Background: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placentamediated complications could exist. Objective: To determine the association of fetal sex with multiple maternal pregnancy complications. Search strategy: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies. Selection criteria: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies. Data collection and analyses: Data were extracted by 2 independent reviewers using a predesigned data collection form. Main results: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition. Conclusion: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus. Funding: None.

BackgroundThe objective of this study was to assess whether sex-specific differences in fetal and infant growth exist.MethodsThis study was embedded in the Generation R Study, a population-based prospective birth cohort. In total, 8556 live singleton births were included. Fetal growth was assessed by ultrasound. During the first trimester, crown-rump-length (CRL) was measured. In the second and third trimester of pregnancy head circumference (HC), abdominal circumference (AC) and femur length (FL) were assessed. Information on infant growth during the first 2 years of life was obtained from Community Health Centers and included HC, body weight and length.ResultsIn the first trimester, male CRL was larger than female CRL (0.12 SD [95% CI 0.03,0.22]). From the second trimester onwards, HC and AC were larger in males than in females (0.30 SD [95% CI 0.26,0.34] and 0.09 SD [95% CI 0.05,0.014], respectively). However, FL in males was smaller compared to female fetuses (0.21 SD [95% CI 0.17,0.26]). Repeated measurement analyses showed a different prenatal as well as postnatal HC growth pattern between males and females. A different pattern in body weight was observed with a higher body weight in males until the age of 12 months where after females have a higher body weight.ConclusionsSex affects both fetal as well as infant growth. Besides body size, also body proportions differ between males and females with different growth patterns. This sexual dimorphism might arise from differences in fetal programming with sex specific health differences as a consequence in later life.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0119-1) contains supplementary material, which is available to authorized users.

Objective To investigate fetal sex dependency of maternal vascular adaptation to pregnancy as assessed by uteroplacental vascular resistance and maternal blood pressure.Design Prospective population-based cohort study.Setting Rotterdam, the Netherlands.Population In total, 8224 liveborn singleton pregnancies were included.Methods Maternal vascular adaptation was assessed in all trimesters of pregnancy. Pregnancies were stratified into being either complicated by the placental syndrome (i.e. pre-eclampsia, fetal growth restriction or preterm birth, n = 1229) or uncomplicated (n = 6995).Main outcome measures First trimester: blood pressures. Second trimester: blood pressures, pulsatility index of the uterine artery (PI-UtA). Third trimester: blood pressures, PI-UtA, presence of notching in the uterine artery.Results In women carrying a male fetus PI-UtA was higher than in women with a female fetus in the total group (second trimester P < 0.001, third trimester P = 0.005). Effect estimates differed between women with or without the placental syndrome. In the total group, women with a male fetus more often showed notching in the Doppler resistance pattern (odds ratio 1.42, 95% confidence interval 1.17-1.72). Different blood pressure patterns were observed between pregnant women with a male fetus and pregnant women with a female fetus and between complicated pregnancies and uncomplicated pregnancies.Conclusion Fetal sex is significantly associated with maternal vascular adaptation to pregnancy with differential effects in uncomplicated pregnancies and in pregnancies complicated by the placental syndrome.Keywords Blood pressure, fetal growth restriction, fetal sex, preeclampsia, pulsatility index, spontaneous preterm birth, notching. Please cite this paper as: Broere-Brown ZA, Schalekamp-Timmermans S, Hofman A, Jaddoe VWV, Steegers EAP. Fetal sex dependency of maternal vascular adaptation to pregnancy: a prospective population-based cohort study.

Background: Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of mid-pregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in mid-pregnancy identify not only a subset of women at risk for pregnancy complications, but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome. Methods:In a population-based prospective cohort study of 5529 women, we computed gestational-age-adjusted multiple of the medians of early pregnancy and mid-pregnancy PlGF concentrations. Information on pregnancy complications (pre-eclampsia, small for gestational age and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy we measured maternal systolic and diastolic blood pressure (SBP and DBP), cardiac structure (aortic root diameter [AOD], left atrial diameter [LAD], left ventricular mass [LV mass] and fractional

Background Small for gestational age (SGA) is frequently used to define fetal growth restriction (FGR). However, FGR describes a slowdown in fetal growth and is not synonymous with SGA, which may introduce misclassification. We investigated the effect of both on delivery and childhood outcomes. Methods From a prospective population-based cohort study we included 7959 live singleton births with data available on second trimester estimated fetal weight (EFW) and birth weight. We used a decrease in growth of > 40 percentiles between second trimester EFW and birthweight to define a deceleration in growth. SGA was defined as birthweight