The roles of IGF2 and DNMT methylation and elongase6 related fatty acids in metabolic syndrome.

Background: The prevalence of metabolic syndrome (MetS) has increased along with rapid socio-economic development in China in recent decades, aggravating the burden of the health care system. Both plasma levels of fatty acids (FAs) and aberrant DNA methylation profiles are associated with MetS risk. However, studies exploring the role of DNA methylation and FAs simultaneously in MetS etiology are sparse. Objective: We aimed to explore the association between the gene methylation levels of insulin-like growth factor II (IGF2), H19, DNA methyltransferases 1 (DNMT1), DNA methyltransferases 3a (DNMT3a), and DNA methyltransferases 3b (DNMT3b) and MetS risk, and the etiological role of elongation of very-long-chain fatty acid elongase 6 (ELOVL6) related fatty acids. Method: Plasma levels of FAs were measured using a Gas Chromatography-Flame Ionization Detector (GC-FID) after organic extraction, and gene methylation was quantified using a real-time Quantitative Polymerase Chain Reaction (Q-PCR) detecting system after bisulfite treatment. The C18/C16 ratio was used as the indicator of ELOVL6 activity. Odds Ratio (OR) and 95% Confidence Interval (CI) were estimated with logistic regression. Results: Methylation levels in IGF2 and DNMT3a were not significantly associated with MetS risk. However, when stratified by C18/C16 ratio (high vs. low), positive associations were observed between the risk of MetS and methylation levels (>median) of IGF2a3 (OR = 3.1, 95% CI = 1.3-7.5) and DNMT3a (OR = 2.5, 95% CI = 1.1-5.8) genes, in individuals with lower C18/C16 ratios, while no significant associations were observed in subjects with high C18/C16 ratios. Conclusion: Methylation levels in IGF2 and DNMT3a genes may affect the risk of MetS in an ELOVL6 activity-dependent way among Chinese adults. Further studies in other populations are needed to validate this finding.

Disparities and Trends in Birth Outcomes, Perinatal and Infant Mortality in Aboriginal vs. Non-Aboriginal Populations: A Population-Based Study in Quebec, Canada 1996-2010.

BACKGROUND: Aboriginal populations are at substantially higher risks of adverse birth outcomes, perinatal and infant mortality than their non-Aboriginal counterparts even in developed countries including Australia, U.S. and Canada. There is a lack of data on recent trends in Canada. METHODS: We conducted a population-based retrospective cohort study (n = 254,410) using the linked vital events registry databases for singleton births in Quebec 1996-2010. Aboriginal (First Nations, Inuit) births were identified by mother tongue, place of residence and Indian Registration System membership. Outcomes included preterm birth, small-for-gestational-age, large-for-gestational-age, low birth weight, high birth weight, stillbirth, neonatal death, postneonatal death, perinatal death and infant death. RESULTS: Perinatal and infant mortality rates were 1.47 and 1.80 times higher in First Nations (10.1 and 7.3 per 1000, respectively), and 2.37 and 4.46 times higher in Inuit (16.3 and 18.1 per 1000, respectively) relative to non-Aboriginal (6.9 and 4.1 per 1000, respectively) births (all p<0.001). Compared to non-Aboriginal births, preterm birth rates were persistently (1.7-1.8 times) higher in Inuit, large-for-gestational-age birth rates were persistently (2.7-3.0 times) higher in First Nations births over the study period. Between 1996-2000 and 2006-2010, as compared to non-Aboriginal infants, the relative risk disparities increased for infant mortality (from 4.10 to 5.19 times) in Inuit, and for postneonatal mortality in Inuit (from 6.97 to 12.33 times) or First Nations (from 3.76 to 4.25 times) infants. Adjusting for maternal characteristics (age, marital status, parity, education and rural vs. urban residence) attenuated the risk differences, but significantly elevated risks remained in both Inuit and First Nations births for the risks of perinatal mortality (1.70 and 1.28 times, respectively), infant mortality (3.66 and 1.47 times, respectively) and postneonatal mortality (6.01 and 2.28 times, respectively) in Inuit and First Nations infants (all p<0.001). CONCLUSIONS: Aboriginal vs. non-Aboriginal disparities in adverse birth outcomes, perinatal and infant mortality are persistent or worsening over the recent decade in Quebec, strongly suggesting the needs for interventions to improve perinatal and infant health in Aboriginal populations, and for monitoring the trends in other regions in Canada.

