Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn

Department of Pediatrics, University of California, San Diego, La Jolla, CA 92103, USA.
New England Journal of Medicine (Impact Factor: 55.87). 03/2006; 354(6):579-87. DOI: 10.1056/NEJMoa052744
Source: PubMed


Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant mortality and morbidity. A previous cohort study suggested a possible association between maternal use of the selective serotonin-reuptake inhibitor (SSRI) fluoxetine late in the third trimester of pregnancy and the risk of PPHN in the infant. We performed a case-control study to assess whether PPHN is associated with exposure to SSRIs during late pregnancy.
Between 1998 and 2003, we enrolled 377 women whose infants had PPHN and 836 matched control women and their infants. Maternal interviews were conducted by nurses, who were blinded to the study hypothesis, regarding medication use in pregnancy and potential confounders, including demographic variables and health history.
Fourteen infants with PPHN had been exposed to an SSRI after the completion of the 20th week of gestation, as compared with six control infants (adjusted odds ratio, 6.1; 95 percent confidence interval, 2.2 to 16.8). In contrast, neither the use of SSRIs before the 20th week of gestation nor the use of non-SSRI antidepressant drugs at any time during pregnancy was associated with an increased risk of PPHN.
These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy.

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Available from: Christina D Chambers, Jul 21, 2015
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    • "However, maternal SSRI use may be problematic as SSRIs such as fluoxetine (Prozac) can cross the placental barrier (Hendrick et al., 2003) and pass into breast milk (Wisner et al., 1996; Weissman et al., 2004), potentially affecting the developing offspring. Indeed, perinatal SSRI exposure is associated with adverse outcomes in the infant such as reduced weight gain (Chambers et al., 1999), levels of reelin required for normal brain development (Brummelte et al., 2013), psychomotor scores during the first year (Santucci et al., 2014), increased hypertension (Chambers et al., 2006), cardiac defects (Malm et al., 2011), and risk for autism (Croen et al., 2011). However, the negative effects of perinatal fluoxetine may outweigh the detrimental effects of untreated maternal depression on child development . "
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    ABSTRACT: Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and represents a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of postpartum depression. Antidepressants, such as fluoxetine, are commonly prescribed for treating postpartum depression. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations.
    Neuropharmacology 09/2015; DOI:10.1016/j.neuropharm.2015.09.001 · 5.11 Impact Factor
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    • "studies indicated that prenatal exposure to SSRIs increased the risk for low birth weight and preterm birth (Chambers, Johnson, Dick, Felix, & Jones, 1996), and for persistent pulmonary hypertension (Chambers et al., 2006). Prenatal SSRI exposure was also associated with a self-limiting neonatal withdrawal syndrome, including tremor, restlessness and rigidity (Laine, Heikkinen, Ekblad, & Kero, 2003; Moses-Kolko et al., 2005; Olivier et al., 2011). "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRI) are commonly prescribed antidepressant drugs in pregnant women. SSRIs cross the placental barrier and affect serotonergic neurotransmission in the fetus. Although no gross SSRI-related teratogenic effects were reported, infants born following prenatal exposure to SSRIs are at higher risk for various developmental abnormalities. The aim of this study was to examine the effects of prenatal SSRI on social and maternal behavior in mice. To this end, pregnant female dams were exposed to saline or fluoxetine (FLX) throughout pregnancy, and the behavior of the offspring was examined. The results indicate that in utero FLX increased aggression in adult males and delayed emergence of maternal behavior in adult females. Social exploration and recognition memory were not affected by prenatal FLX exposure. These findings support the notion that alterations in the development of serotonergic pathways following prenatal exposure to SSRIs are associated with changes in social and maternal behavior throughout life. © 2015 Wiley Periodicals, Inc. © Dev Psychobiol. © 2015 Wiley Periodicals, Inc.
    Developmental Psychobiology 09/2015; DOI:10.1002/dev.21356 · 3.31 Impact Factor
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    • "It is reassuring that once overcome, with the exception of findings from Klinger et al. (2011) reported below, these symptoms have not been observed to have an impact on the child's development. To give another example, currently, there is consensus, backed by a review paper coauthored by one of Dr Robinson's coauthors (Jong et al., 2012), that there is a significant, if small, increase in the risk of persistent pulmonary hypertension of the newborn (PPHN) originally described by Chambers et al. (2006) after third trimester SSRI exposure. Dr Robinson's wording, " clinically the absolute risk of PPHN is very "
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    ABSTRACT: The paper by Robinson posits that risks from prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants are not different from the risks encountered in the general population and that untoward effects of SSRIs are difficult to distinguish from those of the mood disorder. Indeed, maternal depression and anxiety can have negative consequences for fetal and postnatal development. Fortunately, experimental evidence suggests that mood and anxiety disorder symptoms often respond to psychosocial interventions. If pharmacotherapy becomes necessary, it is, however, important to know that even if SSRI drugs have been shown to be safe overall, research has shown that fetal development can be adversely affected by in utero exposure to SSRIs in a subgroup of neonates. Examples would be the transient neonatal adaptation syndrome, an increased risk of persistent pulmonary hypertension of the newborn, and small, albeit measurable, changes in motor and social adaptability in infancy and childhood.
    Journal of Nervous & Mental Disease 03/2015; 203(3):167-9. DOI:10.1097/NMD.0000000000000258 · 1.69 Impact Factor
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