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Biomedical subjects

N J Wald

Publications and source records attributed to N J Wald.

At least 145 records · Page 8Linked to original sources
PubMed1994

Folic acid and neural tube defects: the current evidence and implications for prevention.

The results of the MRC Vitamin Study have established the specific role of folic acid in the prevention of neural tube defects. Folic acid supplementation (4 mg/day) at the time of conception reduced the recurrence rate by about 70%. Evidence from observational studies and the Hungarian randomized trial (that used 0.4-0.8 mg/day supplemental folic acid) indicates that a similar level of prevention can be achieved among women who have not already had an affected pregnancy and that this may be achieved with a lower dose of folic acid. The medical implications of these results are important. (1) Women planning a pregnancy should take folic acid supplements. (2) Because a large proportion of pregnancies are unplanned and many of those that are planned will occur in women who will not have taken folic acid supplements, a complementary general public health strategy is needed, based on dietary advice and food fortification designed to achieve the benefit with adequate safety. (3) Any public health prevention strategy needs to be monitored for efficacy and possible harm. (4) Research is needed on the dose-response relationship between folic acid and neural tube defect prevention and the mechanism of action.

Dose-Response Relationship, Drug↗
PubMed1994

Value of maternal serum unconjugated oestriol measurement in prenatal screening for Down's syndrome.

We compared the medical and financial cost-effectiveness of prenatal serum screening for Down's syndrome using maternal age, serum alpha-fetoprotein and human chorionic gonadotrophin with and without the use of unconjugated oestriol. The use of unconjugated oestriol is medically more cost-effective than screening without it at all levels of detection. The actual performance depends on whether gestational age is estimated using 'dates' or an ultrasound scan. At a detection rate of 60 per cent, the proportion of unaffected fetal losses per case diagnosed at amniocentesis is about 22 per cent less if gestational age is estimated using dates (time since the first day of the last menstrual period) and about 47 per cent less if it is based on an ultrasound scan examination. At this detection rate, the inclusion of unconjugated oestriol increases costs by about 2k pounds per case diagnosed (36k pounds instead of 34k pounds) if gestational age is estimated using dates, but it is no more expensive if gestational age is measured from an ultrasound scan examination (indeed, it is more cost-effective at detection rates above 60 per cent). Since there is little change in the financial cost with the inclusion of unconjugated oestriol, for the improved medical performance of screening, it is worthwhile including it in the screening test.

Amniocentesis↗
PubMed1994

Four-marker serum screening for Down's syndrome.

The value of measuring the separate sub-units of human chorionic gonadotrophin (free alpha-hCG and free beta-hCG) instead of total hCG together with alpha-fetoprotein (AFP) and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples relating to 75 singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the serum sample, supplemented by data from 970 white women with unaffected pregnancies. Using the four serum markers AFP, uE3, free beta-hCG, and free alpha-hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, total hCG with maternal age). If gestation was based on an ultrasound scan examination, the detection rate was 72 per cent using the four serum markers compared with 67 per cent with the triple test. As an alternative illustration, if the detection rate was kept at 60 per cent and gestation was estimated by an ultrasound scan examination the four-marker test reduced the false-positive rate by one-third from 3 per cent using the triple test to 2 per cent with the four-marker test. Screening performance was hardly affected by adjusting marker levels for maternal weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1994

Maternal serum free alpha-human chorionic gonadotrophin levels in twin pregnancies: implications for screening for Down's syndrome.

Maternal serum free alpha-human chorionic gonadotrophin (free alpha-hCG) levels were determined in twin and singleton pregnancies at 15-22 weeks of gestation using a set of stored serum samples relating to 200 twin pregnancies and 600 singleton control pregnancies matched for gestational age and duration of storage. Free alpha-hCG values are, on average, 1.66 times greater in twin pregnancies than in singleton pregnancies (95 per cent confidence interval 1.56-1.76). If maternal serum free alpha-hCG is used in screening for Down's syndrome, values in twin pregnancies can be adjusted using this result so that screening can be performed in twin pregnancies as well as in singleton pregnancies.

Chorionic Gonadotropin↗
PubMed1994

Maternal serum free alpha- and free beta-human chorionic gonadotrophin in pregnancies with insulin-dependent diabetes mellitus: implications for screening for Down's syndrome.

A study was performed to investigate the concentrations of the alpha and beta free sub-units of human chorionic gonadotrophin (free alpha-hCG and free beta-hCG) in maternal serum between 15 and 22 weeks of pregnancy in 126 pregnancies among 92 women with insulin-dependent diabetes mellitus (IDDM). Each IDDM pregnancy was matched with two control singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar quarter). The median free alpha-hCG level in the IDDM pregnancies was 0.86 multiples of the median (MOM) for pregnancies without IDDM at the same gestational age (P < 0.002) (95 per cent confidence interval 0.80-0.94). The corresponding free beta-hCG level was 0.96 MOM (95 per cent confidence interval 0.85-1.09). These results enable free alpha-hCG values to be adjusted so that antenatal screening for Down's syndrome can be performed using this marker in IDDM pregnancies as well as in non-diabetic pregnancies.