Health-related quality of life and health service utilization in Chinese rural-to-urban migrant workers.

OBJECTIVES: The number of rural-to-urban migrant workers has been increasing rapidly in China over recent decades, but there is a scarcity of data on health-related quality of life (HRQOL) and health service utilization among Chinese rural-to-urban migrant workers in comparison to local urban residents. We aimed to address this question. METHODS: This was a cross-sectional study of 2315 rural-to-urban migrant workers and 2347 local urban residents in the Shenzhen-Dongguan economic zone (China) in 2013. Outcomes included HRQOL (measured by Health Survey Short Form 36) and health service utilization (self-reported). RESULTS: Compared to local urban residents, rural-to-urban migrant workers had lower scores in all domains of HRQOL, and were more likely to report chronic illnesses (9.2% vs. 6.0%, adjusted OR = 1.62, 95% CI 1.28-2.04) and recent two-week morbidity (21.3% vs. 5.0%, adjusted OR = 5.41, 95% CI 4.26-6.88). Among individuals who reported sickness in the recent two weeks, migrant workers were much less likely to see a doctor (32.7% vs. 66.7%, adjusted OR = 0.21, 95% CI 0.13-0.36). CONCLUSIONS: Chinese rural-to-urban migrant workers have lower HRQOL, much more frequent morbidity, but are also much less likely to see a doctor in times of sickness as compared to local urban residents, indicating the existence of significant unmet medical care needs in this population.

Widening inequality in extreme macrosomia between Indigenous and non-Indigenous populations of Québec, Canada.

OBJECTIVE: To evaluate trends in macrosomia by severity in Indigenous vs. non-Indigenous populations of Québec, Canada. METHODS: We used a retrospective cohort of 2,298,332 singleton live births in the province of Québec, 1981-2008. Indigenous births were identified by community of residence (First Nations, Inuit, non-Indigenous) and language spoken (First Nations, Inuit, French/English). High birth weight (HBW) and large-for-gestational-age (LGA) births were categorised by severity (moderate, very, extreme). Time trends in HBW and LGA, by severity, were estimated using odds ratios (OR) and rate differences for Indigenous vs. non-Indigenous births, adjusting for maternal characteristics. RESULTS: Relative to non-Indigenous, First Nations (but not Inuit) had higher rates of extreme HBW (1.3% vs. 0.1%) and extreme LGA birth (12.6% vs. 2.2%), and rates increased over time. First Nations had progressively elevated ORs with greater severity of macrosomia, and associations were strongest for extreme HBW >5,000 g (OR=12.4) and LGA >97th percentile (OR=7.2). CONCLUSION: Inequalities in extreme macrosomia between First Nations and non-Indigenous Quebecers are pronounced and widened between 1981 and 2008. IMPLICATIONS: Studies are needed to determine why macrosomia rates are increasing in Québec's First Nations, and how they compare with Indigenous sub-groups of demographically similar countries, including Australia and New Zealand.

Birth outcomes in the Inuit-inhabited areas of Canada.

