Red blood cell folate levels in Canadian Inuit women of childbearing years: influence of food security, body mass index, smoking, education, and vitamin use.

BACKGROUND: The benefits of folic acid for prevention of congenital anomalies are well known. For the Inuit of Canada, where vitamin use is low and access to folate-rich foods limited, fortification is likely a major source of intake. We sought to determine whether red blood cell folate (RBCF) levels of Inuit women reached accepted target levels. METHODS: The Inuit Health Survey, 2007-2008, included evaluation of RBCF levels among 249 randomly selected non-pregnant women of reproductive age. Using descriptive statistics and linear regression analyses, RBCF levels were assessed and compared across several socio-demographic variables to evaluate the characteristics associated with RBCF status. RESULTS: Mean (SD) RBCF levels of 935.5 nmol/L (± 192) reached proposed target levels (> 906 nmol/L); however, 47% of women had lower than target levels. In bivariate analysis, non-smoking, higher education, higher income, food security, increased body mass index, and vitamin use were each significantly associated with higher RBCF. Increased levels of smoking had a negative association with RBCF levels (- 5.8 nmol/L per cigarette smoked per day (p = 0.001)). A total of 6.8% of women reported taking vitamin supplements, resulting in a 226 nmol/L higher RBCF level on average compared to non-users (p < 0.001). CONCLUSION: While mean levels of folate reached target levels, this was largely driven by the small number of women taking vitamin supplements. Our results suggest that folate status is often too low in Inuit women of childbearing years. Initiatives to improve food security, culturally relevant education on folate-rich traditional foods, vitamin supplements, and smoking cessation/reduction programs may benefit Inuit women and improve birth outcomes.

Novel Variant in the ANK2 Membrane-Binding Domain Is Associated With Ankyrin-B Syndrome and Structural Heart Disease in a First Nations Population With a High Rate of Long QT Syndrome.

BACKGROUND: Long QT syndrome confers susceptibility to ventricular arrhythmia, predisposing to syncope, seizures, and sudden death. While rare globally, long QT syndrome is ≈15× more common in First Nations of Northern British Columbia largely because of a known mutation in KCNQ1. However, 2 large multigenerational families were affected, but negative for the known mutation. METHODS AND RESULTS: Long QT syndrome panel testing was carried out in the index case of each family, and clinical information was collected. Cascade genotyping was performed. Biochemical and myocyte-based assays were performed to evaluate the identified gene variant for loss-of-function activity. Index cases in these 2 families harbored a novel ANK2 c.1937C>T variant (p.S646F). An additional 16 carriers were identified, including 2 with structural heart disease: one with cardiomyopathy resulting in sudden death and the other with congenital heart disease. For all carriers of this variant, the average QTc was 475 ms (±40). Although ankyrin-B p.S646F is appropriately folded and expressed in bacteria, the mutant polypeptide displays reduced expression in cultured H9c2 cells and aberrant localization in primary cardiomyocytes. Furthermore, myocytes expressing ankyrin-B p.S646F lack normal membrane targeting of the ankyrin-binding partner, the Na/Ca exchanger. Thus, ankyrin-B p.S646F is a loss-of-function variant. CONCLUSIONS: We identify the first disease-causing ANK2 variant localized to the membrane-binding domain resulting in reduced ankyrin-B expression and abnormal localization. Further study is warranted on the potential association of this variant with structural heart disease given the role of ANK2 in targeting and stabilization of key structural and signaling molecules in cardiac cells.

Heavy smoking during pregnancy as a marker for other risk factors of adverse birth outcomes: a population-based study in British Columbia, Canada.

