The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug (AED) treatments. A prospective cohort of women with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until six years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (6/50, 12.0%; aOR 6.05, 95%CI 1.65–24.53; p=0.007) and in those exposed to polytherapy with sodium valproate (3/20, 15.0%; aOR 9.97, 95%CI 1.82–49.40; p=0.005) compared to control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found amongst children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium valproate exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium valproate is a treatment option.

Purpose to determine the influence of epilepsy and its treatment on pregnancy and its outcome. Design controlled, observational study. Setting National Health Service maternity hospitals in Liverpool and Manchester regions. Population 277 women with epilepsy (WWE) and 315 control women. Methods WWE were recruited from antenatal clinics. Controls were matched for age and parity but not gestational age. Information was obtained by interview and from clinical records. Main Outcome Measures: obstetric complications, mode of delivery, condition of newborn. Results Distribution of epilepsy syndromes was similar to previous surveys. Most WWE (67%) received monotherapy with carbamazepine, sodium valproate or lamotrigine. Half WWE had no seizures during pregnancy but 34% had tonic clonic seizures. Seizure related injuries were infrequent. Pregnancies with obstetric complications were increased in women with treated epilepsy (WWTE 45%, controls 33%; p = 0.01). Most had normal vaginal delivery (WWTE 63%, controls 61%; p = 0.65). Low birth weight was not increased (WWTE 6.2%, controls 5.2%; p = 0.69). There were more major congenital malformations (MCM) (WWTE 6.6%, controls 2.1%; p = 0.02) and fetal/infant deaths (WWTE 2.2%, controls 0.3%; p = 0.09). Amongst monotherapies MCM prevalence was highest with valproate (11.3%; p = 0.005). Lamotrigine (5.4%; p = 0.23) and carbamazepine (3.0%; p = 0.65) were closer to controls (2.1%). There was no association between MCM and dose of folic acid preconception. Conclusion MCM were more prevalent in the babies of WWTE particularly amongst those receiving sodium valproate.

From the clinical data available, there is no indication that the risk of taking mefloquine in the first trimester of pregnancy is greater than that from any of the other antimalarials studied and the risk is considerably lower than that associated with falciparum malaria.

The purpose of this study was to evaluate the teratogenic potential of mefloquine (Lariam) in pregnancy, based on the Roche International Spontaneous Reporting System. Lariam is an anti-malarial drug used both in prophylaxis and treatment of malaria. Teratogenic effects were observed in animals but data from humans are lacking. Women of childbearing potential are currently advised to take contraceptive precautions up to three months after the last dose. The study included 1,627 spontaneous reports of women exposed to Lariam before or during pregnancy, which were received by Roche worldwide since introduction on the market. The data were analyzed considering pregnancy and fetal outcome and type of congenital malformations. The birth prevalence of congenital malformations in women exposed to Lariam is estimated to be 4% and is not different from the prevalence observed in the general population. In addition, the congenital malformations observed with Lariam exposure do not show any specific pattern. The data from our study suggest that the teratogenicity, which was observed in animals at high doses, cannot be applied to humans.

An attempt was made to estimate the risk of severe cutaneous adverse reactions (SCARs) to Fansidar (sulfadoxine plus pyrimethamine). Cases were identified through a spontaneous reporting system. Persons exposed were estimated using sales data of 27 countries reporting one SCAR case for either Fansidar or a related product, Bactrim (cotrimoxazole; sulfamethoxazole plus trimethoprim). Between 1974 and 1989, 126 cases were notified for Fansidar: 87 cases of erythema multiforme or Stevens-Johnson syndrome, and 39 cases of toxic epidermic necrolysis. 86% of cases were reported in Europe or North America. In 116 cases with use known, prophylaxis was the reason in 103, and treatment in 13. Toxic epidermolysis and erythema multiforme/Stevens-Johnson syndrome had case fatalities of 36 (95% confidence intervals 21 to 53%) and 9% (4 to 18%), respectively. Fansidar users were estimated at 117 million, and the overall SCAR risk to be 1.1 (0.9 to 1.3) per million. For developing countries with mainly single dose use, the risk was estimated to 0.1 (0.0 to 0.1) per million. For Europe and North America with mainly prophylactic use, the risk was 10 (8 to 12) and 36 (23 to 48) per million, respectively. Prophylactic use had a 40 times higher risk than single dose therapeutic use. The aggregated risk peaked in 1984-1985, with global and North American SCAR frequencies of 3.4 (2.4 to 4.3) and 72 (41 to 102) per million, respectively. After 1985, North America reported only one further case despite continued use by an estimated 0.3 million persons.(ABSTRACT TRUNCATED AT 250 WORDS)