BACKGROUND: Information on health disparities between Aboriginal and non-Aboriginal populations is essential for developing public health programs aimed at reducing such disparities. The lack of data on disparities in birth outcomes between Inuit and non-Inuit populations in Canada prompted us to compare birth outcomes in Inuit-inhabited areas with those in the rest of the country and in other rural and northern areas of Canada. METHODS: We conducted a cohort study of all births in Canada during 1990-2000 using linked vital data. We identified 13,642 births to residents of Inuit-inhabited areas and 4,054,489 births to residents of all other areas. The primary outcome measures were preterm birth, stillbirth and infant death. RESULTS: Compared with the rest of Canada, Inuit-inhabited areas had substantially higher rates of preterm birth (risk ratio [RR] 1.45, 95% confidence interval [CI] 1.38-1.52), stillbirth (RR 1.68, 95% CI 1.38-2.04) and infant death (RR 3.61, 95% CI 3.17-4.12). The risk ratios and absolute differences in risk for these outcomes changed little over time. Excess mortality was observed for all major causes of infant death, including congenital anomalies (RR 1.64), immaturity-related conditions (RR 2.96), asphyxia (RR 2.43), sudden infant death syndrome (RR 7.15), infection (RR 8.32) and external causes (RR 7.30). Maternal characteristics accounted for only a small part of the risk disparities. Substantial risk ratios for preterm birth, stillbirth and infant death remained when the comparisons were restricted to other rural or northern areas of Canada. INTERPRETATION: The Inuit-inhabited areas had much higher rates of preterm birth, stillbirth and infant death compared with the rest of Canada and with other rural and northern areas. There is an urgent need for more effective interventions to improve maternal and infant health in Inuit-inhabited areas.

Individual- and Community-Level Disparities in Birth Outcomes and Infant Mortality among First Nations, Inuit and Other Populations in Quebec.

OBJECTIVE: We assessed individual- and community-level disparities and trends in birth outcomes and infant mortality among First Nations (North American Indians) and Inuit versus other populations in Quebec, Canada. METHODS: A retrospective birth cohort study of all births to Quebec residents, 1991-2000. At the individual level, we examined outcomes comparing births to First Nations and Inuit versus other mother tongue women. At the community level, we compared outcomes among First Nations and Inuit communities versus other communities. RESULTS: First Nations and Inuit births were much less likely to be small-for-gestational-age but much more likely to be large-for-gestational-age compared to other births at the individual or community level, especially for First Nations. At both levels, Inuit births were 1.5 times as likely to be preterm. At the individual level, total fetal and infant mortality rates were 2 times as high for First Nations, and 3 times as high for Inuit. Infant mortality rates were 2 times as high for First Nations, and 4 times as high for Inuit. There were no reductions in these disparities between 1991-1995 and 1996-2000. Modestly smaller disparities in total fetal and infant mortality were observed for First Nations at the community level (risk ratio=1.6), but for Inuit there were similar disparities at both levels. These disparities remained substantial after adjusting for maternal characteristics. CONCLUSION: There were large and persistent disparities in fetal and infant mortality among First Nations and Inuit versus other populations in Quebec based on individual- or community-level assessments, indicating a need to improve socioeconomic conditions as well as perinatal and infant care for Aboriginal peoples.

Large prospective birth cohort studies on environmental contaminants and child health - goals, challenges, limitations and needs.

The adverse health effects of environmental contaminants (ECs) are a rising public health concern, and a major threat to sustainable socioeconomic development. The developing fetuses and growing children are particularly vulnerable to the adverse effects of ECs. However, assessing the health impact of ECs presents a major challenge, given that multiple outcomes may arise from one exposure, multiple exposures may result in one outcome, and the complex interactions between ECs, and between ECs, nutrients and genetic factors, and the dynamic temporal changes in EC exposures during the life course. Large-scale prospective birth cohort studies collecting extensive data and specimen starting from the prenatal or pre-conception period, although costly, hold promise as a means to more clearly quantify the health effects of ECs, and to unravel the complex interactions between ECs, nutrients and genotypes. A number of such large-scale studies have been launched in some developed counties. We present an overview of "why", "what" and "how" behind these efforts with an objective to uncover major unidentified limitations and needs. Three major limitations were identified: (1) limited data and bio-specimens regarding early life EC exposure assessments in some birth cohort studies; (2) heavy participant burdens in some birth cohort studies may bias participant recruitment, and risk substantial loss to follow-up, protocol deviations limiting the quality of data and specimens collection, with an overall potential bias towards the null effect; (3) lack of concerted efforts in building comparable birth cohorts across countries to take advantage of natural "experiments" (large EC exposure level differences between countries) for more in-depth assessments of dose-response relationships, threshold exposure levels, and positive and negative effect modifiers. Addressing these concerns in current or future large-scale birth cohort studies may help to produce better evidence on the health effects of ECs.

The joint influence of marital status, interpregnancy interval, and neighborhood on small for gestational age birth: a retrospective cohort study.

