BACKGROUND:Exposure to heat and cold are associated with adverse birth outcomes, but whether ambient temperature affects embryonic and early fetal development remains unclear. We aimed to examine the association between ambient temperature exposure during early pregnancy and crown-rump length (CRL). METHODS:Data from the Generation R Next Study (2017-2021) were analysed, with findings replicated in the Generation R Study (2002-2006), both population-based cohorts based in Rotterdam, The Netherlands. Weekly mean temperatures were modeled from the last menstrual period onward at a spatial resolution of 100 × 100 m by using the UrbClim™ model. The CRL was measured via 2D ultrasound at approximately 8, 10, and 12 weeks' gestation in pregnancies with regular menstrual cycles. Distributed lag nonlinear models were applied. RESULTS:In Generation R Next (N = 1378; mean maternal age 31.9 years), higher temperatures during the first 9 weeks were associated with a smaller CRL at 12 weeks {e.g. -7.2 mm [95% confidence interval (CI) -12.0, -2.3] at 19.2 vs 9.0°C during weeks 1-6}. Colder exposures during the first 11 weeks were also associated with a smaller CRL [-7.6 mm (95% CI -11.9, -3.3) at 3.6 vs 9.0°C during weeks 1-11]. No associations were observed for CRL at 8 or 10 weeks. Similar associations with cold, but not heat, were observed in the replication cohort (N = 1520). CONCLUSION:Moderate cold and heat exposure during early pregnancy may affect fetal development as early as the first trimester. These findings indicate that early gestational development may be sensitive to ambient temperature and, as environmental conditions shift, may have potential clinical implications for birth outcomes and long-term health.

As efforts to support pregnancy planning and improve preconception health are increasing at scale, appropriate systems to monitor progress are required. Despite developments in a few countries, no surveillance systems currently in operation are using a comprehensive set of indicators for monitoring preconception health. This Review describes relevant indicators, reflecting both system-level and individual-level factors, that can be drawn from routine data sources to form the basis for developing new surveillance systems. We present a new framework for national and international surveillance that incorporates, for the first time, community perspectives on the factors that matter most before pregnancy and parenthood. Finally, we describe an international collaboration working towards a core set of indicators that can be compared across low-income, middle-income, and high-income countries, and discuss future directions to enhance and expand international monitoring of pregnancy planning and preconception health.

A wide spectrum of predictors of childhood overweight and obesity has been identified over past decades, yet a quantitative overview of multidisciplinary predictors is missing, and the relative importance and their collective contribution to childhood obesity remains unclear. We synthesized evidence from 93 published studies from the Generation R Study, a population-based prospective cohort from early-pregnancy onwards in the Netherlands, to provide a quantitative overview of 210 predictors across preconception and childhood associated with body mass index (BMI) in mid-childhood and selected 59 candidate predictors. Then, we further identified 32 key predictors for either zBMI or weight status using model search algorithms and built prediction models with data from the same cohort. Associations of note were identified among predictors in preconception and prenatal parental health, early-life weight, and child behavior domains. An interquartile range increase in parental prepregnancy BMI (maternal β = 0.17, 95% CI: 0.14, 0.20; paternal β = 0.17, 95% CI: 0.14, 0.21), early-life weight (e.g., zBMI at age 2y β = 0.28, 95% CI: 0.23, 0.33), and food responsiveness (β = 0.25, 95% CI: 0.21, 0.28) were positively associated with mid-childhood BMI, and satiety responsiveness was negatively associated (β = -0.18, 95% CI: -0.21, -0.15). Together, identified key predictors accounted for 49.2% of the variance of BMI and 33.7% of the variance of the odds of overweight and obesity at the age of 10 years. Multimodal interventions targeting parental BMI before pregnancy, early adiposity rebound, and management of appetite in early childhood may be most effective in maintaining a healthy weight during childhood.

Study question: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? Summary answer: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. What is known already: First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. Study design, size, duration: This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. Participants/materials, setting, methods: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). Main results and the role of chance: Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints beta = 0.017, 95% CI [0.009; 0.025], bifurcation points beta = 0.012, 95% CI [0.006; 0.018], crossing points beta = 0.017, 95% CI [0.008; 0.025], vessel points beta = 0.01, 95% CI [0.002; 0.008], and total vascular length beta = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values <= 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV beta = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV beta = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV beta = -20. 727, 95% CI [-32.771; -8.683], bifurcation points: uPVV beta -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV beta = -48.604 95% CI [-74.246; -22.961])), all P-values < 0.05. After stratification, the associations were observed in natural conceptions specifically. Limitation, reasons for caution: Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. Wider implications of the findings: Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. Study funding/competing interest(s): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest.

