Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. Although studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in PE remains controversial. LMWH may convey beneficial effects in PE independent of their anticoagulant activity, possibly by inhibiting inflammation. Here, we evaluated whether LMWH inhibit placental thromboinflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle–induced and platelet-dependent PE-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation, and improves trophoblast proliferation in vivo and in vitro. Moreover, LMWH inhibits platelet-independent trophoblast NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. Mechanistically, LMWH activates via heparin-binding epidermal growth factor (HBEGF) signaling the PI3-kinase-AKT pathway in trophoblasts, thus preventing inflammasome activation. In human PE placental explants, inflammasome activation and PI3-kinase-AKT signaling events were reduced with LMWH treatment compared with those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates PE-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in PE and identify a signaling mechanism through which LMWH ameliorates PE, thus providing a rationale for the use of LMWH in PE.
Background: Pregnancy and the first year after giving birth are marked by physiological and psychological changes. While it is well known that energy requirements change during this time, the question of how a woman’s diet actually changes from pregnancy until 1 year postpartum has been left virtually unexplored. The present study employs a longitudinal design to investigate these changes. Methods: Data were collected within the framework of the LIFE Child study (Leipzig, Germany). The diet composition and culture of eating of 110 women were assessed at 3 time points: in the 24th week of pregnancy, 3 months after giving birth (breastfeeding period), and 12 months after giving birth (after weaning). We assessed differences in nutritional health (Nutritional Health Score, NHS) and the consumption of different food items at each of these time points. We also investigated associations between nutritional health and age, socio-economic status (SES), BMI before pregnancy, and previous births at all three time points. Results: The analyses revealed high correlations in the NHS values between the three time points (rhot0/t1 = .55, rhot0/t2 = .60). On average, nutritional health was lower in the breastfeeding period than during pregnancy. In more detail, women reported less healthy levels of treats and white bread consumption and a higher frequency of snacking in the breastfeeding period than during pregnancy. In contrast, overall nutritional health did not differ significantly between pregnancy and the time after weaning. Increased age was associated with a healthier diet during pregnancy, and a high SES was associated with healthier diet after weaning. Furthermore, the increase in nutritional health from the breastfeeding period to the time after weaning was significantly stronger in women with a higher BMI. We observed no significant associations between dietary nutritional health and previous births. Conclusions: The present findings suggest that higher energy requirements in the breastfeeding period are met by consuming high-calorie and unhealthy food products rather than healthy and nutrient-rich food. Young mothers should be supported in taking care of their own nutritional health during the challenging time of breastfeeding and caring for a newborn child.
Background: While a regular menstrual cycle is an indicator of good health, menstrual dysfunction (MD) and wrong beliefs regarding hormonal contraceptives (HC) are quite common among elite female athletes and threaten their health. This study aimed to (1) identify the prevalence of current and lifetime MD in various sports disciplines, (2) investigate variables that are associated with the prevalence of MD, (3) study the current practice of HC use among elite German female athletes. Methods: 584 German elite female athletes (mean 20.7 ± 4.9 years) from 64 different sports completed an online questionnaire to assess gynecological health characteristics, history of MD, and the use of HC. Results: Sixty-nine percent of athletes not using HC reported a regular menstrual cycle, while oligomenorrhea was currently reported in 13%, secondary amenorrhea in 8%, primary amenorrhea in 2% and polymenorrhea in 8%. The current prevalence of primary amenorrhea differed between sports disciplines (p = 0.002), while oligomenorrhea (p = 0.828) and secondary amenorrhea (p = 0.848) did not. The lifetime prevalence of primary amenorrhea (10%) and oligomenorrhea (74%) differed significantly between sports disciplines (p < 0.001 and p = 0.001), while secondary amenorrhea (40%) did not (p = 0.298). The current and lifetime prevalence of primary amenorrhea was higher in aesthetic sports disciplines, while the lifetime prevalence of oligomenorrhea was higher in endurance disciplines. Factors associated with lower prevalences of MD were menstrual cycle tracking (p < 0.001), higher gynecological age (p < 0.001), regular gynecological health screenings (p = 0.008), and a diagnosed eating disorder (p = 0.037). Twenty-nine percent of these elite athletes used HC, of whom 15% claimed to use HC as a treatment for MD. Conclusion: Elite female athletes from a variety of sports disciplines, not just from endurance and aesthetic sports, are at high risk of developing MD. Given the high percentage of athletes using HC to treat MD, educating athletes, coaches, others from the support team and parents about the risk and prevention of MD and the effects of HC in the context of elite sports may improve gynecological health among elite athletes.