Evidence-based, cost-effective interventions: how many newborn babies can we save?

Food and Agricultural Organization of the United Nations PA N I S F I A T G u id e in e s o n fo o d fo r tific atio n w th m ic r o n u tr ie n ts Interest in micronutrient malnutrition has increased greatly over the last few years. One of the main reasons is the realization that micronutrient malnutrition contributes substantially to the global burden of disease. Furthermore, although micronutrient malnutrition is more frequent and severe in the developing world and among disadvantaged populations, it also represents a public health problem in some industrialized countries. Measures to correct micronutrient deficiencies aim at ensuring consumption of a balanced diet that is adequate in every nutrient. Unfortunately, this is far from being achieved everywhere since it requires universal access to adequate food and appropriate dietary habits. Food fortification has the dual advantage of being able to deliver nutrients to large segments of the population without requiring radical changes in food consumption patterns.

Guidelines on food fortification with micronutrients

Physical environment, man-made pollution, nutrition and their mutual interactions can be major causes of human diseases. These disease determinants have distinct spatial distributions across geographical units, so that their adequate study involves the investigation of the associated geographical strata. We propose four geographical detectors based on spatial variation analysis of the geographical strata to assess the environmental risks of health: the risk detector indicates where the risk areas are; the factor detector identifies factors that are responsible for the risk; the ecological detector discloses relative importance between the factors; and the interaction detector reveals whether the risk factors interact or lead to disease independently. In a real-world study, the primary physical environment (watershed, lithozone and soil) was found to strongly control the neural tube defects (NTD) occurrences in the Heshun region (China). Basic nutrition (food) was found to be more important than man-made pollution (chemical fertilizer) in the control of the spatial NTD pattern. Ancient materials released from geological faults and subsequently spread along slopes dramatically increase the NTD risk. These findings constitute valuable input to disease intervention strategies in the region of interest.

/pdf/geographical-detectors-based-health-risk-assessment-and-its-2kb4fe64zr.pdf

Geographical Detectors-Based Health Risk Assessment and its Application in the Neural Tube Defects Study of the Heshun Region, China

Common strategies to decide whether a variable is a confounder that should be adjusted for in the analysis rely mostly on statistical criteria. The authors present findings from the Slone Epidemiology Unit Birth Defects Study, 1992-1997, a case-control study on folic acid supplementation and risk of neural tube defects. When statistical strategies for confounding evaluation are used, the adjusted odds ratio is 0.80 (95% confidence interval: 0.62, 1.21). However, the consideration of a priori causal knowledge suggests that the crude odds ratio of 0.65 (95% confidence interval: 0.46, 0.94) should be used because the adjusted odds ratio is invalid. Causal diagrams are used to encode qualitative a priori subject matter knowledge.

http://www.faculty.umb.edu/pjt/epi/hernan02.pdf

Causal Knowledge as a Prerequisite for Confounding Evaluation: An Application to Birth Defects Epidemiology

Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.

/pdf/facts-and-recommendations-about-total-homocysteine-23jbkelsns.pdf

Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

Background Periconceptional use of multivitamins containing folic acid can reduce a woman's risk of having a baby with a neural-tube defect. Methods As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 μg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Results Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the nort...

https://www.nejm.org/doi/pdf/10.1056/NEJM199911113412001

Prevention of Neural-Tube Defects with Folic Acid in China

BACKGROUND AND METHODS\nPericonceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy.\n\n\nRESULTS\nAmong the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent).\n\n\nCONCLUSIONS\nPericonceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

Prevention of Neural-Tube Defects With Folic Acid in China

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(03)12390-2.pdf

Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study.

Evaluation of the informed consent process in a randomized controlled trial in China: the Sino-U.S. NTD project.

Objective To describe and analyze epidemiological characteristics of babies with neural tube defects (NTD) by sex and birth outcome in a high-prevalence and a low-prevalence areas of China. Methods Birth defects surveillance data collected from 1992 through 1994, as a part of the Sino-American cooperative project on NTD prevention, were used to classify NTD as four categories, i.e., anencephaly, encephalocele, high-level and low-level spina bifida according to the sites of lesion (high vs. low level lesion were cervicothoracic and lumbosacral, respectively). Each category was sub-classified, according to single or compound defect, as isolated external defects (including those with NTD only) or multiple external defects (including those with NTD and another major external birth defects that is not the sequence of a defect such as cleft lip with or without cleft palate). The rates of anencephalus, encephalocele, high- and low-level spina bifida (SB) in males and females and their sex ratios were calculated, adjusted for urban and rural areas, season, category and birth outcome by sex and sites of lesions (high vs. low). Results Totally, 784 NTD cases were identified from 326 874 recorded births (including live births, stillbirths and fetal deaths with a gestation age of at least 20 weeks). The prevalence rates of anencephalus (1.30 per 1 000 female births) and high-level SB (3.99) in females were higher than those (0.66 and 1.66 per 1 000 male births) in males in the high-prevalence northern regions; with adjusted prevalence rates of females 1.8 - 2.1 times greater than those of males. In the low-prevalence southern regions, the prevalence of high- (0.32 per 1 000 female births) and low-level SB (0.21) in female were higher than those in males, with high- and low-level SB rate of 0.10 and 0.09 per 1 000 male births), with adjusted rates for females of 1.3 - 1.6 times higher than in males. Isolated NTD accounted for more than 80% of all NTD cases, and the prevalence of isolated NTD in females (2.57) was higher than that in males (1.40). Conclusions The sex differences in NTD existed between north and south, in accordance with the phenotype of NTD. It suggested that proportion of high level SB and anencephalus in females could increase as the prevalence of NTD going up, anencephaly, high- and low-level SB had the different genetic and environmental background.

Hong Wang

Papers

Prevention of Neural-Tube Defects with Folic Acid in China

Prevention of Neural-Tube Defects With Folic Acid in China

Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study.

Evaluation of the informed consent process in a randomized controlled trial in China: the Sino-U.S. NTD project.

[Sex distribution of neural tube defects and their birth outcome in high- and low-prevalence areas of China].