Each year at least 600,000 infants born in the United States are exposed to maternal Major Depressive Disorder (MDD) during gestation. Fetal exposure to maternal MDD is associated with newborn medical and neurobehavioral deficits and long term emotional, behavioral, and social problems in the child. Treatment of MDD is critical. Currently, selective serotonin reuptake inhibitors (SSRIs) and dual-action serotonin and norepinephrine reuptake inhibitors (SNRIs) are the first-line pharmacological treatment choice for MDD (collectively SRIs). Recent studies suggest that gestational exposure to SRIs is associated with transient adverse neonatal symptoms consistent with serotonin toxicity or discontinuation syndrome (withdrawal) as seen in adults. Our proposed study will address critically important but unknown issues in this area - if the symptoms are related to serotonin toxicity, exposure to maternal MDD, or if they constitute a true withdrawal syndrome. The proposed study brings together an interdisciplinary team of experienced researchers to address critical questions on the effects of prenatal exposure on infant health and development using a drug exposure model. Our study will use a controlled, drug-exposure methodology that has been successfully applied to other licit and illicit drugs. We plan to study four groups of 70 women each based on their treatment choices by the third trimester: 1) SRI use/no current MDD criteria, 2) MDD/no medication treatment, 3) MDD and SRIs and 4) no current MDD or SRI use. Psychiatric diagnoses will be determined using a standardized clinical interview. We will examine fetal neurobehavior at 28 and 36 weeks gestation using ultrasound observation and fetal heart rate monitoring. Newborns will be examined utilizing serial neurobehavioral assessments and a neonatal drug withdrawal assessment scale on days 0, 1, 2, 4, 7, 14, and 30 with measures of sleep, and physiological and behavioral reactivity. We will adress 3 main specific aims: 1. Determine the effects of gestational SRI exposure on fetal and infant neurobehavior including withdrawal in the neonatal period, 2. Examine the neurobehavioral developmental profile from 26 to 44 weeks gestational age, and 3. Determine if amount of SRI exposure, serotonin metabolite levels, and infant SRI serum drug levels are related to fetal and infant neurobehavior including withdrawal in the neonatal period.The proposed study brings together an experienced multidisciplinary team to address critical questions on the effects of prenatal Serotonin Reuptake Inhibitors (SRI) exposure on infant health and development using a drug exposure model. The model will systematically evaluate the development of neurobehavioral effects attributed to prenatal SRI exposure, distinguishing these effects from those related to maternal major depression exposure. The data from this study will lead to the development of better treatment guidelines for the prenatal use of SRI medications as well as treatment guidelines for infants demonstrating adverse symptoms.
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