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International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?

OBJECTIVES: To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. DESIGN: Retrospective cohort study of births monitored by birth defect registries. SETTING: 13 birth defects registries monitoring rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among liveborn infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review. MAIN OUTCOME MEASURES: Incidences and trends in rates of neural tube defects before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable). RESULTS: The issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects. CONCLUSIONS: Recommendations alone did not seem to influence trends in neural tube defects up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of neural tube defects preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements.

Abortion, Induced↗

Pregnancy after breast cancer: population based study.

OBJECTIVES: To identify women who survived breast cancer and subsequently conceived and to determine the rate of pregnancy (proportion), management, outcome of the cancer, and outcome of the first subsequent pregnancy. DESIGN: Population based descriptive study with cases identified from the Western Australian data linkage system and validated by review of medical charts. Supplementary data obtained from hospital and clinician records. SETTING: Western Australia, 1982-2003. PARTICIPANTS: Women aged <45 with a diagnosis of breast cancer who subsequently conceived. MAIN OUTCOME MEASURES: Pregnancy outcome and rate, survival, time from diagnosis to pregnancy. RESULTS: Sixty two (54%) women with a diagnosis of breast cancer who subsequently conceived did so less than two years after their diagnosis: 29 of them had an abortion, 27 had a live birth, and six miscarried. Within a proportional hazards regression model subsequent pregnancy was associated with improved overall survival (hazard ratio 0.59, 95% confidence interval 0.37 to 0.95). When the model was stratified by time from diagnosis subsequent pregnancy was associated with improved overall survival in women who waited at least 24 months to conceive (0.48, 0.27 to 0.83) and a non-significant protective effect was seen for women who waited at least six months to become pregnant. CONCLUSIONS: Our study does not support the current medical advice given to premenopausal women with a diagnosis of with breast cancer to wait two years before attempting to conceive. This recommendation may be valid for women who are receiving treatment or have systemic disease at diagnosis, but for women with localised disease early conception, six months after completing their treatment, is unlikely to reduce survival.

Adolescent↗

Increased periconceptual maternal glycated haemoglobin in diabetic mothers reduces fetal long axis cardiac function.

OBJECTIVE: To compare ventricular long axis function in fetuses of diabetic mothers (FDM) with contemporaneously studied normal controls (N) and to assess the effect of pre-pregnancy diabetic control on these measurements. DESIGN: Long axis function was compared in 41 FDM and 159 N fetuses in a cross sectional observational study. SETTING: Fetal medicine unit. METHODS AND RESULTS: Echocardiography confirmed structural normality. Pulsed wave valvar Doppler velocimetry, lengthening and shortening myocardial velocities, and amplitude of ventricular long axis movement were recorded at the base of the left and right ventricular free walls and septum. Periconceptual diabetic control was assessed by haemoglobin A1c (HbA1c) in early pregnancy. Doppler and myocardial velocities were negatively related and myocardial thickness was positively related with HbA1c. In both cohorts all variables except mitral and tricuspid late filling (A wave) velocities were dependent on gestational age. FDM gestational age related values were higher for most variables and robust analysis of covariance showed significantly different maturation patterns in mitral valve E:A ratio (p = 0.036) and pulmonary velocity (p = 0.04), late lengthening myocardial velocities (left p = 0.016 and right p = 0.066), left myocardial shortening velocities (p = 0.008), and left free wall (p = 0.03) and septal (p = 0.04) amplitude of motion. FDM septal thickness was significantly increased throughout gestation (p < 0.0001). CONCLUSION: Periconceptual diabetic control influences fetal cardiac performance and myocardial hypertrophy but, unlike the pathophysiology of adult ventricular hypertrophy, is accompanied by functional adaptation. It is unlikely to explain the increased rate of late stillbirth observed in diabetic pregnancies.

Adult↗

Periconceptional vitamin supplementation and neural tube defects; evidence from a case-control study in Western Australia and a review of recent publications.

