On 1 March 2011 (1), we published information about two cases of neonatal death in infants whose mothers had been treated with fluoxetine during pregnancy. Since then, we have performed an extended search for adverse drug reaction (side effect) data for all antidepressants of the SSRI type and also for all cases of abortions. Data show a further two cases of neonatal death as well as 12 reports of intra-uterine death (foetal death) or abortions.
Even though the risk is small, serious adverse reactions may occur in the foetus and the newborn child if pregnant women are treated with an antidepressant of the SSRI type. The risk should, however, be weighed against the beneficial effect of SSRIs for pregnant women who suffer from a serious disorder requiring treatment.
Data on suspected serious adverse reactions in newborns
Since 28 February 2011, the Danish Medicines Agency has performed an extended search and manual review of all reported suspected adverse reactions in mothers and child if the mother had taken an SSRI.
As at 7 March 2011, the Danish Medicines Agency’s database of adverse reactions had received 51 reports describing suspected serious adverse reactions in newborns caused by the mother’s use of an antidepressant of the SSRI type during pregnancy. 22 of these reports describe congenital diseases or malformations, four describe deaths.
The individual reports can describe several suspected adverse reactions.
The reported adverse reactions appear from the table in the right-hand factbox (in Danish only). The reporting of a suspected adverse reaction does not necessarily mean that there is a causal relationship (connection) between the medicine and the reported adverse effect.
Four reports on deaths in newborns
Two of the reported neonatal deaths were seen for mothers who had used fluoxetine during pregnancy. These two cases are described in our announcement of 1 March 2011 (1) (see link in the factbox to the right).
After a thorough review of adverse drug reaction data, we have identified a further two cases of deaths in newborns to mothers who had been treated with paroxetine and citalopram, respectively. The information contained in these two adverse drug reaction reports is very limited. The one report describes congenital anomaly, which had caused the child to die, and the other describes congenital heart disease and neonatal death.
12 reports of intra-uterine death (foetal death) or abortion
In addition, 12 reports of foetal death or abortion have been recorded. In three of these cases, the abortion was induced due to foetal malformation.
Nine of the reported cases of spontaneous abortions/foetal deaths contained no indication that foetal malformation had been observed.
The Danish Medicines Agency comments on treatment with SSRI during pregnancy
Pregnant women’s use of fluoxetine and other SSRIs may be associated with a risk of serious adverse reactions in the foetus and the newborn child. There is a risk of cardiac malformation, high blood pressure in the lungs (persistent pulmonary hypertension) or withdrawal symptoms in the child. All three conditions may be life-threatening for the newborn and could thus cause death.
The risk of serious adverse reactions is, however, small and should be weighed against the beneficial effect in pregnant women who suffer from a serious disorder requiring treatment.
Epidemiological studies have shown an increased risk of malformation in the cardiovascular system in newborns to mothers who had taken fluoxetine or paroxetine in the beginning of pregnancy. The studies indicate that approx. 2 in every 100 newborns have such malformations. In comparison, the occurrence of malformation in the cardiovascular system among all children is approx. 1 in every 100.
Epidemiological studies indicate that women’s use of SSRIs during pregnancy, particularly in late pregnancy, may increase newborns’ risk of high blood pressure in the lungs (persistent pulmonary hypertension). The observed risk is approx. 5 cases in every 1000 pregnancies. In comparison, the occurrence of this disorder among all children is approx. 1-2 in every 1000 births.
Use of SSRIs during pregnancy may cause withdrawal symptoms in the newborn. In most cases, the withdrawal symptoms are not serious, e.g. irritability, crying, difficulty in sucking or in sleeping. In some cases, serious adverse reactions could occur such as seizures or breathing difficulties.
The active substances contained in SSRIs are excreted in breast milk, and there have been reports of adverse reactions in breastfed children.
Additional information
For more information on treatment with antidepressants during pregnancy, please see the factbox to the right.
(1) This information was published in Danish on 28 February 2011