Abstract Background In Europe, women are more likely to be unemployed compared to men. Also, they more often hold part-time employment. After pregnancy and childbirth, women often reduce their working hours further or even exit the workforce altogether. This not only impacts their individual career, financial stability, and economic independence, but also their own health and well-being and that of their offspring. Objectives We aim to study the patterns of women’s work resumption in the first year after childbirth, and if sick leave during pregnancy and birth outcomes small for gestational age (SGA) and preterm birth play a role in this. Data from Statistics Netherlands and the Dutch Perinatal Registry from 114,722 Dutch pregnant women in paid employment (2016) were used for the analyses. Next to descriptive analyses, multivariate regression was used to assess which factors contribute to economic independence one year after childbirth. Results After pregnancy, over 50% of women reduced their working hours, and 12% became unemployed. The largest reduction was found in the group working fulltime (from 31 to 11%), in contrast, the group working 20-25 hours per week increased from 19 to 28% one year after childbirth. Among the women with sick leave during pregnancy (11%), the decrease in working hours was more pronounced and almost 40% of them became unemployed. The percentage of women being economically independent changed from 88% at the onset of pregnancy to 78% one year after childbirth. Next to employment factors (working hours and contract type), migration background and lower education were associated with lower odds of economic independence. Moreover, sick leave during pregnancy and having a SGA baby also reduced the odds of economic independence. Conclusions After pregnancy, women tend to work less than before, or even exit the workforce, with considerable impact on their economic independence. This is even more pronounced in the group with sick leave during pregnancy. Key messages • Despite paid maternity leave, pregnancy and childbirth negatively impact work force participation in women. • The need for sick leave during pregnancy is predictive of reduced work resumption and economic independence one year after pregnancy.

Creation of objective tools may improve the predictive ability of prenatal ultrasound to predict postnatal renal function.

To investigate associations between prenatal alcohol exposure (PAE) and longitudinal fetal cerebellar and corpus callosum growth, focusing on timing and amount of PAE. In addition, associations between PAE and cognitive development of one-year-old infants were investigated. A prospective cohort study was conducted in a predefined community, in South Africa. Our study, including 1,698 pregnant women, is a sub-study of this cohort. Three-dimensional fetal brain ultrasounds were performed during three antenatal visits, to measure the transcerebellar diameter (TCD), cerebellar volume (CV) and corpus callosum length (CCL). PAE was assessed both as an accumulative parameter, and separately per trimester, using the validated timeline follow back method. Linear mixed models, adjusted for confounders, were applied with both repeated assessments of PAE and fetal brain growth outcomes. This enabled us to calculate TCD, CV and CCL differences between alcohol exposed fetuses and controls. In addition, cognitive development in infants was measured using the Mullen Scales of Early Learning. Measurements and data analyses are still ongoing, preliminary analyses were performed on a subset. Second trimester PAE was associated with a smaller cerebellar volume, when compared to controls. PAE was associated with a smaller TCD, only when exposed to heavy drinking (> 50 drinks in pregnancy). PAE-infants scored lower on language and motor skills, compared to controls. We found no association between PAE and corpus callosum length. Preliminary results indicate that second trimester PAE is associated with fetal cerebellar growth. The CV might be a more sensitive marker in detecting PAE effects, since the TCD was only associated when exposed to heavy drinking. Our results suggest that potential consequences of PAE on brain growth may already be detectable before birth. In addition, lower cognitive development scores during infancy may indicate that these effects remain present during the first year of life.

