Placental Transfer of SSRI and SNRI Antidepressants and Effects on the Neonate

Rampono, Jon; Simmer, Karen; Ilett, K. F.; Hackett, L.P.; Doherty, Dorota; Elliot, Rosemary H.; Kok, Chooi Heen; Coenen, A.M.L.; Forman, Thomas E.

doi:10.1055/s-0028-1103296

Cited by 219 publications

(205 citation statements)

References 25 publications

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“…These findings are biologically plausible given that SSRIs interact with the placenta, 10 may raise maternal serotonin to abnormal levels, and act directly on the fetus. 41 Serotonin' s integral role in fetal brain development includes modulating early neurodevelopmental processes such as cell division, neurite outgrowth, and neuronal migration, 5 with the first trimester a period of development especially sensitive to alterations in serotonergic functioning. Recent reviews give a more detailed discussion relating prenatal SSRI use with ASD and other developmental outcomes.…”

Section: Discussionmentioning

confidence: 99%

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Serotonin is critical in early brain development, creating concerns regarding prenatal exposure to factors influencing serotonin levels, like selective serotonin reuptake inhibitors (SSRIs). Prenatal SSRI use was recently associated with autism; however, its association with other developmental delays is unclear. WHAT THIS STUDY ADDS:This population-based case-control study in young children provides evidence that prenatal SSRI use may be a risk factor for autism and other developmental delays. However, underlying depression and its genetic underpinnings may be a confounder.abstract OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs).METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a populationbased case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information. RESULTS:Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07-7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17-8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98-11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20-20.62). Findings were similar among mothers with an anxiety or mood disorder history. CONCLUSIONS:In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.

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Section: Discussionmentioning

confidence: 99%

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

et al. 2014

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“…58,59 This is summarized in Table 4, which gives the CYP enzyme messenger ribonucleic acid and protein levels in the human fetus, newborn, child, and adult. It is likely that the differences in the fetal-maternal drug ratios 22,52 reflect the degree of CYP expression in the fetus, and the extent of inhibition of these CYPs by the various SSRIs and SNRIs.…”

Section: Fetal Contributions To Ssri Metabolism and Dispositionmentioning

confidence: 99%

“…49 As with other epithelial structures, the extent of placental transfer of a molecule depends, in large part, on its physicochemical properties, with placental permeability inversely related to molecular size, polarity, and charge, and directly to lipophilicity. 50 All SRIs are lipophilic, 51 leading to high placental permeability, and extensive maternal-to-fetal SSRI transfer in humans has been reported, 22,52 although the fetal-maternal concentrations vary substantially, both within a drug and between drugs. Moreover, associations between cord SRI levels and risk for neonatal behavioural disturbances remain inconsistent, 11,12,52 suggesting other factors, such as fetal metabolism, variations in drug potency as an inhibitor of serotonin reuptake, or the presence of psychoactive metabolites, may also be important predictors of neonatal outcomes.…”

Section: Placental Contribution To Fetal Sri Exposurementioning

confidence: 99%

Fetal Serotonin Reuptake Inhibitor Antidepressant Exposure: Maternal and Fetal Factors