BACKGROUND: Interpregnancy interval (IPI), marital status, and neighborhood are independently associated with birth outcomes. The joint contribution of these exposures has not been evaluated. We tested for effect modification between IPI and marriage, controlling for neighborhood. METHODS: We analyzed a cohort of 98,330 live births in Montréal, Canada from 1997-2001 to assess IPI and marital status in relation to small for gestational age (SGA) birth. Births were categorized as subsequent-born with short (<12 months), intermediate (12-35 months), or long (36+ months) IPI, or as firstborn. The data had a 2-level hierarchical structure, with births nested in 49 neighborhoods. We used multilevel logistic regression to obtain adjusted effect estimates. RESULTS: Marital status modified the association between IPI and SGA birth. Being unmarried relative to married was associated with SGA birth for all IPI categories, particularly for subsequent births with short (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.31-1.95) and intermediate (OR 1.48, 95% CI 1.26-1.74) IPIs. Subsequent births had a lower likelihood of SGA birth than firstborns. Intermediate IPIs were more protective for married (OR 0.50, 95% CI 0.47-0.54) than unmarried mothers (OR 0.65, 95% CI 0.56-0.76). CONCLUSION: Being unmarried increases the likelihood of SGA birth as the IPI shortens, and the protective effect of intermediate IPIs is reduced in unmarried mothers. Marital status should be considered in recommending particular IPIs as an intervention to improve birth outcomes.

Effect of neighbourhood income and maternal education on birth outcomes: a population-based study.

BACKGROUND: Maternal socioeconomic status (SES) is an important determinant of inequity in maternal and fetal health. We sought to determine the extent to which associations between adverse birth outcomes and SES can be identified using individual-level measures (maternal level of education) and community-level measures (neighbourhood income). METHODS: In Quebec, the birth registration form includes a field for the mother's years of education. Using data from birth registration certificates, we identified all births from 1991 to 2000. Using maternal postal codes that can be linked to census enumeration areas, we determined neighbourhood income levels that reflect SES. RESULTS: Lower levels of both maternal education and neighbourhood income were associated with elevated crude risks of preterm birth, small-for-gestational-age (SGA) birth, stillbirth and neonatal and postneonatal death. The effects of maternal education were stronger than, and independent of, those of neighbourhood income. Compared with women in the highest neighbourhood income quintile, women in the lowest quintile were significantly more likely to have a preterm birth (adjusted odds ratio [OR] 1.14, 95% confidence interval [CI] 1.10-1.17), SGA birth (OR 1.18, 95% CI 1.15-1.21) or stillbirth (OR 1.30, 95% CI 1.13-1.48); compared with mothers who had completed community college or at least some university, mothers who had not completed high school were significantly more likely to have a preterm birth (adjusted OR 1.48, 95% CI 1.44-1.52), SGA birth (OR 1.86, 95% CI 1.82-1.91) or stillbirth (OR 1.54, 95% CI 1.36-1.74). INTERPRETATION: Individual and, to a lesser extent, neighbourhood-level SES measures are independent indicators for subpopulations at risk of adverse birth outcomes. Women with lower education levels and those living in poorer neighbourhoods are more vulnerable to adverse birth outcomes and may benefit from heightened clinical vigilance and counselling.

Disparities in birth outcomes by neighborhood income: temporal trends in rural and urban areas, british columbia.

