ABSTRACT
Infants exposed in utero to antiepileptic drugs showed significantly more behaviour disturbances such as sedation (p less than 0.05) and hyperexcitability (p less than 0.01) than infants of a control group. The presence of these clinical symptoms and the time of their appearance did not seem to be dependent on the type of maternal medication, nor on the drug serum concentration in cord blood nor on the rate of drug disappearance from the infant's plasma.
Subject(s)
Anticonvulsants/adverse effects , Child Behavior Disorders/chemically induced , Epilepsy/drug therapy , Infant, Newborn, Diseases/chemically induced , Pregnancy Complications/drug therapy , Akathisia, Drug-Induced , Anticonvulsants/therapeutic use , Female , Humans , Infant, Newborn , Pregnancy , Prospective Studies , Sleep/drug effects , Time Factors , Tremor/chemically inducedABSTRACT
In a prospective controlled study 70 children of females with epilepsy and on anticonvulsant medication during pregnancy were investigated. It was shown that epileptic females had stillbirths more frequently than expected. After delivery particularly children on phenobarbitone are sedated. Due to weak suckling this may lead to inadequate food intake. Withdrawal symptoms manifest in affected children as hyperexcitability lasting for weeks. Children of epileptic women on medication are generally smaller, of lower weight and have smaller heads than children from all control groups. Ingestion of more than one anticonvulsant leads to an even more pronounced reduction of infantile body measurements below the expected mean value. Small malformations are observed more frequently after intrauterine exposition to anticonvulsants than in the control groups. Ingestion of more than one anticonvulsant leads to an increase of the number of small malformations in the child than after single drug therapy. Children of epileptic parents are affected more frequently by large malformations than children of nonepileptic parents.
Subject(s)
Anticonvulsants/adverse effects , Epilepsy/drug therapy , Pregnancy Complications/drug therapy , Prenatal Exposure Delayed Effects , Abnormalities, Drug-Induced/diagnosis , Abortion, Spontaneous/chemically induced , Adult , Akathisia, Drug-Induced , Anencephaly/chemically induced , Craniofacial Dysostosis/chemically induced , Female , Fetal Growth Retardation/chemically induced , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Infant, Newborn, Diseases/chemically induced , Maternal-Fetal Exchange , Phenytoin/therapeutic use , Pregnancy , Primidone/therapeutic use , Substance Withdrawal Syndrome/etiology , Uterine Cervical Incompetence/chemically induced , Valproic Acid/therapeutic useABSTRACT
Fourteen epileptic women treated with primidone, either alone or in combination with other antiepileptic drugs, were studied prospectively during their pregnancy. Plasma levels of primidone and its metabolites were monitored and correlated to findings in the offspring. Maternal serum concentrations of primidone and metabolites were generally low during pregnancy. The levels of its main metabolites--phenobarbital and PEMA--were found to drop within the first month of pregnancy in two cases. The plasma concentrations remained low until birth and rose sharply thereafter. The phenobarbital/primidone ratio (mean 0.84) and PEMA/primidone ratio (mean 0.56) in pregnant patients were found to be lower than in non-pregnant patients, except when primidone was given in combination with phenytoin in which case the expected phenobarbital/primidone (mean 2.5) and PEMA/primidone (mean 1.5) ratios were found. A ventricular septal defect was found in one of the offspring of the fourteen mothers and five children had microcephaly. There was a high incidence of poor somatic development with dystrophy (n=3) and short stature (n=2). Head circumferences (n=8), lengths (n=4) and/or weights (n=8) were below the 10th percentile in a number of children. Four children showed marked facial dysmorphy. Our preliminary data suggest that primidone intake during pregnancy may be important in the pathogenesis of minor anomalies and in the induction of poor somatic development.