BACKGROUND: Smoking during pregnancy is associated with known adverse perinatal and obstetrical outcomes as well as with socio-economic, demographic and other behavioural risk factors that independently influence outcomes. Using a large population-based perinatal registry, we assess the quantity of cigarettes smoked for the magnitude of adverse birth outcomes and also the association of other socio-economic and behavioural risk factors documented within the registry that influence pregnancy outcomes. Our goal was to determine whether number of cigarettes smoked could identify those in greatest need for comprehensive intervention programs to improve outcomes. METHODS: Our population-based retrospective study of singleton births from 2001 to 2006 (N = 237,470) utilized data obtained from the BC Perinatal Database Registry. Smoking data, self reported at the earliest prenatal visit, was categorized as: never, former, light (1 to 4), moderate (5 to 9), or heavy smoker (10 or more per day). Crude and adjusted odds ratios (AOR) with 95% confidence intervals (95% CI) were calculated using logistic regression models for smoking frequency and adverse birth outcomes. A partial proportional odds (pp-odds) model was used to determine the association between smoking status and other risk factors. RESULTS: There were 233,891 singleton births with available smoking status data. A significant dose-dependent increase in risk was observed for the adverse birth outcomes small-for-gestational age, term low birth weight and intra-uterine growth restriction. Results from the pp-odds model indicate heavy smokers were more likely to have not graduated high school: AOR (95% CI) = 3.80 (3.41-4.25); be a single parent: 2.27 (2.14-2.42); have indication of drug or alcohol use: 7.65 (6.99-8.39) and 2.20 (1.88-2.59) respectively, attend fewer than 4 prenatal care visits: 1.39 (1.23-1.58), and be multiparous: 1.59 (1.51-1.68) compared to light, moderate and non-smokers combined. CONCLUSION: Our data suggests that self reports of heavy smoking early in pregnancy could be used as a marker for lifestyle risk factors that in combination with smoking influence birth outcomes. This information may be used for planning targeted intervention programs for not only smoking cessation, but potentially other support services such as nutrition and healthy pregnancy education.

Maternal smoking at first prenatal visit as a marker of risk for adverse pregnancy outcomes in the Qikiqtaaluk (Baffin) Region.

INTRODUCTION: In Nunavut, 60-80% of pregnant women report smoking in pregnancy, a rate five times the Canadian average. Nunavut also has the highest rates of preterm birth and low birth weight infants in Canada. The present study assessed whether the number of cigarettes smoked per day, as recorded in the first trimester, influenced birth outcomes. METHODS: Maternal-newborn charts were reviewed for infants born between 1 January 2003 and 31 December 2005 to at least one Inuit parent in the Qikiqtaaluk (Baffin) region of Nunavut. Smoking data, as reported by the mother at an early prenatal visit, were extracted from the prenatal record. Birth outcomes including birth weights (for term births), low birth weight, small for gestational age births and rates of preterm birth, were analysed according to category of reported number of cigarettes smoked (0, 1-5, 6-10, and >10 per day). Maternal age, alcohol and street drug use were also assessed for each category of smokers. Statistical analysis among groups was carried out. RESULTS: Of 918 births meeting the study criteria, more than 80% of women reported smoking. For 80% of those, the amount smoked per day was available. Non-smokers and women smoking less than 5 cigarettes daily had perinatal outcomes equal to or better than Canadian averages for low birth weight, small for gestational age, and preterm birth. Furthermore, average birth weights at term significantly decreased from 3681 g for non smokers to 3310 g for those smoking more than 10 cigarettes per day. Compared with non-smokers, women in the highest smoking category (>10 cigarettes daily) had a six-fold increase in low birth weight infants (OR 6.7, 95% CI 2.3-19.6), almost a four-fold increase for small for gestational age births (OR 3.7, 95% CI 1.6-8.8) and twice the chance of a premature birth compared with non-smokers (OR 2.14, 95% CI 1.1-4.2). Those in the highest smoking category were also most likely to report alcohol and other substance use. CONCLUSIONS: Inuit women who reported not smoking, or smoking less than 5 cigarettes per day had birth outcomes equal or superior to average Canadian outcomes in each category evaluated. Those women reporting smoking more than 10 cigarettes daily had significantly increased risk for preterm birth, low birth weight and small for gestational age infants. Because those in the highest smoking category also reported the highest rates of alcohol and other substance use, it is likely that a combination of factors assessed in this study influenced the outcomes. Along with public health preventative measures to reduce smoking directed to this high risk group, other contributing factors for adverse birth outcomes need to be assessed more fully to understand the complex interactions that lead to increased smoking, substance use and, therefore, adverse birth outcomes. Furthermore, evidence from this study suggests that smoking more than 10 cigarettes per day, reported at first prenatal visit, may provide a marker for those women at highest risk of poor outcomes, which could provide direction for focused public health efforts.