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. SETTING: The United Kingdom. PATIENTS: Children notified to the national congenital rubella surveillance programme and born in 1978-87 in whom IgM specific for rubella was detected shortly after birth. MAIN OUTCOME MEASURES: The age at which hearing loss was identified and the degree of loss in decibels at 250, 500, 1000, 2000, and 4000 Hz measured by pure tone audiometry. RESULTS: 61 (52%) Of 117 children born in 1978-82 had a hearing impairment of 40 dB or greater in both ears. The mean loss was 93 dB. In the following five years 75 (47%) of 159 children had impaired hearing, their mean loss being 96 dB. The age at which the hearing loss was confirmed decreased from 11.6 to 9.8 months as a result of earlier auditory evoked response testing. Nevertheless, only eight (13%) of the children with hearing impairment born in 1978-82 and 16 (21%) of those born in 1983-7 had these tests performed in the first six months of life. CONCLUSIONS: Unacceptable delays in identifying hearing loss occurred in this high risk group because of failure to arrange auditory evoked response testing in early infancy. Evoked response audiometry is sensitive and specific and should be undertaken within the first few months of life for all infants known to be at risk of sensorineural hearing loss.

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). 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.

The challenges of teratology.

Teratology has its origins in the descriptive anatomy of malformed humans. Although the term now has much wider connotations, the first challenge of teratology is to recognise its purpose as a science related to a human problem. The wider connotations inevitably mean the involvement of increasing numbers of disciplines, each with its own language and limitations, but each with a unique contribution to make. The second challenge of teratology is therefore to establish and expand communications between these disciplines. The third challenge is teratogenesis, which requires a rather more profound consideration of the nature of causation than a simple cause-and-effect relationship. At the same time as looking back from consequences to causes, we must look forward from the causes to alternative consequences. The affinity of teratogenesis, carcinogenesis, and mutagenesis constitutes the fourth challenge. The fifth challenge brings us back to humans, and lies in the relationships between scientists working within the field of teratology, and industry, the law, the media, and the public at large.

Defects and disabilities of thalidomide children.

The range of defects and disabilities in thalidomide children is very much wider than is generally realized. The defects of 154 children are described and classified. Their disabilities range from incapacitating to negligible.

Oral contraceptives and birth defects.

PIP: Although OCs (oral contraceptives) are not designed to be taken during pregnancy, in Europe and the U.S. they are taken by 2-5% of women in early pregnancy and by 1/4-1/3 of women 3-4 months prior to conception. The effects of OCs on folic acid and other vitamin metabolism are well known and provide a theoretical basis for possible teratogenicity, even when stopped prior to conception. Both hormone support therapy for threatened abortions and hormonal pregnancy tests have been abandoned in recent years, the first because it proved inefficacious, the second because there are better alternatives available. In neither of these cases were sex hormones shown to be teratogenic. Most cohort (prospective) and many case-control (retrospective) studies have shown no association between OC use and birth defects. Case-control methodology can be criticized because of recall bias and because of the difficulty of choosing entirely matched controls. Several studies have shown OC users to have characteristics slightly different from the general population, e.g., they are younger, more often unmarried, and are more likely to smoke during pregnancy. Any of these characteristics might influence the occurrence of teratogenicity. It is impossible to prove that OCs constitute a low-level teratogen. The author considers them nonteratogenic.^ieng

Teratogenicity testing in humans: a method demonstrating safety of bendectin.

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.

Poliomyelitis-like illness after acute asthma.

Two children had pain in one arm, followed by weakness and wasting, after an acute exacerbation of bronchial asthma. Similar cases in which a poliomyelitis-like illness was associated with acute asthma have been reported, but the relationship between the two remains conjectural.

A rapid and specific HPLC-electrochemical method for the determination of endogenous 5-methyltetrahydrofolic acid in plasma using solid phase sample preparation with internal standardization.

