1. Red blood cell (RBC) folate concentration from maternal serum was used to predict the incidence of neural tube defects in a population and to assess the impact of folic acid food fortification programs.
2. The greatest reduction in risk of neural tube defects was achieved when a woman’s RBC folate concentration during pregnancy is between 1000-1300 nmol/L.
Evidence Rating Level: 2 (Good)
Study Rundown: Multiple studies have shown that increased maternal folic acid intake before and during pregnancy reduces the risk of neural tube defects. Unfortunately, it is difficult to estimate fetal exposure to folic acid using recall of maternal dietary intake or using plasma folate levels, which are only short-term measures of blood folate concentration. This study aimed to substantiate a more reliable measure of folic acid intake, red blood cell (RBC) folate concentration, and determine an optimal level to reduce the risk of neural tube defects. The authors applied a Bayesian model to data from two Chinese population-based studies in which women received folic acid supplementation before and during pregnancy. They found an inverse dose-response relationship between RBC folate concentration and risk of neural tube defects. They also determined that RBC folate concentration between 1000-1300 nmol/L achieves optimal prevention of neural tube defects.
The study boasts a large sample size, results consistent with those observed by in a previous study of Irish women, and the ability to accurately model the prevalence of neural tube defects in the US population before and after mandatory folic acid fortification. However, a limitation is that maternal RBC folate concentration for one of the Chinese studies was estimated based on reported pill consumption instead of actual measurements. This study adds to the literature by confirming that RBC folate concentration is directly related to rates of neural tube defects, and that an optimal threshold for RBC folate concentration (1000 nmol/L) can be used a biomarker to develop and monitor population-based folic acid fortification programs.
Relevant Reading: Folate levels and neural tube defects: implications for prevention
In-Depth [outcomes analysis]: The authors used data on folic acid intake and neural tube defects from two Chinese population based studies in which women received folic acid supplementation before and during pregnancy to establish a quantitative relationship between RBC folate concentration and risk of neural tube defects. The first Chinese study was a community intervention project in 1993-95 in which 247, 831 Chinese women received 400 micrograms of folic acid supplementation daily before and during their early pregnancy. The second study was a randomized clinical trial of folic acid supplementation in 2003-05 in which 1,194 Chinese women were assigned to different dosages of folic acid (100-4000μg/day). Red blood cell folate concentration data from the randomized clinical trial was used to estimate RBC folate concentration levels for participants in the first trial based on their reported pill consumption. A Bayesian model was applied and a dose-response relationship between RBC folate concentration and risk of neural tube defects was found. Specifically, compared to 25.4 neural tube defects per 10,000 births at an RBC folate concentration of 500 nmol/L, there were only 6 neural tube defects per 10,000 births at RBC folate concentrations above 1,000 nmol/L. RBC folate concentration between 1000-1300 nmol/L achieved optimal prevention of neural tube defects. The authors applied the model to the United States population using published RBC folate distributions before and after folic acid fortification and were able to accurately model the prevalence of neural tube defects.
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