Many congenital anomalies can already be detected during the first trimester of pregnancy using ultrasound techniques with concomitant implications for diagnostics, counselling and follow-up for future parents (e.g. early reassurance). Three-dimensional ultrasound and Virtual Reality (VR) as innovative technology provide improved visualisation and possible improved detection of congenital anomalies. Performing a multicentre randomised clinical trial (RCT), we aimed to compare health-related quality of life (HRQoL) and healthcare costs in pregnant women who, in addition to the standard regimen, underwent an additional 3D VR first trimester anomaly scan (FTAS). Women with a high risk for congenital anomalies were included. Participants were randomly assigned to the control arm (second trimester anomaly scan (STAS) or the intervention arm (STAS + additional 3D VR FTAS). The HRQoL was assessed at 4 different moments during pregnancy, using validated questionnaires on anxiety, depression and health status. Only direct healthcare costs were assessed. 1,683 participants were randomised and 1,647 were eligible for analysis. Regarding HRQoL, there was a significantly lower state anxiety in the intervention group (βSTAI = -0.358, 95% CI -0.692; -0.024, p = 0.035). There was a trend towards lower depression and anxiety scores (βHADS-depression=-0.273, 95% CI -0.600;0.055, p = 0.103; βHADS-anxiety=-0.045, 95% CI -0.094;0.004, p = 0.072). The healthcare costs showed no significant difference (control vs. intervention: €7916 vs. €7938, p = 0.941). Compared to care as usual, an additional 3D VR FTAS significantly lowers anxiety scores and does not increase the total healthcare costs. These results favour implementation of 3D VR FTAS in a high-risk population.

Background Living in socially disadvantaged circumstances has a widespread impact on one’s physical and mental health. That is why individuals living in this situation are often considered vulnerable. When pregnant, not only the woman’s health is affected, but also that of her (unborn) child. It is well accepted that vulnerable populations experience worse (perinatal) health, however, little is known about the lived adversities and health of these vulnerable individuals. Objectives With this article, insights into this group of highly vulnerable pregnant women are provided by describing the adversities these women face and their experienced well-being. Methods Highly vulnerable women were recruited when referred to tailored social care during pregnancy. Being highly vulnerable was defined as facing at least three different adversities divided over two or more life-domains. The heat map method was used to assess the interplay between adversities from the different life domains. Demographics and results from the baseline questionnaires on self-sufficiency and perceived health and well-being were presented. Results Nine hundred nineteen pregnant women were referred to social care (2016–2020). Overall, women had a median of six adversities, distributed over four life-domains. The heat map revealed a large variety in lived adversities, which originated from two parental clusters, one dominated by financial adversities and the other by a the combination of a broad range of adversities. The perceived health was moderate, and 25–34% experienced moderate to severe levels of depression, anxiety or stress. This did not differ between the two parental clusters. Conclusions This study shows that highly vulnerable pregnant women deal with multiple adversities affecting not only their social and economic position but also their health and well-being.

Methods: We evaluated the three different trajectories against a referent, defined as no abrupt change in growth trajectory and EFW or AC between the 25th and 75th centile at the final scan.The three trajectories were categorised as Group 1: SGA fetus (EFW or AC persistently < 10th centile) with appropriate forward growth trajectory; Group 2: Decreased growth trajectory with decline in EFW or AC ≥50 centiles and EFW or AC ≥10th centile at the last scan; and Group 3: Decreased growth trajectory with decline in EFW or AC ≥50 centiles, and EFW or AC < 10th centile at the last scan.Trajectories were estimated on two scans or more performed past 18 weeks and over a minimum of 4 weeks.Study outcomes were stillbirth, perinatal mortality (stillbirth or neonatal death), birth of an SGA infant and severe neonatal morbidity.Associations were analysed using logistic regression. Results:The study comprised 5319 singleton infants birthed between 32 and 42 gestational weeks.Compared with the referent, the odds of perinatal mortality were significantly increased in Group 2 (aOR 4.00, 95% CI 1.36-11.22)and Group 3 (aOR 7.71, 95% CI 2.39-24.91)).The odds of stillbirth were only increased in Group 3 (aOR 5.69, 95% 1.55-20.93).In contrast, the odds of perinatal mortality were not significantly increased for infants in Group 1.The odds of an SGA infant at birth were increased in all three groups but highest in Group 1 (aOR 111.86,) and Group 3 (aOR 40.63, 95% CI 29.01-56.92),with 1 in 2 having a birthweight < 3rd centile.The odds of severe neonatal morbidity were only increased in Groups 1 and 3. Conclusions: Assessment of fetal growth trajectory in the last half of pregnancy can identify infants at increased odds of SGA at birth, severe neonatal morbidity, and perinatal mortality.

The prediction model provides useful information for counselling twin pregnancies regarding their risk for GDM that is above the general twin population.