EFFECTS OF MULTIPLE NEUROPSYCHIATRIC MEDICATIONS DURING PREGNANCY ON NEONATAL ABSTINENCE SYNDROME (SECOND REPORT)
Authors: Nakagawa *Miyako , Doki Kosuke , Obata-Yasuoka Mana , Hamada Hiromi , Hitaka Daisuke , Miyazono Yayoi , Takada Hidetoshi , Homma Masato 
Published: February 2025

Abstract

Background
Neonatal abstinence syndrome (NAS) is characterized by withdrawal symptoms in neonates because of the discontinuation of transplacental drug transfer after delivery. Although the use of neuropsychiatric drugs in pregnant women is associated with the onset of NAS (Kanemura, 2020), it remains unclear which types of and how many neuropsychiatric drugs are the risk for NAS.

Aims & Objectives
The aim of this study is to investigate the type and number of neuropsychiatric drugs in pregnant women in association with onset of NAS.

Method
Three hundred sixteen mothers who were receiving neuropsychiatric drugs (antipsychotics, antidepressants, antiepileptics, anxiolytics/sedatives) during the pregnancy and their 320 neonates were investigated in University of Tsukuba Hospital during January 2016 to December 2022. NAS was assessed by Isobe score using the checklist for 15 withdrawal symptoms (Kanemura, 2020). Multivariate logistic regression analysis was used to evaluate the relationship between maternal and neonatal background factors, and withdrawal symptoms. This study was approved by the Ethics Committee of the University of Tsukuba Hospital.

Results
The mothers were receiving one (n=169, 53%), two (n=86, 27%), and three or more neuropsychiatric drugs (n=65, 20%) (a maximum, seven drugs). One hundred sixty-three neonates developed withdrawal symptoms 1-10 days after delivery. The incidence of withdrawal symptoms depended on the number of neuropsychiatric drugs during the pregnancy. Significant difference was observed in the incidence of withdrawal symptoms between one or two drugs (45%) and three or more drugs (74%) (P&lt;0.001). The mean Isobe scores also increased with the number of neuropsychiatric drugs: 1.0 in one drug, 1.4 in two drugs, 2.5 in three drugs, and 2.6 in four or more drugs. Multivariate logistic regression analysis revealed that the onset of withdrawal symptoms was associated with the use of three or more neuropsychiatric drugs during the pregnancy (adjusted odds ratio [95% confidence interval]: 2.40 [1.08-5.32], P=0.03) and primiparity (1.74 [1.08-2.80], P=0.02). In contrast, the type of neuropsychiatric drugs was not a significant risk factor for the onset of withdrawal symptoms: 1.64 [0.96-2.80] for antipsychotics, 1.59 [0.95-2.67] for antidepressants, and 0.93 [0.53-1.65] for anxiolytics/sedatives.

Discussion & Conclusion
The onset of neonatal withdrawal symptoms was associated with the use of three or more neuropsychiatric drugs, regardless the type of pharmacological effects, during the pregnancy. It is considered that concurrent use of multiple neuropsychiatric medications in pregnant women is a risk factor for NAS.

References
[1]Kanemura, A et al. (2020). Evaluation of neonatal withdrawal syndrome in neonates delivered by women taking psychotropic or anticonvulsant drugs: A retrospective chart review of the effects of multiple medications and breastfeeding. European Journal of obstetrics, gynecology, and reproductive biology, 254, 226–230.