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N J Wald

Publications and source records attributed to N J Wald.

At least 37 records · Page 2Linked to original sources
PubMed2001

Quantifying the effect of folic acid.

BACKGROUND: Folic acid is known to prevent neural-tube defects (NTDs) but the size of the effect for a given dose is unclear. We aimed to quantify such an effect. METHODS: We used published data from 13 studies of folic acid supplementation on serum folate concentrations and results from a large cohort study of the risk of NTDs according to serum folate, to measure the preventive effect of specified increases in intake of folic acid. FINDINGS: Serum folate concentrations increase by 0.94 ng/mL (95% CI 0.77-1.10) for every 0.1 mg/day increase in folic acid intake in women aged 20-35 years, and about double that in people aged 40-65. Every doubling of serum folate concentration roughly halves the risk of an NTD. These two effects can be combined to predict the reduction in risk according to intake of extra folic acid and background serum folate concentration. Such results predict that the preventive effect is greater in women with low serum folate than in those with higher concentrations. The results have also been used to predict direct observations from large randomised trials and the effect of food fortification. From a typical western background serum folate of 5 ng/mL, about 0.2 mg/day (the US level of folic acid fortification) would be expected to reduce NTDs by about 20%; a similar effect can be expected from the current British recommendation (0.24 mg/day). An increase of 0.4 mg/day would reduce risk by about 36%, of 1 mg/day by 57%, and taking a 5-mg tablet daily would reduce risk by about 85%. INTERPRETATION: Folic acid fortification levels should be increased. Additionally women planning a pregnancy should take 5 mg folic acid tablets daily, instead of the 0.4 mg dose presently recommended.

Adult↗
PubMed2001

Randomized trial of folic acid supplementation and serum homocysteine levels.

BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Adult↗
PubMed2001

Assessment of the value of reporting partial screening results in prenatal screening for Down syndrome.

Prenatal screening for Down syndrome can be performed using the first trimester Combined Test [nuchal translucency (NT), pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin (hCG) and maternal age] or the Integrated Test (for example, NT and PAPP-A in the first trimester and two or more serum markers in the second trimester, all with maternal age). We investigated the value of providing partial results when using the Combined Test or Integrated Test to identify women with a high enough risk of having an affected pregnancy based on NT and maternal age alone such that there would be little advantage in combining this information with data on the serum markers. We also assessed whether in programmes using the Integrated Test it is worthwhile reporting partial results based on risk using first trimester markers and not obtaining a second trimester blood sample. Published data based on 480 affected and 96 839 unaffected pregnancies were used for the present study. Using NT and age alone, about 0.14% of all women screened would have such a high risk that they would always remain screen-positive after the Combined Test and only 0.06% would remain screen-positive after the Integrated Test. Similarly, about 0.07% of all women screened who have a high risk based on NT, PAPP-A and age would remain screen-positive after the Integrated Test. These percentages are too small to justify reporting two risk estimates for all women, given the confusion this would generate. It is therefore not worthwhile reporting partial risk estimates in screening programmes using the Combined Test or Integrated Test.

Adult↗
PubMed2001

Multiple marker second trimester serum screening for pre-eclampsia.

OBJECTIVE: To investigate whether an appropriate combination of maternal serum inhibin A, free beta-human chorionic gonadotropin (free beta-hCG), unconjugated estriol (uE3), and alpha-fetoprotein (AFP) may be an effective means of screening for pre-eclampsia in the second trimester of pregnancy. SETTING: Women who attended an antenatal clinic in Oxford, from whom serum samples were stored, 19 of whom subsequently developed pre-eclampsia. METHODS: Serum inhibin A, free beta-hCG, uE3, and AFP were measured in 32 serum samples collected from the 19 women who developed pre-eclampsia and, for each sample, in three control samples collected from women with unaffected pregnancies matched for gestational age and maternal age. RESULTS: In pregnancies that developed pre-eclampsia the median inhibin A value was raised (1.7 multiples of the median (MoM) for unaffected pregnancies (95% confidence interval (95% CI) 1.1 to 2.7 MoM), the median free beta-hCG was raised (2.1, 1.4 to 3.3 MoM) and the median uE3 was lowered (0.8, 0.6 to 0.98 MoM) after 19 completed weeks of gestation and at least 2 weeks before the onset ofproteinuria. Values of AFP were similar in affected and unaffected pregnancies. Combining the values ofinhibin A, free beta-hCG, and uE3 to form a screening test would detect an estimated 55% of affected pregnancies with a false positive rate of 5%. CONCLUSIONS: Inhibin A, free beta-hCG, and uE3 in combination may be a useful screening test during the second trimester for pre-eclampsia.

Biomarkers↗