Biomarkers↗
PubMed1994

Serum albumin and mortality in the BUPA study. British United Provident Association.

In the British United Provident Association (BUPA) study, a prospective observational study of 21,520 men, the serum albumin of 877 men who died during 10 years of follow-up was compared with that of 877 controls, each matched to a case by age (within 1 year) and date of attendance (within 3 months). There was little overall difference (mean case-control difference = -0.11 milligram, P > 0.2) despite the fact that other studies have reported a long-term association between low serum albumin and increased mortality. Cause-specific mortality data showed no association of low albumin with ischaemic heart disease or other circulatory diseases. An inverse association with cancer was confined to the first few years of follow-up and so attributable to pre-clinical cancer lowering both serum albumin itself and serum cholesterol, with which albumin was associated. There was an association of chronic respiratory, neurological, renal, liver and gut diseases with low serum albumin (case-control difference = -1.19 milligram, P < 0.001) consistent with the effect of pre-clinical disease lowering serum albumin. Other causes of death showed no association with albumin. Our data do not support a cause and effect association of low serum albumin and mortality.

Accidents↗
PubMed1994

Feasibility study of a randomised trial of ovarian cancer screening among the general population.

OBJECTIVE: To determine the feasibility of a randomised trial of ovarian cancer screening among women attending a breast cancer screening centre. DESIGN: Randomised controlled trial of ovarian cancer screening using transvaginal ultrasonography as a primary screening test and colour Doppler imaging as a secondary screening test in the screened group and no intervention in the control group. SETTING: Reading breast cancer screening centre (United Kingdom). SUBJECTS: 8678 women, without a bilateral oophorectomy or hysterectomy, aged between 50 and 64 attending for NHS breast cancer screening between September 1989 and February 1993. MAIN OUTCOME MEASURES: Uptake of ovarian cancer screening among eligible women and the screening false positive rate (considered as the referral rate to a gynaecologist for surgical intervention). RESULTS: 82% (7124/8678) of eligible women agreed to join the trial and were randomly allocated in equal numbers to each arm of the trial. 3280 women had an initial scan. The false positive rate after ultrasonography alone was 2.9% (86/2952), but this dropped to 0.5% after colour Doppler as a secondary screening test. One stage I primary ovarian cancer was detected at screening in a 58 year old women. CONCLUSIONS: A randomised trial of ovarian cancer screening using ultrasonography and colour Doppler imaging is feasible and acceptable among women attending a breast cancer screening centre. The results indicate that the expected odds of being affected given a positive result in the general population would be about 1:12. A full randomised trial of ovarian cancer screening with mortality as the end point is needed to assess whether screening reduces mortality from this disease. A multicentre European trial is currently in progress.

Costs and Cost Analysis↗
PubMed1994

European Society of Mastology Consensus Conference on breast cancer screening: report of the evaluation committee.

On 4 February 1993, the European Society of Mastology (EUSOMA) convened a meeting of experts in Paris to evaluate the current evidence on the value and hazards of breast cancer screening. The Committee consisted of individuals from different countries throughout Europe and from different disciplines. We summarise here the deliberations and conclusions of the Committee.

Adult↗
PubMed1994

First trimester biochemical screening for Down's syndrome.

A number of biochemical markers in maternal serum have been proposed for first trimester screening for Down's syndrome. The most promising four are pregnancy associated plasma protein A (PAPP-A), the free beta sub-unit of human chorionic gonadotrophin (hCG) (free beta glycoprotein sub-unit), unconjugated oestriol (uE3) and alpha-fetoprotein (AFP). An analysis of the published literature suggests that 70% of affected pregnancies could be detected for a 5% false-positive rate if the four markers are used in combination with maternal age and assumed to be independent measures of risk. This is a level of performance that is similar to second trimester screening. It is, however, a tentative estimate because of the assumption of independence and the possibility that the effect may be exaggerated by publication bias. Further research is needed before such screening is introduced. Other first trimester markers which have been studied include total hCG, free alpha-hCG, CA125, PLAP and SP1 but they either look unpromising or there are too few data available to determine their value. The timing of antenatal diagnosis by means of chorion villus sampling should be delayed until after 10 weeks of pregnancy because of the risk of causing limb defects. Screening need not, therefore, be performed before about 9 or 10 weeks of pregnancy.

Abortion, Induced↗