The use of selective serotonin reuptake inhibitors by women during pregnancy increases the risk of persistent pulmonary hypertension in newborns, with the risk doubling for use during late pregnancy.
The risk of persistent pulmonary hypertension of the newborn (PPHN) after exposure to any SSRI in late pregnancy was more than doubled (adjusted odds ratio, 2.1). The risk was slightly increased in association with exposure to SSRIs in early pregnancy (adjusted OR, 1.4). The combination of a previous admission to hospital for a psychiatric disorder and exposure to an SSRI in late pregnancy yielded an adjusted OR of 3.1. The findings – from a population-based cohort study of data from registries in five Nordic countries – were published Jan. 12 in BMJ (2011;344:d8012 [doi:10.1136/bmj.d8012]).
"As the risk in association with treatment in late pregnancy seems to be more than doubled, we recommend caution when treating pregnant women with SSRIs. It is essential to plan the treatment and to weigh the risks of persistent pulmonary hypertension of the newborn when treating women in late pregnancy with those of relapse of depression and neonatal abstinence syndrome if therapy is interrupted. For women where treatment with an SSRI is the only or best option, the choice of substance seems to be of minor importance," said Dr. Helle Kieler, an ob.gyn. at the Centre for Pharmacoepidemiology at the Karolinska Institute in Stockholm, and her coinvestigators.
The researchers included women and their infants born in Denmark, Finland, Iceland, Norway, or Sweden between 1996 and 2007. Each of these countries has national registers with prospectively collected information on the health of all inhabitants. They obtained data from the medical birth registers, the prescription registers, and the cause of death registers from all five countries. Data on the mother’s previous psychiatric diseases and infant diagnoses were included for Denmark, Iceland, Sweden, and Finland and from the Danish Psychiatric Central Register.
The investigators included all singletons born after 33 weeks’ gestation between 1996 and 2007. Births were included only from the years when prescription data were available. They obtained information on PPHN, level of delivery hospital, maternal smoking, body mass index (BMI) in early pregnancy, year of birth, mode of delivery, gestational age at birth, birth weight, meconium aspiration, and maternal diseases recorded during pregnancy from the national registers.
The researchers also collected information about the mothers’ admissions to hospital for a psychiatric diagnosis during the 10 years before giving birth. In addition, they identified women who had filled prescriptions for antidepressants, antidiabetes drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs) from 3 months before the start of pregnancy until delivery.
Dr. Kieler and her associates included six SSRIs in the analyses: fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), and escitalopram (Lexapro). They also performed subanalyses on whether other antidepressants with an effect on serotonin activity or norepinephrine activity would affect the risks of PPHN. Patient use was as "ever use" (3 months before the start of pregnancy until birth), as a filled prescription in late pregnancy (from 140 days after the start of pregnancy until birth), or in early pregnancy only (from 3 months before the start of pregnancy until a pregnancy length of 55 days).
Potential confounders included maternal smoking, age, BMI, purchased NSAIDs and antidiabetes drugs, diseases recorded during pregnancy, level of delivery hospital (university or nonuniversity hospital), and infants’ country of birth, birth year, and birth order.
In total, 1,618,255 singleton births were included. Of these, 0.7% of the mothers had filled a prescription for an SSRI during late pregnancy and 1.1% in early pregnancy only. The mothers with a filled prescription for an SSRI tended to be older and more often smokers than mothers not using SSRIs. Exposed infants had a lower gestational age at birth and were more often classified as small for gestational age. The absolute risk for PPHN for infants to mothers using SSRIs was as low as 3 infants per 1,000 exposed.
In late pregnancy, 627 women had filled a prescription for an antidepressant with an effect on serotonin activity or norepinephrine activity. The corresponding figure for early pregnancy only was 2,503. More than three-quarters (85%) of 63,615 women with a previous psychiatric diagnosis had not filled a prescription for any of the antidepressants during pregnancy.
"We recommend caution when treating pregnant women with SSRIs."
Among the 11,014 infants exposed to an SSRI in late pregnancy, 33 (0.3%) had a diagnosis of PPHN – three of whom had meconium aspiration. Among 627 infants exposed to antidepressants with an effect on serotonin activity or norepinephrine activity, 3 (0.5%) had a diagnosis of PPHN. Of the 17,053 infants exposed to SSRIs only in early pregnancy, 32 (0.2%) had PPHN; 0.1% of the 1,588,140 infants never exposed to SSRIs were diagnosed with PPHN.