Neurodevelopment in Late Infancy After Prenatal Exposure to Benzodiazepines - A Prospective Study*

Abstract

Growth and neurodevelopment at 6, 10 and 18 months of age have been studied prospectively and longitudinally in a series of 17 children born to mothers who used benzodiazepines (BZD) in therapeutic doses as their only psychotropic drug throughout pregnancy. The results were compared with a group of 29 children born to mothers without any known use of psychotropic drugs. The BZD-exposed children caught up their low mean birth-weight, at an early stage, whereas the slightly decreased head circumference at birth remained at the same low level. In five infants, a pattern of craniofacial anomalies was found. Deviating neurodevelopmental and clinical symptoms and signs were common. The gross motor development was retarded at 6 and 10 months, but was nearly normal at 18 months. Impaired fine motor functions were found on all follow-up occasions. At 18 months, the most prominent finding was a delayed development of pincer grasp. The BZD-exposed children showed deviations in muscle tone and pattern of movements more frequently than children in the reference group. The study suggests that the use of BZD in therapeutic doses throughout pregnancy can have negative effects on the development of children up to 18 months of age. The long-term hazards cannot be evaluated from these results. A further follow-up at early school age is needed and is in progress.

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

“…The clinical findings of this BZD syndrome included Möbius syndrome, Dandy-Walker malformation with lissencephaly, polycystic kidney, submucous cleft hard palate, microcephaly, dysmorphism, varying degrees of mental retardation, convulsions, and neonatal abstinence syndrome (Gerhardsson and Alfredsson, 1987). Low birth weight and small head circumference were also reported in a study of 17 infants born of women who had taken diazepam or other BZDs during pregnancy (Laegreid et al, 1992b). The weight of children returned to normal values by 10 months, but head circumference was still smaller than expected at 18 months (Laegreid et al, 1992a).…”

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017

“…An early longitudinal case-control study suggested that exposure to meprobamate or chlordiazepoxide (n=1870) had no adverse effects (Hartz et al, 1975), but a small (n=17) follow-up study of children exposed to various benzodiazepines suggested early (up to 18 months) motor and wider developmental delay (Laegreid et al, 1992;Viggedal et al, 1993). A more recent Danish regional prescription register study suggested in utero benzodiazepine (and antidepressant and antipsychotic) exposure is possibly associated with an increased risk of delayed psychomotor development (Mortensen et al, 2003).…”

Antiepileptic drugs and neurodevelopment

“…A multinational European survey in 1987 of 577 infants with in utero exposure to monotherapy with AEDs showed increased incidence of congenital malformations with all AEDs but a doubling of risk with the use of valproate [16]. In 1997, pooled data from five prospective European studies totaling 1379 children (1221 exposed in utero and 158 unexposed control subjects) indicated an increased risk of MCMs with a relative risk of 2.3, in particular with valproate (dose dependent) and carbamazepine, or polytherapy with other (older) AEDs [17].…”