2012

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Prenatal serotonin reuptake inhibitor exposure is common and neonatal outcomes vary greatly, often leading to confusion about whether to use or even continue antenatal use of these antidepressants. Importantly, some but not all infants are affected, which raises questions about how maternal drug metabolism contributes to fetal drug exposure. To address this key question, our paper reviews the role of key maternal, fetal, and placental pharmacokinetic, metabolic, and genetic factors that affect the extent of fetal drug exposure. Considering the role of these factors may further our understanding of variables that may assist in optimizing maternal psychopharmacotherapy during pregnancy and neonatal outcomes. W W WL'exposition prénatale à un inhibiteur du recaptage de la sérotonine est fréquente et les impacts néonataux varient grandement, ce qui provoque souvent la confusion lorsqu'il s'agit d'utiliser ou même de continuer l'usage prénatal de ces antidépresseurs. D'abord et avant tout, certains bébés, mais pas tous, sont affectés, ce qui soulève des questions sur la façon dont le métabolisme maternel des médicaments contribue à l'exposition foetale aux médicaments. Pour aborder cette importante question, notre article examine le rôle des principaux facteurs maternels, foetaux, pharmacocinétiques placentaires, métaboliques, et génétiques qui affectent la portée de l'exposition foetale aux médicaments. Examiner le rôle de ces facteurs approfondira notre compréhension des variables qui peuvent aider à optimiser la psychopharmacothérapie maternelle durant la grossesse et les résultats néonataux.consider the impact of physiological factors of the pregnancy itself and SRI-related pharmacological factors that influence maternal drug metabolism and, by extension, fetal exposure. Further, neonatal outcomes following in utero SRI exposure depends largely on the extent of fetal drug exposure, and thus understanding factors that affect fetal drug pharmacology also offers important clues to developmental risks associated with prenatal drug exposure. Our paper will review key maternal, placental, and fetal metabolic and genetic factors that influence SRI pharmacology and fetal drug exposure. Both SSRIs (for example, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) and SNRIs (for example, duloxetine and venlafaxine) are increasingly used to manage antenatal mood disturbances 8 and will be referred to as SRIs (meaning, SRI ADs). This review is offered as a way to further our understanding of variables that may account for the variations in maternal perinatal SRI pharmacology and neonatal outcomes, and thereby contribute to assessing the benefits and risks associated with SRI use in this setting. E ach year in North America, 15% to 20% of women experience mood disorders (for example, depression) during their pregnancy, leading to one-third of these women being treated with an SRI AD; however, up to 50% stop medication within the first 60 days of pregnancy.

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“…Before 5HT becomes a neurotransmitter in the mature brain, it plays a role as a neurodevelopmental signal, regulating cells and influencing serotonin receptor growth (5). Given that SRIs readily cross the placenta (6) and presumably alter central 5HT levels during critical periods of development, in utero exposure to SRIs may influence behavioral outcomes during childhood.…”

mentioning

confidence: 99%

Prenatal exposure to serotonin reuptake inhibitor antidepressants and childhood behavior

2015

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Background: Animal research has suggested that prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure causes increased anxiety-like behaviors in adulthood. We examined whether in utero SRI exposure influenced externalizing and internalizing behaviors in children at 3 y and again at 6 y of age. Methods: We recruited women in their second trimester of pregnancy from primary maternity care providers in Vancouver British Columbia, Canada. We compared the internalizing, externalizing, and the anxious and attention subscales of the internalizing behaviors scores of children exposed to SRIs and children not exposed to SRIs at age 3 and age 6. results: We included 110 mother-child pairs (44 exposed to SRI and 66 not exposed). Higher levels of internalizing and anxious behaviors were reported in SRI exposed children at both 3 and 6 y of age compared with children who were not exposed (F = 7.52, P = 0.0072 and F = 7.91, P = 0.0058, respectively). The fully adjusted hierarchical regression models indicated a positive and significant relationship between SRI exposure and increased internalizing and anxious behaviors even when controlling for maternal mood during pregnancy, postpartum and childhood. conclusion: SRI exposure was associated with sustained higher levels of internalizing behaviors in early childhood even when controlling for maternal depression.

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Placental Transfer of SSRI and SNRI Antidepressants and Effects on the Neonate

Abstract: Transfer of SSRIs and SNRIs across the placenta was substantial. Neonates developed mild behavioral symptoms in the early perinatal period but these were self-limiting and similar for both SSRIs and the SNRI venlafaxine.

Cited by 219 publications

References 25 publications

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

Fetal Serotonin Reuptake Inhibitor Antidepressant Exposure: Maternal and Fetal Factors

Prenatal exposure to serotonin reuptake inhibitor antidepressants and childhood behavior

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