Advantages and problems with pregnancy registries: observations and surprises throughout the life of the International Lamotrigine Pregnancy Registry.

PURPOSE: The International Lamotrigine Pregnancy Registry monitored for a signal of a substantial increase in the frequency of major congenital malformations associated with lamotrigine exposures in pregnancy over an 18-year period. Key methodological lessons are discussed. METHODS: The strengths and weaknesses of the Registry were assessed using quantifiable methodological and operational parameters including enrollment, completeness of exposure and outcome data reporting, and lost to follow-up. The choice of comparator groups and stopping rules for registry closure were critically evaluated. RESULTS: The reliance on voluntary reporting was associated with a clustered geographical distribution of registered pregnancies. The enrollment rate increased over time with new approvals and indications for lamotrigine and publication of interim data. Reporter burden was minimized through a streamlined data collection approach resulting in a high level of completeness of exposure and primary outcome data. Lost to follow-up rates were high (28.5% overall) representing a major limitation; incentives to increase the completeness of reporting failed to reduce rates. A lack of an internal comparator group complicated data interpretation; but external comparisons with multiple external groups allowed an assessment of consistency of outcome data across multiple data sources. A lack of a priori closure criteria prolonged the life of the Registry, and consideration of regulatory guidelines on this subject is encouraged at the time of conception of future registries. CONCLUSIONS: A successful pregnancy exposure registry requires ongoing flexibility and continuous re-assessment of enrollment, recruitment, and retention methods and the availability of comparison data, throughout its lifecycle.

Current Concepts of Maternal Nutrition.

BACKGROUND: A nutrient-rich maternal diet before and during pregnancy is associated with improved fetal health, more appropriate birth weight, and increased rates of maternal and infant survival. Physicians need a better understanding of the role of diet in shaping fetal outcomes. Given this background, we reviewed and summarized articles on maternal nutrition found in MEDLINE since 1981, written in English, and limited to human subjects. FOR THE OFFSPRING: Maternal diets high in sugar and fat lead to an increased incidence of metabolic syndrome, diabetes, and cardiovascular disease later in life. Folic acid should be supplemented prior to conception and continued through at least the first 28 days of fetal life to prevent neural tube defects, and vitamin C should be given to women who smoke to lower the incidence of asthma and wheezing in the children. Iodine deficiency is increasing, and iodine should be included in prenatal supplements. If the maternal hemoglobin is 7 g/dL or more, there is no evidence that iron supplementation is needed. Fish intake during pregnancy is protective against atopic outcomes, whereas high-meat diets contribute to elevated adult blood pressure and hypersecretion of cortisol. FOR THE MOTHER: Calcium supplementation lowers the risk of preeclampsia and hypertensive disease in pregnancy. CONCLUSIONS: Given the limits of our current knowledge, a diet rich in whole grains, fruits, vegetables, and selected fish is desirable for the best outcomes. Diets high in sugar and fat lead to higher rates of diabetes, metabolic syndrome, and cardiovascular disease. Folic acid, iodine, and calcium in all pregnant women and vitamin C in smokers are the only supplements so far shown to be of value for routine use. The physician treating a pregnant woman should be ready to advise a healthy diet for the benefit of the fetus.