during their pregnancy had a higher risk of their child being admitted for bronchiolitis than the mothers who did smoke (OR 1.7; 95% CI 1.4, 2.0 vs OR 1.1; 95% CI 0.8, 1.5) when compared with the non-SSRI mothers. The next more likely admission was for ‘persons encountering health services in other circumstances’ – a category usually assigned when a healthy child is admitted due to family circumstances. These admissions may be related to the underlying depressive condition of the mother and her ability to cope with a newborn.
The main limitation of using dispensing data relates to whether the medicine was consumed, or consumed as directed, and we have no information in this study for either of these aspects of use. It is not known whether the mother actually ingested the medicine but by reviewing the repeat dispensing of SSRIs throughout the trimesters of pregnancy, adherence to the medicines may be inferred. 75.4% of the women were dispensed an SSRI in at least two consecutive trimesters, from T0 to T3,[13
] and this would indicate the women are using the SSRIs as each dispensing costs from $A3.60 to $A4.60 per medicine for concessional patients and from $A22.40 to $A28.60 for general patients, during the period of the study. The mean number of dispenses was 2.2 in T1 and 4.4 overall. If the depression per se
is the reason for the increased risks and women with depression are not treated with SSRIs or treated with non-SSRI medicines, the effects observed in our study would be understated as those women would be in the non-SSRI group. Whilst the study is based upon births in WA from 2002 to 2005, the SSRI medications analysed are still the most commonly prescribed SSRIs given to pregnant women. Although the use of administrative data may not provide a complete picture of the factors associated with the use of medications in pregnancy, the approach provides a rich source of information on pregnancy outcomes in large populations.
A review of perinatal depression concluded that, although limited, the available research suggests that depression is one of the most common perinatal complications.[27
] Since 2006, the American College of Obstetricians and Gynecologists has recommended screening for depression during each trimester of pregnancy.[28
] The first Australian Clinical Practice Guidelines surrounding the detection, management and treatment of perinatal mental health disorders were established in 2011.[29
] Australian studies have also highlighted the need for screening pregnant women.[30
] The risks of allowing a depressive episode to remain untreated may be far greater than those associated with antidepressant treatment.[3
] Depression may increase the risk of self-injurious or suicidal behaviours in the mother but also may contribute to inadequate self-care and poor compliance with prenatal care.[32
] Women with depression often present with decreased appetite and consequently lower-than-expected weight gain in pregnancy, factors that have been associated with negative pregnancy outcomes.[32
] In addition, persons with a major depressive disorder are twice as likely to smoke as other persons[34
] and to use either alcohol or illicit drugs,[33
] behaviours that further increase risk to the foetus.[37
] Although it has been difficult to assess the impact of antenatal depression on foetal development and neonatal well-being in humans, several studies have found an association between maternal depression and factors that predict poor neonatal outcome, including preterm birth, lower birth weight, smaller head circumference and lower APGAR scores.[37
] A recent study by Ponder et al.[44
] found that maternal depression/anxiety affected a particular gene expression in the placenta suggesting a possible mechanism for the effects of maternal mood on foetal neurodevelopmental programming. Studies have shown that SSRIs readily cross the placenta,[6
] are present in amniotic fluid[7
] and newborns exposed to them in utero
may experience withdrawal-like symptoms after birth.[8
The FDA have issued a Drug Safety Communication (14 December 2011) related to the use of SSRIs during pregnancy and the potential risk of a rare heart and lung condition known as persistent pulmonary hypertension of the newborn (PPHN).[45
] The initial Public Health Advisory in July 2006 on this potential risk was based on a single published study.[46
] Since then, there have been conflicting findings from new studies evaluating this potential risk, making it unclear whether use of SSRIs during pregnancy can cause PPHN. Two studies suggest an increased risk for PPHN with SSRI use in pregnancy[46
] and three studies reported no increase in risk of PPHN.[48
] The FDA has reviewed the additional new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN. It was noted by the FDA communication that PPHN typically presents in term or late-preterm births, and that Caesarean delivery was a potentially important factor. These admissions would most likely have been coded in our data as ‘P29.3 persistent fetal circulation, delayed closure of ductus arteriosus, pulmonary hypertension of newborn (persistent)’. In term births, our study had 8 children in the SSRI group and 86 in the non-SSRI group with this as the principal diagnosis or as an additional diagnosis recorded on their birth admission (OR 2.4; 95% CI 1.2, 5.0). After adjusting for Caesarean delivery, the risk did not change. A very large population-based study in five Nordic countries of births from 1996 to 2007 has been published since the FDA communication. They reported 33 children in the SSRI group with PPHN with an unadjusted OR of 2.5; 95% CI 1.8, 3.6.[51
] The absolute risk of PPHN is still low, and the P29.3 code also includes patent ductus arteriosus.