Objective: To investigate whether periconceptional maternal intake of ultra-processed foods (UPF) impairs first-trimester utero-placental vascular development, and whether macronutrients and dietary patterns substantiate the associations. Design: Prospective observational cohort. Setting: Academic hospital. Population or Sample: Ongoing pregnancies. Methods: 93 women completed a food frequency questionnaire from which we calculated percentage of energy intake from UPF, intake of energy and macronutrients and adherence to dietary patterns. We performed sequential three-dimensional power Doppler ultrasounds of the first-trimester utero-placental vasculature. VOCAL software, Virtual Reality segmentation and a skeletonization algorithm were applied to measure placental volume (PV), utero-placental vascular volume (uPVV) and generate the utero-placental vascular skeleton (uPVS). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (end-, bifurcation-, crossing- or vessel point) and used to calculate density of vascular branching. Main Outcome Measures: PV, uPVV, uPVS characteristics and density of vascular branching. Results: Fully adjusted linear mixed models showed a 10%/day higher UPF intake was associated with increased first-trimester density of vascular branching (bifurcation points: β=0.465√n, 95%CI=0.148;0.782). Higher carbohydrate intake of 10g/day was associated with increased trajectories of uPVV (β=0.017, 95%CI=0.001;0.032) and uPVS (end points (β=0.286, 95%CI=0.062;0.511), bifurcation points (β=0.004, 95%CI=0.003;0.006), vessel points (β=0.772, 95%CI=0.137;1.408). The associations were substantiated by the adherence to the “Snack” dietary pattern. Conclusions: Periconceptional maternal intake of UPF is associated with impaired first-trimester utero-placental vascular development, whereas the intake of carbohydrates and strong adherence to a ‘Snack’ dietary pattern, is positively associated with first-trimester utero-placental vascular development.

Objective To develop an evidence-based and simple screening tool to estimate calcium intake in pregnant women, suitable for use in daily clinical practice. Design Cross-sectional analysis within a cohort study Population and setting We extracted all data from the Rotterdam Periconceptional cohort (PREDICT study) conducted at the Erasmus MC, University Medical Centre in Rotterdam, the Netherlands, between November 2014 and December 2020. Methods Data was extracted from food frequency questionnaires. The estimated average requirement of 750 m/day was defined as the lower limit for an adequate calcium intake. We created a prediction model, using multivariable binary logistic regression with backward stepwise selection. We developed a simple screening tool based on the prediction model. Main outcome measures Probability of adequate calcium intake Results 694 participants are included, of which 201 (29%) had an adequate calcium intake. Total daily or weekly intakes of cheese, milk, and yogurt or curd were selected as predictors for the prediction model. The model had excellent discrimination (AUC 0.858), a good fit (Brier score 0.136, HL statistic p=0.499) and satisfactory calibration. The test accuracy measures were: sensitivity 80.9%, specificity 77.1%, PPV 89.7%, NPV 62.2%. A color coded digital screening tool was developed for use in clinical practice. Conclusions This evidence-based and simple screening tool is a reliable and efficient instrument to predict inadequate calcium intakes in pregnancy, which can easily be incorporated in daily clinical practice and existing pregnancy coaching platforms.

Objective: Congenital cardiac outflow defects (COD) are the largest group of congenital heart defects, with ventricular septal defect (VSD) as the most prevalent phenotype. Increased maternal age, excessive oxidative stress and inflammation are involved in the pathophysiology and enhance telomere length (TL) shortening. We aim to study the association between periconception maternal TL, as future predictive biomarker, and the risk of having a child with COD. Design: HAVEN-study, a multicenter case-control triad study conducted in the Netherlands. Setting and population: 306 case mothers of a child with COD and 424 control mothers of a child without a congenital malformation were selected. Methods: TL was estimated, on DNA from venous blood samples, by qPCR. Multivariable logistic regression was used to compute crude and adjusted odds ratios (OR) per standard deviation (SD) decrease between maternal T/S ratio and COD and VSD risk. Main outcome measures: The risk of COD in offspring. Results: A significant association was shown between maternal TL shortening (per standard deviation) and a 29% increased risk of VSD in offspring (OR 1.29(95% CI 1.04-1.61), P= 0,02), which remained significant after additional adjustment for maternal age (adjOR 1.25(95% CI 1.01-1.55), P= 0,04). No association between maternal TL and the risk of overall COD in offspring was observed. Conclusion: Shortening of maternal TL, due to maternal conditions including age, is associated with an approximately 1.3-fold increased risk, per SD in TL-shortening, of VSD in the offspring. These findings need further confirmation in other studies on the predictive value of maternal TL.