BACKGROUND: Knowledge of socioeconomic disparities in health is of interest to both the general public and public health policymakers. It is unclear how disparities in birth outcomes by socioeconomic status have changed over time, particularly in settings with universal health insurance and favorable socioeconomic conditions. METHODS: We identified a cohort of all births (n = 713,950) registered in British Columbia, 1985-2000. We compared rates and relative risks (RRs) of preterm birth, small-for-gestational-age (SGA), stillbirth, and neonatal and postneonatal death across neighborhood-income quintiles from Q1 (richest, the reference) to Q5 (poorest) by 4-year intervals in rural and urban areas. Logistic regression was used to control for maternal and pregnancy characteristics. RESULTS: Maternal characteristics varied widely across neighborhood-income quintiles in both rural and urban areas. There were moderate and persistent disparities in birth outcomes across neighborhood-income quintiles in urban but not rural areas. The relative disparities in urban areas did not diminish over time for all birth outcomes and actually rose for postneonatal mortality. For example, crude RRs (95% confidence intervals) for Q5 versus Q1 in urban areas for SGA were 1.44 (1.37-1.52) in 1985-1988 and 1.41 (1.33-1.49) in 1997-2000; for postneonatal death, the corresponding results were 1.61 (1.17-2.20) and 2.20 (1.24-3.92), respectively. Most of the observed disparities could not be explained by observed maternal and pregnancy characteristics. CONCLUSION: Moderate disparities in birth outcomes by neighborhood income persist in urban areas (although not rural areas) of British Columbia, despite a universal health insurance system and generally favorable socioeconomic conditions.

Disparities in pregnancy outcomes according to marital and cohabitation status.

OBJECTIVE: To assess the risks and trends of adverse pregnancy outcomes among mothers in common-law unions versus traditional marriage relationships. METHODS: We conducted a birth cohort-based study of all 720,586 births registered in Quebec for the years 1990 to 1997. RESULTS: The proportion of births to common-law mothers more than doubled from 20% in 1990 to 44% in 1997. Preterm birth, low birth weight, small for gestational age, and neonatal and postneonatal mortality rates increased progressively from mothers legally married, to common-law unions, to lone mothers with father information, to lone mothers without father information on birth registrations. Adjusted odd ratios with 95% confidence intervals (CIs) for common-law versus legally married mothers were 1.14 (95% CI 1.11, 1.17) for preterm birth, 1.21 (95% CI 1.18, 1.25) for low birth weight, 1.18 (95% CI 1.16, 1.20) for small for gestational age, 1.07 (95% 0.97, 1.19) for neonatal death, and 1.23 (95% CI 1.04, 1.44) for postneonatal death after controlled for observed individual- and community-level characteristics. The crude and adjusted odds ratios were virtually unchanged over time. CONCLUSION: Pregnancy outcomes are worse among mothers in common-law unions versus traditional marriage relationships but better than among mothers living alone. Modest disparities in pregnancy outcomes in common-law versus traditional marriage relationships have persisted despite the striking rise in common-law unions. LEVEL OF EVIDENCE: II-2

Risks of adverse pregnancy outcomes among Inuit and North American Indian women in Quebec, 1985-97.

We used Statistics Canada's linked stillbirth, live birth and infant death files to assess the risks of adverse pregnancy outcomes among Inuit and North American Indian vs. other ethnic women in Quebec, 1985-97 (1 125 462 singleton births). Mother tongue was used to define ethnicity, with the largest French language group as the reference. Main outcome measures are adjusted odds ratios (AOR) for preterm birth, small-for-gestational-age (SGA), stillbirth, neonatal and postneonatal death controlled for maternal age, education, marital status, parity, infant sex, community size, and community-level random effects using multilevel logit models. Inuit women had higher risks of preterm birth (AOR = 1.49, 95% CI [1.25, 1.78]) and immaturity-related infant mortality (AOR = 3.03 [1.36, 6.74]), while Indian women did not. Infants of Inuit (AOR = 0.39 [0.31, 0.49]) and Indian (AOR = 0.27 [0.24, 0.31]) women had substantially lower risks of SGA. Elevated risks of stillbirth were observed among Indian women [AOR = 1.53 (1.09, 2.15)], and of postneonatal death among both Inuit (AOR = 4.45 [2.74, 7.22]) and Indian (AOR = 1.86 [1.28, 2.70]) infants. Both Inuit and Indian infants had much higher risks of sudden infant death syndrome (SIDS) and infection-related mortality. Although the absolute risks of adverse outcomes declined from 1985-87 to 1995-97, the relative disparities between aboriginal and non-aboriginal women changed little over this period. We conclude that Inuit and Indian women have different risk profiles for adverse pregnancy outcomes, and that prevention of preterm birth among Inuit women, and of SIDS and infection-related infant mortality in both aboriginal groups, are important targets for future research and intervention.