Benzodiazepine Use Decreases Infant Birth Weight

Anders Huitfeldt, MBBCh, BAO, ScD

New study findings suggest benzodiazepine or benzodiazepine-like hypnotic use during pregnancy is associated with a mean decrease in birth weight of 79 g.

Although the magnitudes of the findings had no obvious clinical relevance, study authors determined the drugs should only be used in pregnancy after a thorough evaluation of the benefits and risks for the mother and child.

Anders Huitfeldt, MBBCh, BAO, ScD, and a team of investigators aimed to determine whether exposure to benzodiazepines or benzodiazepine-like hypnotics in pregnancy was associated with greater risk of negative immediate pregnancy outcomes compared with non-exposure. The colleagues based the study on the Norwegian Mother, Father, and Child cohort study which used data from the Medical Birth Registry of Norway. They recruited pregnant women from Norway from 1999-2008. The study cohort included 114,500 children, 95,200 mothers, and 75,200 fathers. The investigators included 82,038 pregnancies in the primary analyses and 19,554 women who experience mental health or sleeping issues before or during pregnancy in a secondary analysis.

Data on self-reported drug use was collected from Norwegian Mother, Father, and Child questionnaires 1, 3, and 4. Women were asked a range of disease-oriented questions such as whether they had had depression, anxiety, or mental disorders before or during pregnancy or sleeping problems during early pregnancy. Mothers gave information on whether medications were used in four-week intervals during pregnancy.

The primary outcomes were gestational age at delivery, risk of preterm delivery, birth weight, birth weight relative to gestational age and sex, and risk of being small for gestational age. Additional main outcomes included head circumference, Apgar scores less than 7 at 5 minutes, and risk of neonatal respiratory distress.

Huitfeldt and the team included 82,083 singleton pregnancies in women who completed all 3 questionnaires. The mean maternal age was 30.2 years while 45.9% of women were primiparous and 51.2% of infants were boys.

Among the women in the study, 679 (.8%) were exposed to benzodiazepines or benzodiazepine-like hypnotics during pregnancy. Compared to women who were not exposed, those who were exposed were older (mean age, 31.2 years old vs 30.2 years old), less likely to be married or cohabiting (90.4% vs 96.5%), more likely to be primiparous (52.4% vs 45.8%), more likely to smoke (16.5% vs 7.4%), and more likely to report low or moderate alcohol intake during pregnancy (4.1% vs 2.5%). Those who were exposed were also more likely to report illicit drug use (4.9% vs .6%), less likely to have a planned pregnancy (27.8% vs 82%), more likely to have depression (31.1% vs 6.5%), and more likely to have had at least 1 painful or very painful adverse life event (57% vs 34.9%).

Use of benzodiazepine or benzodiazepine-like hypnotics during pregnancy was linked with lower birth weight (mean difference, -79.3 [95% CI, -126.7 to -31.9] g), lower gestational age at birth (mean difference, -2.1 [95% CI, -3.3 to -0.9] days), and a higher risk of preterm birth (risk ratio, 1.41 [95% CI, 1.03 to 1.94]). There was no significant association of exposure with the child’s birth weight relative to gestational age and sex or any other immediate birth outcomes.

The association of exposure with birth weight could be explained by earlier delivery rather than impaired intrauterine growth, the investigators concluded.

The study, “Associations of Maternal Use of Benzodiazepines or Benzodiazepine-like Hypnotics During Pregnancy With Immediate Pregnancy Outcomes in Norway,” was published online in JAMA Network Open.