Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.

Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10-11) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes

INFLUENCE OF COVID-19 ON PREGNANCY, LABOR AND THE CONDITION OF NEWBORNS

It has been established that the course of pregnancy in women who have undergone COVID-19 before 12 weeks of gestation is complicated by spontaneous miscarriage, the development of fetal malformations, antenatal fetal death, and every third has a violation of the uteroplacental-fetal circulation. It was revealed that infection with COVID-19 infection in earlier stages of pregnancy leads to the development of fetal growth retardation syndrome in newborns. Since pregnancy and childbirth in our region remain high enough, we continue our research to study the impact of COVID-19 infection on pregnancy, childbirth, and the condition of newborns to develop their management tactics

Study of the Effects of the Age at Menopause and Duration of Menopause on Bone Mineral Density in Postmenopausal Women in Uzbekistan

The aim of the present study was to determine whether an association exists between the duration of menopause and the age of menopause onset, and the differences in bone mineral density (BMD) in postmenopausal women. Materials and Methods: We have reviewed medical records of 112 postmenopausal women who had not taken any anti-osteoporosis treatment and/or hormone replacement therapy at the time of BMD measurement. The mean age of the postmenopausal women was 53.5±1.1 years, and the mean menopausal period was 4.5 years. The women were evaluated according to the duration of menopause at the time of BMD measurement and age at menopause onset. BMD was measured anteroposteriorly at the L1–L4 level by the dual-energy X-ray absorptiometry method. Results: According to WHO criteria, osteoporosis and osteopenia were identified in 18(16.2%) and 44(39.2%) cases, respectively; overall, 50(44.6%) women had normal BMD.At the time of BMD measurement, osteoporosis was determined in 10.3% and 29.1% of the women with menopause duration of 0–3 years and >7 years, respectively (P=0.047). The percentages for osteopenia were similar among the three different menopause durations (36.2%, 43.3% and 41.6% for 0-3 years, 4-7 years and >7 years, respectively). No differences were determined in the prevalence of osteopenia and osteoporosis in women with menopause duration of >7 years.Thirty-three percent of women with the age of menopause onset of 52 years, respectively). The frequency of osteopenia did not differ between the groups according to the age of menopause onset. Conclusion: According to our results, osteoporosis is related to the duration of menopause at the time of BMD measurement more than to the age of menopause onset among untreated postmenopausal women

Risk Assessment and Management of Venous Thromboembolism in Women during Pregnancy and Puerperium (SAVE): An International, Cross-sectional Study

International audienceThe clinical burden of obstetric venous thromboembolism (VTE) risk is inadequately established. This study assessed the prevalence and management of VTE risk during pregnancy and postpartum outside the Western world. This international, noninterventional study enrolled adult women with objectively confirmed pregnancy attending prenatal care/obstetric centers across 18 countries in Africa, Eurasia, Middle-East, and South Asia. Evaluations included proportions of at-risk women, prophylaxis as per international guidelines, prophylaxis type, factors determining prophylaxis, and physicians' awareness about VTE risk management guidelines and its impact on treatment decision. Data were analyzed globally and regionally. Physicians ( N = 181) screened 4,978 women, and 4,010 were eligible. Of these, 51.4% were at risk (Eurasia, 90%; South Asia, 19.9%), mostly mild in intensity; >90% received prophylaxis as per the guidelines (except South Asia, 77%). Women in Eurasia and South Asia received both pharmacological and mechanical prophylaxes (>55%), while pharmacological prophylaxis (>50%) predominated in Africa and the Middle-East. Low-molecular-weight heparin was the pharmacological agent of choice. Prophylaxis decision was influenced by ethnicity, assisted reproductive techniques, caesarean section, and persistent moderate/high titer of anticardiolipin antibodies, though variable across regions. Prophylaxis decision in at-risk women was similar, irrespective of physicians' awareness of guidelines (except South Asia). A majority (>80%) of the physicians claimed to follow the guidelines. More than 50% of women during pregnancy and postpartum were at risk of VTE, and >90% received prophylaxis as per the guidelines. Physicians are generally aware of VTE risk and comply with guidelines while prescribing prophylaxis, although regional variations necessitate efforts to improve implementation of the guidelines

Variants in the fetal genome near FLT1 are associated with risk of preeclampsia

Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10(-11)) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.Peer reviewe

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Abstract Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia