Background The first 1000 days of life form a critical period for lifelong health, growth and neurodevelopment. Prenatal exposure to toxic substances, such as alcohol (PAE), can impact both short- and long-term offspring health. However, knowledge on PAE and brain development in early life is limited. Objectives This systematic review investigated associations between PAE and brain development during the first 1000 days of life. Search strategy This systematic review was registered in PROSPERO at CRD42022355144. The literature search was performed from inception until February 2024, in EMBASE, MEDLINE, Web of Science, PsycINFO, and the Cochrane Library. Selection criteria Studies investigating PAE and brain development during the first 1000 days, using ultrasound, magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI) were included. Data collection and analysis Our search initially identified 3618 articles, of which 16 were included. Collected information extracted from the articles included: study period, study population, design, methodology, exposure information, imaging type (ultrasound, MRI or DTI), brain measurements and study results. Main results The findings suggest inconsistent associations between PAE and early brain development. Ultrasound studies on PAE and brain size report no clear relations. Some postnatal MRI studies reported smaller thalami, amygdalae and hippocampi in alcohol exposed neonates. Postnatal DTI studies ( n=5) examining network integrity and connectivity reported bidirectional results in multiple brain networks. Conclusions This systematic review highlights the need for further research on first trimester brain development, timing and quantity of alcohol exposure. Longitudinal assessments and standardized procedures for neuroimaging are crucial to understand the impact of PAE on early brain 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.