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Risks of prematurity and low birth weight associated with trimester-specific prenatal benzodiazepine exposure
Vincent Chin-Hung Chen1, Yi-Lung Chen1, Kai-Liang Kao1
1From the Department of Psychiatry, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan (V.C.-H. Chen); Department of Psychiatry, Chang Gung University, Taoyuan, Taiwan (V.C.-H. Chen); Department of Healthcare Administration, Asia University, Taichung, Taiwan (Y.-L. Chen); Department of Psychology, Asia University, Taichung, Taiwan (Y.-L. Chen); Department of Pediatrics, Far Eastern Memorial Hospital (Kao); School of Occupational Therapy, College of Medicine, National Taiwan University (Lee); Department of Psychiatry, Wan-Fang Hospital and School of Medicine, College of Medicine, Taipei Medical University (Lu); Department of Medicine, Mackay Medical College (Wu); Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan (Wu); Institute of Psychiatry, Psychology and Neuroscience, King's College London (Stewart); South London and Maudsley NHS Foundation Trust, London, UK (Stewart).
Insights
Benzodiazepine use in the third trimester of pregnancy significantly increased risks for preterm birth (PTB) and small for gestational age (SGA) infants. Exposure in earlier trimesters showed no significant association with these adverse birth outcomes.
Area of Science:
- Perinatal medicine
- Pharmacology
- Reproductive health
Background:
- Benzodiazepine exposure during pregnancy may cause fetal abnormalities.
- The impact of benzodiazepine use across different trimesters on birth outcomes requires investigation.
Purpose of the Study:
- To assess the association between benzodiazepine exposure during pregnancy and the risks of preterm birth (PTB) and small for gestational age (SGA) infants.
- To determine if the timing of benzodiazepine exposure (by trimester) influences these risks.
Main Methods:
- A 13-year longitudinal cohort study using Taiwan's National Health Insurance Research Database (2004-2016).
- Included population-wide, sibling, and paternal comparisons.
- Analyzed live births exposed or unexposed to benzodiazepine, with sibling controls for unexposed pregnancies by the same mother.
Main Results:
- Analysis of over 4.8 million births revealed significant increased risks for PTB (OR 1.71) and SGA (OR 1.47) solely among infants born to mothers exposed to benzodiazepine in the third trimester.
- No significant associations were found for benzodiazepine exposure during the first or second trimesters.
Conclusions:
- Third-trimester benzodiazepine exposure is linked to increased risks of PTB and SGA.
- Findings may indicate direct effects of benzodiazepines on fetal development or the intrauterine environment.
- Unmeasured confounders like smoking and parental mental illness severity were limitations.
Background:
Intrauterine exposure of the developing fetus or neonate to bendodiazepine may lead to fetal abnormalities or adverse reactions. We sought to investigate whether benzodiazepine use before or during different trimesters of pregnancy had different associations with incident preterm births (PTB) or small for gestational age (SGA) infants.
Methods:
We conducted a 13-year longitudinal cohort study incorporating population-wide, sibling, and paternal comparisons. We used nation-wide population-based data on diagnoses and drug prescriptions from the Taiwan National Health Insurance Research Database, with linkages to the Taiwan Birth Certificate Registration and the Taiwan Maternal and Child Health Database between 2004 and 2016. We obtained data on live births to mothers exposed or unexposed to benzodiazepine. Children born by the same mother without benzodiazepine exposures before or during pregnancy were ascertained to create the sibling comparison cohort. We also gathered information on newborns with benzodiazepine-exposed or unexposed fathers. We determined the risks of subsequent PTB and SGA during the 13-year follow-up period.
Results:
We included data on 2 572 125 births to mothers exposed to benzodiazepine and 2 265 685 births to mothers unexposed to benzodiazepine. After adjustments and from our sibling comparison group, the increased risks of preterm births (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.53-1.91) and SGA (OR 1.47, 95% CI 1.14-1.89) were significant only among children born from mothers exposed to benzodiazepine in the third trimester.
Limitations:
Our results are subject to unmeasured confounding factors, such as smoking and the severity of parental mental illness, which were not available in the administrative claims data.
Conclusion:
Benzodiazepine exposure during the third trimester, but not the first or second trimesters, increased the risks of PTB and SGA. This result may reflect the direct effects of benzodiazepine on fetal development or the intrauterine environment.
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