Qiu C, Gelaye B, Denis M, Tadesse MG, Fernandez MAL, Enquobahrie DA, Ananth CV, Sanchez SE, Williams MA.
Circadian clock-related genetic risk scores and risk of placental abruption [Internet]. Placenta 2015;:-.
Publisher's VersionAbstractAbstractIntroduction The circadian clock plays an important role in several aspects of female reproductive biology. Evidence linking circadian clock-related genes to pregnancy outcomes has been inconsistent. We sought to examine whether variations in single nucleotide polymorphisms (SNPs) of circadian clock genes are associated with \PA\ risk. Methods Maternal blood samples were collected from 470 \PA\ case and 473 controls. Genotyping was performed using the Illumina Cardio-MetaboChip platform. We examined 119 \SNPs\ in 13 candidate genes known to control circadian rhythms (e.g., CRY2, ARNTL, and RORA). Univariate and penalized logistic regression models were fit to estimate odds ratios (ORs); and the combined effect of multiple \SNPs\ on \PA\ risk was estimated using a weighted genetic risk score (wGRS). Results A common \SNP\ in the \RORA\ gene (rs2899663) was associated with a 21% reduced odds of \PA\ (P < 0.05). The odds of \PA\ increased with increasing wGRS (Ptrend < 0.001). The corresponding \ORs\ were 1.00, 1.83, 2.81 and 5.13 across wGRS quartiles. Participants in the highest wGRS quartile had a 5.13-fold (95% confidence interval: 3.21–8.21) higher odds of \PA\ compared to those in the lowest quartile. Although the test for interaction was not significant, the odds of \PA\ was substantially elevated for preeclamptics with the highest wGRS quartile (OR = 14.44, 95%CI: 6.62–31.53) compared to normotensive women in the lowest wGRS quartile. Discussion Genetic variants in circadian rhythm genes may be associated with \PA\ risk. Larger studies are needed to corroborate these findings and to further elucidate the pathogenesis of this important obstetrical complication.
Rice JR, Larrabure-Torrealva GT, Fernandez MAL, Grande M, Motta V, Barrios YV, Sanchez S, Gelaye B, Williams MA.
High risk for obstructive sleep apnea and other sleep disorders among overweight and obese pregnant women. BMC pregnancy and childbirth 2015;15
AbstractObstructive sleep apnea (OSA), a common and serious disorder in which breathing repeatedly stops during sleep, is associated with excess weight and obesity. Little is known about the co-occurrence of OSA among pregnant women from low and middle-income countries.
Ananth CV, Keyes KM, Hamilton A, Gissler M, Wu C, Liu S, Luque-Fernandez MA, Skjærven R, Williams MA, Tikkanen M, Cnattingius S.
An international contrast of rates of placental abruption: an age-period-cohort analysis. PLoS One 2015;10(5):e0125246.
AbstractBACKGROUND: Although rare, placental abruption is implicated in disproportionately high rates of perinatal morbidity and mortality. Understanding geographic and temporal variations may provide insights into possible amenable factors of abruption. We examined abruption frequencies by maternal age, delivery year, and maternal birth cohorts over three decades across seven countries.
METHODS: Women that delivered in the US (n = 863,879; 1979-10), Canada (4 provinces, n = 5,407,463; 1982-11), Sweden (n = 3,266,742; 1978-10), Denmark (n = 1,773,895; 1978-08), Norway (n = 1,780,271, 1978-09), Finland (n = 1,411,867; 1987-10), and Spain (n = 6,151,508; 1999-12) were analyzed. Abruption diagnosis was based on ICD coding. Rates were modeled using Poisson regression within the framework of an age-period-cohort analysis, and multi-level models to examine the contribution of smoking in four countries.
RESULTS: Abruption rates varied across the seven countries (3-10 per 1000), Maternal age showed a consistent J-shaped pattern with increased rates at the extremes of the age distribution. In comparison to births in 2000, births after 2000 in European countries had lower abruption rates; in the US there was an increase in rate up to 2000 and a plateau thereafter. No birth cohort effects were evident. Changes in smoking prevalence partially explained the period effect in the US (P = 0.01) and Sweden (P<0.01).
CONCLUSIONS: There is a strong maternal age effect on abruption. While the abruption rate has plateaued since 2000 in the US, all other countries show declining rates. These findings suggest considerable variation in abruption frequencies across countries; differences in the distribution of risk factors, especially smoking, may help guide policy to reduce abruption rates.
Gelaye B, Larrabure-Torrealva GT, Qiu C, Luque-Fernandez MA, Peterlin LB, Sanchez SE, Williams MA.
Fasting Lipid and Lipoproteins Concentrations in Pregnant Women With a History of Migraine [Internet]. Headache: The Journal of Head and Face Pain 2015;:n/a–n/a.
Publisher's VersionAbstractBackground Migraine is associated with a number of cardiometabolic risk factors including abnormalities in lipid metabolism. However, little is known about these associations among pregnant migraineurs. We conducted the present study to evaluate the extent to which altered lipid profiles are associated with history of migraine among pregnant women. Methods A cohort of 1062 Peruvian women were interviewed at 24-28 weeks of gestation. Migraine status was classified based on the International Classification of Headache Disorders-II diagnostic criteria. Serum lipid concentrations were measured enzymatically using standardized assays. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) as measures of associations of migraine status with varying concentrations of lipids and lipoproteins during pregnancy. Results Approximately 18.5% of the study participants were identified as migraineurs (196 of 1062). Maternal serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol : HDL ratio were all statistically significantly elevated among pregnant migraineurs compared with pregnant non-migraineurs. In multivariate adjusted models, pregnant women with migraine had higher odds of elevated total cholesterol, LDL, and total cholesterol : HDL ratio as compared with pregnant women without migraine. For instance, the AOR and 95% CI for successive quartiles of the total cholesterol associated with history of migraine were Q2 (219-247 mg/dL): 1.05 (0.64-1.70), Q3 (248-281 mg/dL): 1.16 (0.72-1.86), and Q4 (≥282 mg/dL): 1.87 (1.20-2.91) with the lowest quartile (<219 mg/dL) as the referent group (P value for trend = .003). Obese women with elevated total cholesterol (≥282 mg/dL) were more likely to be migraineurs (OR = 3.71; 95% CI 1.58-8.71) as compared with non-obese women with lower total cholesterol (<219 mg/dL). Similar elevated odds of migraine were observed for obese women with elevated LDL cholesterol, elevated triglycerides and high total cholesterol : HDL ratio. Conclusion Pregnant migraineurs had elevated odds of dyslipidemia, particularly hypercholesterolemia, elevated LDL, and total cholesterol : HDL ratio as compared with pregnant non-migraineurs. The observed associations were more pronounced among obese migraineurs. Our findings add to the accumulating evidence of adverse cardiometabolic risk profiles among migraineurs and extend these associations to pregnant women.
Luque-Fernandez MA, Ananth CV, Jaddoe VWV, Gaillard R, Albert PS, Schomaker M, McElduff P, Enquobahrie DA, Gelaye B, Williams MA.
Is the fetoplacental ratio a differential marker of fetal growth restriction in small for gestational age infants?. Eur J Epidemiol 2015;
AbstractHigher placental weight relative to birthweight has been described as an adaptive mechanism to fetal hypoxia in small for gestational age (SGA) infants. However, placental weight alone may not be a good marker reflecting intrauterine growth restriction. We hypothesized that fetoplacental ratio (FPR)-the ratio between birthweight and placental weight-may serve as a good marker of SGA after adjustment for surrogates of fetal hypoxemia (maternal iron deficiency anemia, smoking and choriodecidual necrosis). We conducted a within-sibling analysis using data from the US National Collaborative Perinatal Project (1959-1966) of 1,803 women who delivered their first two (or more) consecutive infants at term (n = 3,494). We used variance-component fixed-effect linear regression models to explore the effect of observed time-varying factors on placental weight and conditional logistic regression to estimate the effects of the tertiles of FPRs (1st small, 2nd normal and 3rd large) on the odds of SGA infants. We found placental weights to be 15 g [95 % confidence interval (CI) 8, 23] higher and -7 g (95 % CI -13, -2) lower among women that had anemia and choriodecidual necrosis, respectively. After multivariable adjustment, newborns with a small FPR (1st-tertile ≤7) had twofold higher odds of being SGA (OR 2.0, 95 % CI 1.2, 3.5) than their siblings with a large FPR (3nd-tertile ≥9). A small FPR was associated with higher odds of SGA, suggesting that small FPR may serve as an indicator suggestive of adverse intrauterine environment. This observation may help to distinguish pathological from constitutional SGA.