Why the Maternal Medication List Matters: Neonatal Toxicity From Combined Serotonergic Exposures

Brajcich, Michelle; Palau, Mauricio A.; Messer, Ricka; Murphy, Michael E.; Marks, Jill

doi:10.1542/peds.2019-2250

Cited by 7 publications

(3 citation statements)

References 17 publications

(19 reference statements)

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“…Additionally, although persistent pulmonary hypertension of the newborn is the most recognizable complication from in utero SSRI exposure ( 5 , 18 ), we described less commonly reported SSRI-induced homeostatic imbalance—neonatal acidemia, hyperlactemia, and hypocalcemia. Neonatal providers should be aware of possible outcomes to discern between serotonin syndrome, drug withdraw, and other SSRI-related perinatal morbidity ( 45 , 50 ).…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine-induced perinatal morbidity in a sheep model

et al. 2022

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Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants used by pregnant women. However, adverse pregnancy outcomes have been described in women taking SSRI during pregnancy—placental lesions, premature birth, poor neonatal adaptation. We aimed to investigate the effects of fluoxetine (Prozac® most commonly used SSRI) treatment during the last month of gestation on pregnancy complications, placental and neonatal health in a non-depressed sheep model. On day 119 ± 1 postbreeding (experimental day 0; E0) of a 151-day expected gestation, Hampshire ewes were randomly assigned to receive fluoxetine (n = 9 ewes, 15 lambs; daily intravenously treatment with 10 mg/kg on E0 and E1 and 5 mg/kg daily thereafter until parturition) or to a control group (n = 10; 14 lambs; vehicle only). Blood samples from ewes were collected throughout the experimental period and postpartum; blood from lambs were collected postpartum. Analysis of variance was used for statistical analysis. Fluoxetine treatment reduced placentome growth during the last month of pregnancy. Gestation length was decreased by 4.5 days in fluoxetine-treated ewes. Birthweight was reduced in lambs exposed to fluoxetine in utero; weights remained decreased until postnatal day 3. Placentome diameter by birthweight ratio was not different between groups suggesting that the decreased placentome diameter was accompanied by decreased lamb birthweight. During the first week postnatal, lambs exposed to fluoxetine in utero had decreased blood pH and decreased total carbon dioxide, bicarbonate, and base excess and increased lactate (days 3–6), collectively indicative of metabolic acidemia. Additionally, ionized calcium was decreased between postnatal days 0 to 4 in lambs exposed to fluoxetine in utero. Using a non-depressed animal model clearly defines a role for SSRI on the occurrence of perinatal complications and neonatal morbidity. The decreased placentome diameter, shortened gestation, decreased birthweight, decreased calcium levels, and neonatal acidemia suggest the occurrence of intrauterine growth restriction. The persistence of neonatal acidemia for several days postpartum suggests poor neonatal adaptation to extrauterine environment.

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Section: Discussionmentioning

confidence: 99%

Fluoxetine-induced perinatal morbidity in a sheep model

et al. 2022

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“…Noteworthy, persistent pulmonary hypertension of the newborn seems to be Transient decreased fetal blood pH, partial pressure of oxygen and oxygen saturation, increased partial pressure of carbon dioxide, higher maternal and fetal blood pressure [64] related to increased pulmonary vascular resistance associated with increased neonatal circulating serotonin. Additionally, some researchers have claimed that what has been previously described as neonatal withdrawal might be serotonin syndrome due to increased neuronal serotonin concentrations and signaling [121][122][123][124].…”

Section: Pregnancy Outcomes-focus On Iugr and Preterm Birthmentioning

confidence: 99%

Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation

Domingues

Wiltbank

Hernández

2023

Biology of Reproduction

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Maternal use of antidepressants has increased throughout the last decades; selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressants. Despite the widespread use of SSRI by women during reproductive age and pregnant women, an increasing amount of research warns of possible detrimental effects of maternal use of SSRI during pregnancy including low birthweight/small for gestational age and preterm birth. In this review we revisited the impact of maternal use of SSRI during pregnancy, its impact on serotonin homeostasis in the maternal and fetal circulation and in the placenta, and its impact on pregnancy outcomes – particularly intrauterine growth restriction and preterm birth. Maternal use of SSRI increases maternal and fetal serotonin. The increase in maternal circulating serotonin and serotonin signaling likely promotes vasoconstriction of the uterine and placental vascular beds decreasing blood perfusion to the uterus and consequently to the placenta and fetus with potential impact on placental function and fetal development. Several adverse pregnancy outcomes are similar between women, sheep, and rodents (decreased placental size, decreased birthweight, shorter gestation length/preterm birth, neonatal morbidity and mortality) highlighting the importance of animal studies to assess the impacts of SSRI. Herein, we address the complex interactions between maternal SSRI use during gestation, circulating serotonin, and the regulation of blood perfusion to the uterus and fetoplacental unit, fetal growth, and pregnancy complications.

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“…Psychotropic medications that are taken during pregnancy can pose risks of toxic effects to both mother and fetus [1,2]. About 8-12% of pregnant women take antidepressants [2][3][4] and selective serotonin reuptake inhibitors (SSRI) are the most commonly used antidepressant [4,5].…”

Section: Introductionmentioning

confidence: 99%

Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality

Domingues

Fricke

Sheftel

et al. 2022

Toxics

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Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

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Why the Maternal Medication List Matters: Neonatal Toxicity From Combined Serotonergic Exposures

Cited by 7 publications

References 17 publications

Fluoxetine-induced perinatal morbidity in a sheep model

Fluoxetine-induced perinatal morbidity in a sheep model

Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation

Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality

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