Background: Neurodevelopmental disorders are increasingly believed to originate from intrauterine growth restriction (IUGR). Current reviews exploring the neurodevelopmental effects of IUGR, however, are mostly based on birthweight, an inadequate proxy.Objective: We aimed to examine the association between IUGR documented in utero, and neurodevelopmental outcomes during childhood.Search strategy: Medline, CINAHL, PsycInfo and Scopus were searched for relevant studies published after 1970.Selection criteria: The analysis included studies that identified IUGR in utero, with follow‐up assessments between 1 month and 12 years of age.Data collection and analysis: Data was extracted for cognitive, behavioural, language, motor, hearing, vision or sleep outcomes. Studies were summarised separately for children born at <35 and ≥35 weeks gestation.Main results: Of 28 876 titles identified, 38 were suitable for inclusion. IUGR children born ≥35 weeks gestation scored on average 0.5 SD lower than non‐IUGR children across all neurodevelopmental assessments. IUGR children born <35 weeks of gestation scored approximately 0.7 SD lower than non‐IUGR children across all neurodevelopmental assessments. IUGR children with evidence of fetal circulatory redistribution (preferential perfusion of the brain) had more severe neurodevelopmental impairments than those born IUGR alone.Conclusions: IUGR increases the risk of neurodevelopmental impairment during childhood differentially across domains. IUGR children born preterm or with evidence of fetal circulatory redistribution are more severely affected.Tweetable IUGR is associated with an overall risk for neurodevelopmental delay in a range of neurodevelopmental domains.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function¹. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women², selected using World Health Organization recommendations for growth standards³. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age^4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline^6–8. The atlas corresponds structurally to published magnetic resonance images⁹, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks’ gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks’ gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

The International Fetal and Newborn Growth Consortium for the 21^st Century (INTERGROWTH-21^st) Project is a population-based, longitudinal study describing early growth and development in an optimally healthy cohort of 4607 mothers and newborns. At 24 months, children are assessed for neurodevelopmental outcomes with the INTERGROWTH-21^st Neurodevelopment Package. This paper describes neurodevelopment tools for preschoolers and the systematic approach leading to the development of the Package. An advisory panel shortlisted project-specific criteria (such as multi-dimensional assessments and suitability for international populations) to be fulfilled by a neurodevelopment instrument. A literature review of well-established tools for preschoolers revealed 47 candidates, none of which fulfilled all the project's criteria. A multi-dimensional assessment was, therefore, compiled using a package-based approach by: (i) categorizing desired outcomes into domains, (ii) devising domain-specific criteria for tool selection, and (iii) selecting the most appropriate measure for each domain. The Package measures vision (Cardiff tests); cortical auditory processing (auditory evoked potentials to a novelty oddball paradigm); and cognition, language skills, behavior, motor skills and attention (the INTERGROWTH-21^st Neurodevelopment Assessment) in 35–45 minutes. Sleep-wake patterns (actigraphy) are also assessed. Tablet-based applications with integrated quality checks and automated, wireless electroencephalography make the Package easy to administer in the field by non-specialist staff. The Package is in use in Brazil, India, Italy, Kenya and the United Kingdom. The INTERGROWTH-21^st Neurodevelopment Package is a multi-dimensional instrument measuring early child development (ECD). Its developmental approach may be useful to those involved in large-scale ECD research and surveillance efforts.

Background Cross-cohort comparison is an established method for improving causal inference. This study compared 2 cohorts, 1 from a high-income country and another from a middle-income country, to (1) establish whether birth exposures may play a causal role in the development of childhood attention problems; and (2) identify whether confounding structures play a different role in parent-reported attention difficulties compared with attention deficit hyperactivity disorder (ADHD) diagnoses. Methods Birth exposures included low birth weight (LBW), small-for-gestational age (SGA), small head circumference (HC) and preterm birth (PTB)). Outcomes of interest were attention difficulties (Strengths and Difficulties Questionnaire, SDQ) and ADHD (Development and Well-Being Assessment, DAWBA). Associations between exposures and outcomes were compared between 7-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK (N=6849) and the 2004 Pelotas cohort in Brazil (N=3509). Results For attention difficulties (SDQ), the pattern of association with birth exposures was similar between cohorts: following adjustment, attention difficulties were associated with SGA (OR=1.59, 95% CI 1.20 to 2.19) and small HC (OR=1.64, 95% CI 1.11 to 2.41) in ALSPAC and SGA (OR=1.35, 95% CI 1.04 to 1.75) in Pelotas. For ADHD, however, the pattern of association following adjustment differed markedly between cohorts. In ALSPAC, ADHD was associated with LBW (OR=2.29, 95% CI 1.09 to 4.80) and PTB (OR=2.33, 95% CI 1.23 to 4.42). In the Pelotas cohort, however, ADHD was associated with SGA (OR=1.69, 95% CI 1.02 to 2.82). Conclusions The findings suggest that fetal growth impairment may play a causal role in the development of attention difficulties in childhood, as similar associations were identified across both cohorts. Confounding structures, however, appear to play a greater role in determining whether a child meets the full diagnostic criteria for ADHD.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections)¹ and preventive interventions (for example, multiple-micronutrient supplementation)² that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood³. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide⁴, we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks’ gestation, against international standards^5,6, and growth and neurodevelopment up to 2 years of age^7,8. We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20–25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20–25 weeks’ gestation.