Teratogenicity of debendox and pyrimethamine.
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Biomedical subjects
Publications and source records attributed to S Sheppard.
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In accordance with a previous protocol, a second cohort of 254 mothers with a history of previous neural tube defect (NTD) births was before a subsequent conception and continued until the time of the second missed menstrual period. There were 2 NTD recurrences (0.9% of 234 infants/fetuses examined), which is significantly fewer than the 11 NTD recurrences (5.1% of 215 infants/fetuses examined) born to 219 unsupplemented (US) mothers in the same centres over the same period. When the data for the two cohorts were combined, the overall recurrence rates were 0.7% for 454 fully supplemented (FS) mothers and 4.7% for 519 US mothers. The recurrence rates after 1 previous NTD were 0.5% for FS and 4.2% for US mothers: after 2 or more previous NTDs, 2.3% for FS and 9.6% for US. There were no recurrences among the offspring of a further 114 mothers whose duration of supplementation fell short of the full regimen (partially supplemented, PS).
1. We measured erythrocyte folic acid and riboflavin, serum folic acid and leucocyte vitamin C in women at high risk for neural tube defect (NTD) recurrence who were receiving periconceptional vitamin supplementation, before they received extra vitamins, after 28 d of supplementation and at the 8th week of pregnancy. Blood vitamin concentrations in unsupplemented high-risk women were also compared with the values found in unsupplemented low-risk women. 2. Vitamin supplementation with Pregnavite Forte F (Bencard) raised the mean values for all vitamins measured by the 8th week of pregnancy. Mean erythrocyte folic acid rose from 250 to 478 ng/ml; plasma folic acid from 8.4 to 26.1 ng/ml; leucocyte vitamin C from 1.82 to 3.21 micrograms/ml blood; erythrocyte riboflavin (glutathione reductase (EC 1.6.4.2) activation ratio) from 1.08 to 1.04. All women receiving supplements had increased their serum and erythrocyte folic acid levels above the highest values found in women in an earlier study, who subsequently gave birth to children with NTD. Not all women, however, increased their leucocyte ascorbic acid or erythrocyte riboflavin levels above the highest values. 3. When vitamin concentrations in unsupplemented high-risk women compared with levels in unsupplemented women at low risk for NTD, no significant differences were found in the mean values. However, a significantly higher proportion of high-risk compared with low-risk women had erythrocyte folic acid and leucocyte vitamin C values on or below the 5th percentile of the adult normal range. 4. The effectiveness of Pregnavite Forte E (Bencard) for increasing maternal vitamin reserves is discussed with a view to preventing NTD and the possibility of identifying groups at risk for NTD because of low blood vitamin levels is considered.
Mean daily folate intakes of 195 women in the first trimester of pregnancy were assessed by 5-7 day weighed dietary records. Intakes for total folate ranged from 64.7 to 302.0 micrograms/day with a mean intake of 148.0 micrograms/day. The lowest intakes were associated with social classes III, IV and V, maternal age less than 20 years and vomiting on three or more days per week.
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An earlier preliminary paper is expanded. Women who had given birth to one or more infants with a neural tube defect were recruited into a trial of per conceptional vitamin supplementation. Two hundred mothers attending five centres were fully supplemented (FS), 50 were partially supplemented (PS), and 300 were unsupplemented (US). Neural tube defect recurrences in the study pregnancies were 1 (0.5%), in FS, none in PS, and 13 (4%) in US mothers. The difference in outcome between FS and US mothers is significant. The most likely explanation is that supplementation has prevented some neural tube defects, but further studies are needed.
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Women who had previously given birth to one or more infants with a neural-tube defect (NTD) were recruited into a trial of periconceptional multivitamin supplementation. 1 of 178 infants/fetuses of fully supplemented mothers (0.6%) had an NTD, compared with 13 of 260 infants/fetuses of unsupplemented mothers (5.0%).
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We investigated the incidence of birth defects in the offspring of women who took Bendectin during pregnancy. Copies of all prescriptions issued for Bendectin in two Cities, Leeds and Liverpool, over periods of 12 and 14 months, respectively, were scanned and a record initiated for each patient. Birth notifications were later searched for matching with indexed patients. Births were traced for 2,298 patients and the incidence of major defects compared with those in the relevant populations. We found no evidence to suggest that Bendectin is teratogenic in humans.
1. Leucocyte ascorbic acid concentrations have been measured in 1147 females during early pregnancy and in smaller numbers of women before conception, throughout pregnancy and at 6 months post partum. 2. The leucocyte concentration in the 1st trimester was found to be affected by season, social class and smoking. Selecting individuals by extremes of social class, season and smoking produced two small populations with almost separate ascorbic acid distributions and mean concentrations of 21.7 and 45.1 microgram/10(8) leucocytes. 3. Early pregnancy had little effect on leucocyte ascorbic acid concentrations but values decreased in the second trimester. However, this was associated with a leucocytosis so that the total leucocyte ascorbic acid content of blood was unchanged. 4. Low ascorbic acid concentrations during the 1st trimester were not associated with subsequent spontaneous abortions, still-births or neonatal deaths, but there was an increased frequency of low values in women who gave birth to infants smaller than 3250 g. 5. The adequacy of ascorbic acid reserves in early pregnancy is discussed.
1. Mean daily nutrient intakes of 195 women in the first trimester of pregnancy were assessed by weighed dietary records. 2. In comparsion with recommended intakes for non-pregnant women aged 18-55 years (Department of Health and Social Security, 1969), more than two-thirds of the subjects were having insufficient energy, iron and cholecalciferol. Unsatisfactory intakes of other nutrients were not uncommon. In relation to recommended intakes for the second trimester (Department of Health and Social Security, 1969), all mothers were having insufficient cholecalciferol and more than 80% of mothers had unsatisfactory intakes of energy and Fe. 3. Intakes appreciably lower than those recommended were associated with the following factors: social classes III, IV and V; maternal age under 20 years; smoking ten or more cigarettes daily; vomiting on more than 3 d/week.
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Data from the National Congenital Rubella Surveillance Programme showed that 44% of children with congenital rubella reported to the programme were born to primiparae. This high proportion is thought to be due to the fact that there was a two-fold increase in the rate of abortion for rubella in pregnancy for women with two or more children. This higher incidence of congenital rubella in firstborns emphasises the need for rubella vaccination prior to a woman's first pregnancy.
Serum folate, red cell folate, white blood cell vitamin C, riboflavin saturation index, and serum vitamin A were determined during the first trimester of pregnancy in over 900 cases. For each of these there was a social classes I + II showed the highest levels which differed significantly from other classes, except for serum folate. In 6 mothers who gave birth to infants with neural tube defects, first trimester serum folate, red cell folate, white blood cell vitamin C, and riboflavin values were lower than in controls. In spite of small numbers the differences were significant for red cell folate (P less than 0-001) and white blood cell vitamin C (P less than 0-05). These findings are compatible with the hypothesis that nutritional deficiencies are significant in the causation of congenital defects of the neural tube in man.