STUDY OBJECTIVE: The aim was to assess the association of neural tube defects with periconceptional vitamin supplementation. DESIGN: This was a matched, population based case-control study. SETTING: Western Australia, 1982-1984. PARTICIPANTS: Mothers of 77 cases (93% of those eligible) with isolated neural tube defects, mothers of 77 matched control infants with defects other than neural tube defects (control group I), and mothers of 154 liveborn, matched, control infants with no birth defects (control group II) participated in the study. MEASUREMENTS AND MAIN RESULTS: Information was collected by interview and self administered questionnaire. Crude and adjusted odds ratios (and their 95% confidence intervals) showed a small but non-significant protective effect of folate supplementation in comparisons with both control groups. The adjusted ratios for the three months before pregnancy were 0.69 (0.06, 8.53) with control group I, and 0.11 (0.01, 1.33) with control group II. In the first six weeks of pregnancy, the adjusted odds ratios were 0.70 (0.32, 1.52) with control group I and 0.74 (0.29, 1.88) with control group II. The odds ratios for vitamin supplementation of any kind were all very close to or greater than one, and all confidence intervals embraced unity. CONCLUSIONS: These data do not provide evidence of an association between periconceptional vitamin supplementation and neural tube defects, although a protective effect of folate supplementation cannot be excluded with confidence, due to the low power of the study. Of three other observational studies of vitamins and neural tube defects, two have shown an association. While further studies of this kind may be of value, evidence must now be sought from randomised controlled trials.

Case-Control Studies↗

Pregnancy in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age. Pregnancy and its outcome is a major concern to most SLE patients. Queries regarding the risk of disease flares during pregnancy, chance of fetal loss, and the safety of various drugs are often raised. With the improvement in the understanding of the pathogenesis of SLE and the judicious use of immunosuppressive drugs, better disease control can now be achieved and SLE patients should not be deprived of the opportunity for bearing children. Prepregnancy counselling and close collaboration with other specialists such as the obstetricians and the perinatologists is essential in optimising the maternal and fetal outcome in lupus pregnancies. In this review, important issues regarding the fertility rate, optimal timing of conception, risk of disease flares during lupus pregnancy, pregnancy course, fetal outcome, safety of various drugs used for disease control during pregnancy and lactation, and contraceptive advice are discussed.

Anti-Inflammatory Agents↗

Diabetic ketoacidosis in pregnancy.

The occurrence of diabetic ketoacidosis in pregnancy compromises both the fetus and the mother. It usually occurs in the later stages of pregnancy and is also seen in newly presenting type 1 diabetes patients. Despite improvement in its incidence rates and outcomes over the years, it still remains a major clinical problem since it tends to occur at lower blood glucose levels and more rapidly than in non-pregnant patients often causing delay in the diagnosis. This article illustrates a typical case of diabetic ketoacidosis in pregnancy and reviews the literature to provide an insight into its pathophysiology and management.

Adult↗

Knowledge on periconceptional use of folic acid in women of British Columbia.

OBJECTIVE: Our purpose was to evaluate the knowledge of folic acid and its use preconceptionally in women of British Columbia. METHODS: The study was conducted at British Columbia Women's Hospital in Vancouver, Canada, between April 15 and June 15, 1999. Pregnant women and women in the postpartum period were asked to complete a survey on folic acid. RESULTS: In total, 1,004 women completed the questionnaire during the study period. Seventy-one percent of the women knew that vitamins could help prevent birth defects. Of those, 76.3% identified folic acid as the one vitamin specifically associated with reduction of birth defects. It was identified that 49.4% of all women took vitamins prior to pregnancy. CONCLUSIONS: Women in the population studied were relatively well informed about the benefits of folic acid, but less than 50% of them took vitamins prior to conception.

Adult↗

Prevention and detection of diabetic embryopathy.

Congenital anomalies are more common in the offspring of women with type 1 and type 2 diabetes mellitus. Herein we define those anomalies more commonly found in the offspring of women with diabetes mellitus, and examine the role of hyperglycemia in their pathogenesis. We then discuss methods for the optimal screening and detection of embryopathy. We conclude by presenting evidence in support of preconception diabetes care to lower the risk of fetal anomalies in women with diabetes mellitus.

Journal Article↗