Apparent prevention of neural tube defects by periconceptional vitamin supplementation. 1981.

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 periconceptional vitamin supplementation. Two hundred mothers attending five centres were fully supplemented (FS), 50 were partially supplemented (PS), and 300 were unsupplemented (US).

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.

Investigation of folate intake and metabolism in women who have had two pregnancies complicated by neural tube defects.

Object: To investigate folate intake and blood levels of folic acid and vitamin C in women with and without a history of two NTD-affected pregnancies and to measure the increase in serum folate following ingestion of orange juice.

Subjects: Sixteen women with a history of two NTD-affected infants and 16 controls with no such history, none of whom were either pregnant or taking vitamin supplements. The orange juice loading test was carried out on eight matched pairs.

Immunisation of the preterm baby.

The study was designed to quantify the preterm baby's response to routine childhood immunisations. A total of 69 preterm babies were put into two groups according to their gestational age: less than 32 weeks and between 32 and 35 weeks. Within each group the babies were randomly placed into one of three schedules for immunisation with diphtheria, tetanus, pertussis and oral poliomyelitis vaccines at 3, 4 and 5 months; 3, 4, 5 and 18 months; and 3, 4 and 10 months.

Investigation of factors influencing folate status in women who have had a neural tube defect-affected infant.

Objective: To investigate folate intake and blood levels of vitamins in women with and without a history of neural tube defect (NTD)-affected infant and to explore the relation between red cell and serum folate in those women.

Subjects: Twenty-nine women with a history of NTD-affected infant, who had taken periconceptional vitamin supplements one year or more prior to the study and twenty-nine controls with no such history.

Main Outcome Measures: Dietary intake of folate was assessed by questionnaire and blood levels of folate, vitamin B12 and vitamin C were measured.

Uptake and utilization of DL-5-[methyl-14C] tetrahydropteroylmonoglutamate by cultured cytotrophoblasts associated with neural tube defects.

A significant advance in the primary prevention of neural tube defects (NTD) is the recent finding that the periconceptional supplementation with folate has a 72% preventive effect against recurrence of NTD. However, failure of folate supplements to prevent all recurrences supports the multifactorial causation hypothesis, with inherited components exerting their influence, possibly through defects of storage, transport, or metabolism of folate. We have assessed the kinetics of DL-5-[methyl-14C]tetrahydropteroylmonoglutamate ([14C]MTHF) uptake and incorporation into the nucleic acid and protein pools by NTD-associated and control trophoblasts cultured in a medium lacking thymidine and other DNA precursors.

Delayed detection of congenital hearing loss in high risk infants.

Objective: To examine the methods used to investigate children at high risk of congenital hearing impairment, and to see whether the introduction of evoked response audiometry has reduced the mean age at which hearing loss is identified.

Design: Clinicians who notified children to the national congenital rubella surveillance programme were asked retrospectively to complete a questionnaire examining the methods used to identify hearing impairment and the age at testing in two consecutive five year cohorts. The presence or absence of hearing loss was confirmed by obtaining the results of audiometric evaluations and, whenever possible, a recent pure tone audiogram.

Multiple abnormalities in a child with partial duplications of 10p and 13q from a 3:1 segregation of a maternal t(10;13) translocation.

Partial duplications of 10p and 13q in association with partial deletions of other chromosome segments have been variously reported. We describe here a female child with multiple congenital abnormalities and combined partial duplications of 10p and 13q resulting from a 3:1 segregation of a maternal t(10;13)(p13;q22). In comparing the phenotypic features of the two chromosome imbalances, the expression of features typical of partial duplication 10p appeared more pronounced.

Onset and severity of hearing loss due to congenital rubella infection.

Of 111 children born in 1978-82 with congenital rubella infection, confirmed by the detection of rubella specific IgM shortly after birth, 68 were reported to be hearing impaired when notified to the National Congenital Rubella Surveillance Programme (NCRSP). The average age at which the diagnosis of hearing impairment was confirmed was 11.6 months.

Biotransformation of pteroylmonoglutamic acid during absorption: implications of Michaelis-Menten kinetics.

Previously reported work from this laboratory has shown that, in man, the formation of plasma 5-methyltetrahydrofolic acid (5MeTHF) from orally administered pteroylmonoglutamic acid (PGA) obeys Michaelis-Menten kinetics. The regression equation obtained from a plot of the reciprocal amount of 5MeTHF formed (micrograms per litre plasma/min) as a function of reciprocal amount of PGA administered (micrograms/kg body weight) provides a useful means of calculating the improved efficiency of 5MeTHF formation by dividing the total dose of PGA into smaller doses.

In vivo characterization of the absorption and biotransformation of pteroylmonoglutamic acid in man: a model for future studies.

HPLC-EC has been used to measure the appearance of 5-CH3-H4 folic acid in human plasma following oral administration of folic acid. The process was found to be saturable in accordance with Michaelis-Menten kinetics. The apparent Km for this enzyme system indicates that low doses of oral folic acid are rapidly converted into 5-CH3-H4 folic acid, an observation consistent with the needs of intestinal absorption of essential trace nutrients.

Prevalence of neural tube defects in the Yorkshire Region.

The birth prevalence of neural tube defects (NTD) in the Yorkshire Region was determined for 1985 and 1986 by ascertainment of cases in live-and stillborn babies and of pregnancies terminated for NTD. Sixty-seven cases of anencephaly, 82 of spina bifida and 11 others were identified, a prevalence of 1.54 per 1000 total births.

Neural tube defect recurrence after 'partial' vitamin supplementation.

A total of 227 mothers enrolled for periconceptional multivitamin supplementation because of previous neural tube defect (NTD) births took vitamins for less than the recommended minimum period (at least 28 days before conception until two menstrual periods have been missed). Of 213 examined infants/fetuses born to these partially supplemented mothers, two had NTD, one of whom followed four previous NTDs. The observed NTD recurrence rate is similar to that observed in fully supplemented mothers.