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.

Follow-up of children diagnosed with pervasive developmental disorders: stability and change during the preschool years.

Forty-one children with pervasive developmental disorders (PDDs) receiving eclectic services were assessed twice during their preschool years. Measures were compared over time for the whole group and for diagnostic subgroups: Childhood autism (CA group) and Other PDDs group. The mean intelligence quotient/developmental quotient (IQ/DQ) of the whole group was stable (P = 0.209) and scores on the Childhood Autism Rating Scale (CARS) decreased (P = 0.001). At time 2, the CA group was more impaired than the other PDDs group: autistic symptoms were more severe (P = 0.01), adaptive behavior scores were lower (P = 0.014), and a trend for lower IQ/DQs (P = 0.06). Children in this study seemed to fare better than reported in previous follow-up studies on children with autism.

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.

Recurrence of hypertensive disorder in second pregnancy.

OBJECTIVE: The purpose of this study was to investigate the recurrence of hypertensive disorders in pregnancy with regard to the type of disorder, the onset of hypertension, and the modulating effect of overweight and weight gain between pregnancies. STUDY DESIGN: Maternity records from 896 parous women with hypertensive disorders in pregnancy in the first pregnancy were reviewed to reclassify disease status and calculate odds ratios for recurrence. RESULTS: Recurrence of hypertensive disorders in pregnancy occurred in 58% to 94% of second pregnancies, depending on first pregnancy disorder. Overweight (odds ratio, 1.82) and weight gain (odds ratio, 2.20) were related to recurrence among women with gestational hypertension. Early hypertension (

Paternity change and the recurrence risk in familial hypertensive disorder in pregnancy.

OBJECTIVE: To investigate if there is an increased risk for recurrence of hypertensive disorder in pregnancy with a new partner and whether this is affected by maternal age and the interbirth interval through use of familial material. METHODS: Data on 614 multiparous women, with confirmed de novo hypertensive disorder in a first pregnancy, were used to assess the effect of paternity and interbirth interval on recurrence of hypertensive disorders. RESULTS: There were 121 women (19.7%) who had changed partner. Recurrent hypertension occurred in 318 women (64.5%) with the same partner and in 75 women (62%) with a new partner. The odds ratio (OR) for recurrence with the same partner was 1.115 (95% CI 0.739-1.680) and with a new partner 0.897 (95% CI 0.595-1.353). The mean interbirth interval was longer for women with recurrent hypertension (4.9 vs. 4.0 years, p = 0.0002). The OR for developing recurrent hypertensive disorder was 1.154 (95% CI 1.049-1.269) for every interval year with the same partner and 1.145 (95% CI 0.958-1.368) with a new partner after correction for maternal age. CONCLUSION: In women with a positive family history and previous hypertension in pregnancy, change of paternity does not influence the risk of recurrence. Increasing interbirth interval may account for a 15% recurrence risk for each year, independent of maternal age. There was no indication that a change of partner conferred any influence on the recurrence risk that is not explained with birth interval or age.