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Problem: A handful of studies report sexual dimorphism in the maternal angiogenic profile possibly influencing placental development and preeclampsia risk. This secondary analysis explored associations between fetal sex and soluble fms-like tyrosine kinase-1 (sFLT) and endoglin (9-35 weeks gestation) using data from a nested case-control study within the Danish National Birth Cohort., Method of Study: A total of 448 preeclamptic women and 328 normotensive women had data on sFLT and endoglin. Preeclampsia was defined by blood pressure ≥140/90 mm Hg and proteinuria (≥0.3g or 300 mg/24 h.). Generalized linear models adjusting for gestational age of blood draw, body mass index, maternal age, and smoking determined associations between fetal sex and log-transformed biomarkers., Results: Male fetal sex is associated with 11% lower sFLT levels (β = -0.11, P = 0.03) in preeclamptic women. There were no differences observed in normotensive women. We found no statistically significant differences in endoglin by fetal sex among groups., Conclusion: Our results are similar with other studies suggesting that women with female fetuses have increased sFLT levels. However, significant difference was only among women with preeclampsia. This study was exploratory and longitudinal investigations across pregnancy are required to understand the relationship between fetal sex and systemic maternal angiogenic biomarkers., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Leptin, an adipocyte-derived hormone, plays an important role in reproduction and angiogenesis. Studies examining leptin in preeclampsia are inconsistent, possibly because of small sample sizes and variability in sampling and outcome. We conducted a nested case-control study to examine associations between serum leptin (measured: 9-26 weeks gestation) and preeclampsia among 430 primiparous preeclamptic women and 316 primiparous normotensive controls from the Danish National Birth Cohort. Median (interquartile range) leptin concentrations were calculated. Associations between leptin and preeclampsia (blood pressure ≥140/90 mm Hg), term preeclampsia (preeclampsia and delivery ≥37 weeks gestation), or preterm preeclampsia (preeclampsia and delivery <37 weeks gestation) were examined using generalized linear models adjusting for body mass index, gestational age at blood draw, maternal age, smoking, and socio-occupational status. As leptin is increased in obese women and the risk of preeclampsia increases with body mass index, we used the Sobel test to examine whether leptin is a mediator of this relationship. After adjustments, leptin concentrations were significantly higher in women with preeclampsia (30.5 [24.6]; P=0.0117) and term preeclampsia (30.4 [24.9]; P=0.0228) compared with controls (20.9 [28.3]). There was no significant difference between preterm preeclampsia (30.6 [23.4]; P=0.2210) and controls. Leptin is a possible mediator of the association between body mass index and preeclampsia (P=0.0276). Leptin concentrations are higher in women with preeclampsia compared with normotensive controls and may mediate some of the relationship between body mass index and preeclampsia., (© 2014 American Heart Association, Inc.)

Background: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive., Methods: We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided., Results: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91)., Conclusions: Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.

Objective: Eclampsia has been found to be a strong risk factor for epilepsy in the offspring, but it is unclear whether the risk also applies to the preceding condition, preeclampsia., Methods: We conducted a population-based cohort study of 1537860 singletons born in Denmark (1978-2004). Information on preeclampsia (mild, severe, and unspecified), eclampsia, and epilepsy was obtained from the Danish National Hospital Register. Information on gestational age, birth weight, and Apgar score was obtained from the Danish Medical Birth Registry. We used Cox proportional hazard models to estimate the incidence rate ratio of epilepsy for children who were exposed to preeclampsia or eclampsia in prenatal life., Results: We identified 45288 (2.9%) children who were exposed to preeclampsia (34823 to mild, 7043 to severe, and 3422 to unspecified preeclampsia) and 654 (0.04%) to eclampsia during their prenatal life. We identified 20260 people who received a diagnosis of epilepsy during up to 27 years of follow-up in the entire cohort. Prenatal exposure to preeclampsia was associated with an increased risk for epilepsy among children with a gestational age at birth of at least 37 weeks. For mild preeclampsia, the incidence rate ratios were 1.16 among children born at term and 1.68 for children born postterm; for severe preeclampsia, the incidence rate ratios were 1.41 among children born at term and 2.57 among children born postterm. No associations between preeclampsia and epilepsy were found among children who were born preterm. Eclampsia was associated with epilepsy with an incidence rate ratio of 1.29 for children born at term and 5.03 for children born postterm., Conclusions: Prenatal exposure to both preeclampsia and eclampsia was associated with an increased risk of epilepsy in children born after 37 weeks of gestation.