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.

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The biliary tract has been prospectively studied in a consecutive series of 769 patients undergoing surgery for gallstones to determine whether differences exist between subjects with and without a history of acute pancreatitis. The incidence of acute gallstone pancreatitis (AGP) was 7.7 per cent and men with gallstones were significantly more likely to develop pancreatic inflammation. Operations on patients with AGP were accompanied by a higher mortality rate which was almost entirely due to the severity of the disease at the time of surgery. The earlier operations were performed after the onset of pancreatitis the more often stones were found in the common bile duct and at the ampulla. Patients with AGP had smaller and more numerous gallbladder stones in association with a wider cystic duct that controls. The common bile duct diameter in patients with AGP was independent of the presence of choledochal calculi implying either previous temporary obstruction to the biliary tree or a dilated duct ab initio. Pancreatic duct reflux was far more commonly observed on the cholangiograms of patients with AGP and in these patients reflux occurred into a wider pancreatic duct, at a greater angle and was associated with a longer functioning common channel. No patient developed recurrent pancreatitis following biliary surgery. These features strongly support the concept of gallstone migration and suggest that patients with gallstones who develop acute pancreatitis have essential differences in their biliary tree which mechanically facilitate migration of calculi.