A rapid and specific HPLC-electrochemical method for determining endogenous 5-methyltetrahydrofolic acid (5MeTHF) in plasma is described. Quantitative solid phase extraction of 5MeTHF and internal standard, beta-hydroxyethyltheophylline, was carried out using proprietary phenyl bonded-silica columns (Bond Elut Phenyl cartridges, 1.0 mL capacity). Chromatographic separation was achieved using a mobile phase consisting of 15% (v/v) methanol in 0.05 M KH2PO4, pH 3.5 at a flow rate of 2.0 mL/min in conjunction with a Waters Assoc. radially compressed Nova-Pak phenyl column (10 cm x 8 mm, 4 microns bonded silica). The internal standard was measured by UV detection at 254 nm. A Bioanalytical Systems Inc. LC-17 glassy carbon oxidative flow cell with a potential held at +0.35 V vs Ag/AgCl using the LC-4A amperometric controller allowed levels of 1-2 ng/mL 5MeTHF to be measured in 500 microL of plasma. Daily appraisal of the ratio produced by authentic materials clearly demonstrated that quantitation using dual detection was not subject to problems of differential response. Inter-day variation of the differential detector response is cited. Comparison of the Lactobacillus casei bioassay with HPLC demonstrates good agreement between methods but at the same time highlights the drawback of using such non-specific methods to measure samples where more than one folylmonoglutamate may be present. Antoxidant free storage for three months at -70 degrees C in darkness resulted in no deterioration of 5MeTHF. A comparison of the means and range of values for plasma folate obtained using HPLC, L. casei bioassay and the radiometric binding assay is reported.

Vitamin A, pregnancy, and oral contraceptives.

It has been shown that women receiving oral contraceptives have increased levels of serum vitamin A. High vitamin A levels may constitute a teratogenic hazard and it has been suggested that women who conceive soon after discontinuing oral contraceptive therapy may be especially at risk to this hazard.We have confirmed a significant increase in vitamin A levels in women taking oral contraceptives. During early pregnancy there is no significant difference in vitamin A levels between women who have recently been taking oral contraceptives and those who have not. We have been unable to show that either taking oral contraceptives shortly before pregnancy or a high vitamin A level during the first trimester of pregnancy, comparable to that of a woman taking oral contraceptives, has any detrimental effect on the outcome of pregnancy. It seems unlikely that women who conceive soon after discontinuing oral contraception run any teratogenic risk from increased vitamin A levels.

Weber-Christian panniculitis.

Two cases of Weber-Christian panniculitis with onset at 7 months and 3 years 6 months are described. Both show evidence of disturbances in immune mechanisms. The family of the first case has a high prevalence of coeliac disease, and the mother of the first patient also suffers from alopecia areata and dermatitis herpetiformis.

The effects of maternal folic acid and vitamin C nutrition in early pregnancy on reproductive performance in the guinea-pig.

1. The effect of different intakes of folic acid (FA) and vitamin C on pregnancy in the Dunkin-Hartley guinea-pig was examined. Female guinea-pigs were subjected to three graded intakes of FA and vitamin C ('deficient', 'intermediate' similar to recommended daily intakes (RDI), and 'supplemented') during early gestation and up to the time of neural tube closure (17th day of gestation), and then returned to the RDI of these vitamins. 2. Plasma and blood cell concentrations of these vitamins were measured once before and at the end of the dietary treatments. Reproductive performance was assessed in terms of the number of resorbed and aborted embryos and weight and size of the live fetuses on the 36th day of gestation. 3. The short-term deficiency of either of these two vitamins, insufficient to affect maternal health, had a dramatic effect on the reproductive performance. 4. The RDI of FA was significantly less effective than the supplemented intake in preventing embryonic deaths. The RDI of vitamin C produced lighter and smaller live fetuses than the supplemented intake. 5. The implications of these findings with regard to vitamin status in early pregnancy in man are discussed.