Between 15 and 20% of pregnant women suffer from depression or anxiety during the perinatal period [1], ∗[2]. Although some women decline pharmacotherapy because of concerns about possible risks of teratogenicity, about 5–13% of pregnant women choose to treat their mood disorder with a serotonin reuptake inhibitor (SRI) antidepressant [1], [3]. Both the disease and its treatment pose risks for mothers and their neonates. Pharmacotherapy poses difficult decisions for the clinician and mother alike, and the evidence supporting a course that promotes both maternal and infant health is often conflicting. Not treating maternal depression is never an option. What are the best options to promoting optimal care for the development and behaviour of infants in mothers who are depressed during pregnancy?
Making sense of studies reporting on the effect of prenatal SRI exposure is challenged by conflicting and contradictory findings, some raising concern [4], [5], whereas others offer reassurance [6], [7], [8]. This might, in part, reflect the inherent challenge in distinguishing between the effects of the SRI exposure from the effects of the underlying indication for the drug treatment, the maternal mood disturbance, and related confounding influences. Compounding this is that a failure to treat maternal depression, anxiety, or both, effectively can lead to compromised prenatal care, increased risk of obstetrical complications, self-medication, substance abuse, or both, which further affects neonatal health [9], [10], [11]. Thus, in examining the evidence, as imperfect as it is, it becomes critical to weigh the risks and benefits of exposing the fetus to maternal mental illness against the risks and benefits of exposure to psychotropic medicines. In this chapter, we aim to present a synthesis of the research evidence on the effects of maternal mood disorders (depression, anxiety, or both) and the use of SRI medicines on neonatal health as a way to guide clinical care of exposed neonates. Three key outcomes (postnatal adaptation syndrome, congenital malformations and persistent pulmonary hypertension) will be used as examples to guide clinical care of the exposed neonate.
Two classes of medications are often combined and referred to as SRIs: selective serotonin reuptake inihibitors that include fluoxetine, paroxetine, sertraline, citalopram, escitalopram, and fluvoxamine; and the selective-norepinephrine reuptake inhibitors, which include venlafaxine, desvenlafaxine, duloxetine, and milnacipran. For the sake of simplicity, no distinction will be made between exposures to either class in this chapter. These medications primarily act by blocking the serotonin transporter (5-HTT), which increases extracellular serotonin levels. Because SRIs readily cross the placenta and the blood–brain barrier [12], maternal prenatal SRI treatment alters central fetal serotonin (5-HT) levels. Serotonin is a widely distributed central neurotransmitter [13], and, given its key role as a developmental signal during early developmental periods [14], it is not surprising that concerns have been raised about the neurobehavioural consequences of altering early 5HT signalling during developmentally sensitive periods ∗[13], ∗[15].
Research on the possible adverse outcomes of SRI exposure in utero, however, has reported contradictory findings, with many studies reporting no increased risk from exposure to SRIs in utero on infant outcomes [16], [17]. This confusion can be explained at least partially, by the key challenge of distinguishing between the effects of the SRI exposure and the effects of the underlying indication for the drug treatment, the maternal mood disturbance. Failure to treat maternal depression, anxiety, or both, effectively can lead to compromised prenatal care, increased risk of obstetrical complications, self-medication, substance abuse, or both, not to mention exposure to the detrimental effects of the illness itself. For the most part, the body of evidence that allows us to make clinical sense of these complex and contradictory research findings remains limited. Our challenge remains one of weighing the risks and benefits of exposing the fetus to maternal mental illness against the risks and benefits of exposure to psychotropic medicines. In this chapter, we aim to present a synthesis of the research evidence on the neonatal effects of prenatal maternal mood disorders and SRI exposure. Three key widely reported neonatal outcomes (postnatal adaptation syndrome, congenital malformations and persistent pulmonary hypertension) that are detectable immediately after delivery are used in this chapter to highlight how evidence might be used to guide a clinical approach to care of the newborn of depressed mothers treated with an SRI during pregnancy.