Date of Award

2017

Document Type

Open Access Dissertation

Department

College of Pharmacy

Sub-Department

Pharmaceutical Sciences

First Advisor

Richard Schulz

Abstract

BACKGROUND: There has been an increase in the diagnosis of depression and the use of antidepressants, especially in women of childbearing age, in the past decade. This has drawn attention to the potential impact of depression and antidepressants on pregnancy and fetal development.

OBJECTIVE: (i) To determine the impact of prenatal exposure to antidepressant on the risk of adverse birth outcomes. (ii) To assess the effect of type of antidepressants on the risk of adverse birth outcomes using selective serotonin reuptake inhibitors as the referent group. (iii) To assess the effect of duration and time of prenatal exposure to antidepressants on the risk of adverse birth outcomes.

METHODS: The study was conducted using a population-based cohort including all singletons deliveries in years 2008 to 2014 in SC Medicaid population. Information on antidepressant medication and diagnosis of depression and birth outcomes were obtained from South Carolina Medicaid database and birth certificates. The exposed group comprised children of mothers who had a diagnosis of depression and used antidepressants at any time during their pregnancy. The reference group comprised children of mothers who had a diagnosis of depression but did not use any antidepressants during pregnancy. We estimated the association using Logistic Regression and Marginal Structural Models.

RESULTS: Approximately 107, 683 women had a diagnosis of depression in the SC Medicaid population. After applying the study inclusion and exclusion criteria, we got the study sample of 4,450 women. And approximately 36% women received antidepressants during pregnancy. (i) In our study we found that using logistic regression the odds of having preterm delivery were 1.58 (95%CI: 1.19 – 2.10) in those who received an antidepressant during pregnancy as compared to those who did not receive any antidepressants at any time during the pregnancy. Using marginal structural models, the odds of preterm delivery were 1.72 times (95% CI: 1.63 – 1.79) in the group that received antidepressants during pregnancy as compared to those who did not. Using logistic regression it was estimated that antidepressant use during pregnancy was associated with higher odds of the infant having low birth weight/being small for gestational age, OR = 1.57 (95% CI: 1.42 – 2.76) and/or NICU admissions, OR: 1.45 (95%CI 1.28 – 2.26). Marginal structural models showed that the prenatal exposure to antidepressants increased the odd of having low birth weight/small for gestational age 1.63 times (95%CI: 1.53 – 1.73) and the odds of having a NICU admission by 1.66 times (95% CI: 1.58 – 1.73). (ii) Upon comparing the different classes of antidepressants to SSRIs we found that the risk of adverse birth outcomes was not significantly different between the different types of antidepressants. Only TCAs had a statistically lower risk of NICU admissions as compared to SSRIs. Using marginal structural models we found that the risk of NICU admissions was 0.85 times (95% CI: 0.65 – 0.97) lower in TCAs as compared to SSRIs. (iii) Exposure to antidepressants in all three trimesters was associated with the risk of adverse birth outcomes. Although the duration of exposure that is the number of days for which the antidepressant was prescribed in each trimester was not associated with the risk of adverse birth outcomes. Conducting additional analysis we found that the risk of low birth weight/small for gestational age and NICU admissions was higher with exposure in the third and second trimester as compared to the first trimester.

CONCLUSION: In conclusion we found that prenatal exposure to antidepressants is significantly associated with a higher risk of adverse birth outcomes such as preterm delivery, low birth weight/small for gestational age, and NICU admissions, irrespective of the type of antidepressant prescribed and duration and trimester of exposure.

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