A search for factors associated with reduced carbohydrate intake and NTD risk in two population-based studies.

BACKGROUND: Two population-based case-control studies have reported an increased risk of neural tube defect (NTD)-affected pregnancies among women with low carbohydrate diet in the periconceptional period. Given that only two studies have investigated this association, it is unclear to what degree the findings could be impacted by residual confounding. Here, we further interrogated both studies that observed this association with the objective to identify factors from a much larger number of factors that might explain the association. METHODS: By employing a machine learning algorithm (random forest), we investigated a baseline set of over 200 variables. These analyses produced the top 10 variables in each data set for cases and controls that predicted periconceptional low carbohydrate intake. RESULTS: Examining those prediction variables with logistic regression modeling, we did not observe any particular variable that substantially contributed to the NTD-low carbohydrate association in either data set. CONCLUSIONS: If there are underlying factors that explain the association, our findings suggest that none of the 200+ variables we examined were sufficiently correlated with what that true explanatory exposure may be. Alternatively, our findings may suggest that there are other unidentified factor(s) at play, or the association observed in two independent data sets is directly related to low carbohydrate intake.

An application of data mining to identify potential risk factors for anophthalmia and microphthalmia.

BACKGROUND: We examined a large number of variables to generate new hypotheses regarding a wider range of risk factors for anophthalmia/microphthalmia using data mining. METHODS: Data were from the National Birth Defects Prevention Study, a multicentre, case-control study from 10 centres in the United States. There were 134 cases of "isolated" and 87 "nonisolated" (with other major birth defects) of anophthalmia/microphthalmia and 11 052 nonmalformed controls with delivery dates October 1997-December 2011. Using random forest, a data mining procedure, we compared the two case types with controls for 201 variables. Variables considered important ranked by random forest were included in a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals. RESULTS: Predictors for isolated cases included paternal race/ethnicity, maternal intake of certain nutrients and foods, and childhood health problems in relatives. Using regression, inverse associations were observed with greater maternal education and with increasing intake of folate and potatoes. Odds were slightly higher with greater paternal education, for increased intake of carbohydrates and beans, and if relatives had a childhood health problem. For nonisolated cases, predictors included paternal race/ethnicity, maternal intake of certain nutrients, and smoking in the home the month before conception. Odds were higher for Hispanic fathers and smoking in the home and NSAID use the month before conception. CONCLUSIONS: Results appear to support previously hypothesised risk factors, socio-economic status, NSAID use, and inadequate folate intake, and potentially provide new areas such as passive smoking pre-pregnancy, and paternal education and ethnicity, to explore for further understanding of anophthalmia/microphthalmia.

Racial differences in maternal and umbilical cord blood leukocyte telomere length and their correlations.

PURPOSE: Telomere length at birth sets the baseline for telomere shortening and may influence adult disease risk like cancer. Telomere length is heritable, but may also be a marker of exposures in utero, including those influencing racial differences in risk. We examined racial differences in telomere length in maternal and umbilical cord blood from male neonates, and maternal-neonate correlations to generate hypotheses. METHODS: Black and white pregnant women were recruited in 2006-2007 and followed to postpartum. Data came from questionnaires and medical records. Relative telomere length was measured by qPCR in leukocyte DNA. We estimated mean telomere length in mothers and neonates (n = 55 pairs) using linear regression and maternal-cord blood Spearman correlations, overall and by race. RESULTS: Black mothers had shorter age- and plate-adjusted telomere length (2.49, 95% CI 2.11-2.86) than whites (2.92, 95% CI 2.63-3.22; p = 0.1) and black neonates had shorter telomere length (2.58, 95% CI 2.16-3.01) than whites (3.13, 95% CI 2.79-3.47; p = 0.1), though not statistically significant. Differences were attenuated after further adjustment for maternal factors. Maternal-cord blood correlations were moderate (r = 0.53, p < 0.0001), and did not differ by race. CONCLUSION: Telomere length may differ by race at birth due to both inherited and racial differences in maternal factors. This study was for hypothesis generation and results should be followed up in larger studies.

Influence of In Utero Maternal and Neonate Factors on Cord Blood Leukocyte Telomere Length: Clues to the Racial Disparity in Prostate Cancer?

Background. Modifiable factors in adulthood that explain the racial disparity in prostate cancer have not been identified. Because racial differences in utero that may account for this disparity are understudied, we investigated the association of maternal and neonate factors with cord blood telomere length, as a cumulative marker of cell proliferation and oxidative damage, by race. Further, we evaluated whether cord blood telomere length differs by race. Methods. We measured venous umbilical cord blood leukocyte relative telomere length by qPCR in 38 black and 38 white full-term male neonates. Using linear regression, we estimated geometric mean relative telomere length and tested for differences by race. Results. Black mothers were younger and had higher parity and black neonates had lower birth and placental weights. These factors were not associated with relative telomere length, even after adjusting for or stratifying by race. Relative telomere length in black (2.72) and white (2.73) neonates did not differ, even after adjusting for maternal or neonate factors (all p > 0.9). Conclusions. Maternal and neonate factors were not associated with cord blood telomere length, and telomere length did not differ by race. These findings suggest that telomere length at birth does not explain the prostate cancer racial disparity.