Iron supplementation is commonly recommended for the prevention and treatment of maternal iron deficiency (ID) or iron deficiency anemia (IDA). However, the impacts of prophylactic of therapeutic prenatal iron supplementation on child neurodevelopment in upper middle-income (UMI) and high-income countries (HICs), where broad nutritional deficiencies are less common, are unclear. To investigate this, we conducted a systematic review, searching four databases (Medline, CINAHL, EMBASE, Cochrane Library) through 1 May 2023. Randomized controlled trials (RCTs) assessing oral or intravenous iron supplementation in pregnant women reporting on child neurodevelopment (primary outcome: age-standardized cognitive scores) were eligible. We included three RCTs (five publications) from two HICs (Spain and Australia) (N = 935 children; N = 1397 mothers). Due to clinical heterogeneity of the RCTs, meta-analyses were not appropriate; findings were narratively synthesized. In non-anemic pregnant women, prenatal iron for prevention of IDA resulted in little to no difference in cognition at 40 days post-partum (1 RCT, 503 infants; very low certainty evidence). Similarly, the effect on the intelligence quotient at four years was very uncertain (2 RCTs, 509 children, very low certainty evidence). No RCTs for treatment of ID assessed offspring cognition. The effects on secondary outcomes related to language and motor development, or other measures of cognitive function, were unclear, except for one prevention-focused RCT (302 children), which reported possible harm for children\'s behavioral and emotional functioning at four years. There is no evidence from UMI countries and insufficient evidence from HICs to support or refute benefits or harms of prophylactic or therapeutic prenatal iron supplementation on child neurodevelopment.

OBJECTIVE: Many copy number variants (CNVs) are reported to cause a variety of neurodevelopmental disabilities including intellectual disability, developmental delay, autism and other phenotypes with incomplete penetrance, so not all individuals with a pathogenic CNV are affected. Penetrance estimates vary between studies. A systematic review was conducted to clarify CNV penetrance for 83 recurrent CNVs.
METHODS: A systematic review using PRISMA guidelines (PROSPERO #CRD42021253955) was conducted to identify penetrance estimates for CNVs associated with neurodevelopment. Pooled analysis was performed using forest plots. The Ottawa Risk of Bias Assessment facilitated evaluation.
RESULTS: Fifteen studies were reviewed in detail with nine affected cohorts pooled and compared against the gnomAD v4.0 CNV control cohort of 269,885 individuals. Several CNVs previously associated with non-statistically significant penetrance estimates now exhibit statistically significant differences, contributing to emerging evidence for their pathogenicity (15q24 duplication [A-D breakpoints], 15q24.2q24.5 deletion and duplication (FBXO22), 17q11.2 duplication (NF1), 17q21.31 duplication (KANSL1) and 22q11.2 distal duplication). Additionally, evidence is presented for the benign nature of some CNVs (15q11.2 duplication (NIPA1) and 2q13 proximal duplication (NPHP1)).
CONCLUSIONS: This is a large-scale systematic review of CNVs associated with neurodevelopment. A synopsis analysing penetrance and pathogenicity is provided for each of the 83 recurrent CNVs.

Fetal alcohol exposure is a growing public health concern. However, ascertaining its true extent remains challenging as maternal self-reports may lack validity. Increasingly, interest has turned to more objective measures of prenatal alcohol use (PAU) of which one, meconium, is recognized as a valuable tool. This review assesses both the international prevalence of PAU obtained using meconium biomarkers in general maternity populations and, when feasible, the level of agreement between meconium biomarkers and self-reported PAU. A systematic literature search for studies reporting the prevalence of PAU, as determined by meconium biomarker testing, was conducted using multiple electronic databases from 1990 to 2023. Seventeen studies were identified for inclusion and evaluated for methodological quality. Using fatty acid ethyl esters (FAEEs) meconium biomarkers, PAU prevalence varied from 2.4% to 44%. Rates based on EtG (ethyl glucuronide) analysis ranged from 0% to 16.3%, and EtS (ethyl sulfate) analysis from 7.8% to 16.7%. Studies were of moderate quality with high heterogeneity. Prevalence rates based on self-report data ranged from 0% to 46.4%. When reported, none of the reviewed studies identified agreement between meconium-based and self-report-based PAU prevalence rates. Using both self-reports to detect early pregnancy alcohol use, and meconium biomarkers to detect the occurrence of alcohol use later in pregnancy, may provide a more complete picture of PAU prevalence. Furthermore, research is warranted to develop stringent guidance on the ascertainment, storage, analysis, and reporting required in this field.

This topical review provides an up-to-date overview of the latest advancements in mind-body therapies in the gynaecological research field. It explores the various mind-body practices and their multifaceted benefits for expectant mothers during the transformative phase of pregnancy, including physical, emotional, and psychological aspects. The research highlights the importance of these practices in promoting maternal and fetal well-being. Prenatal yoga is found to enhance physical health, reduce discomfort, and lower stress and anxiety levels, potentially leading to shorter labour durations. Meditation is revealed to reduce stress and anxiety while nurturing emotional resilience. Prenatal Pilates improves musculoskeletal health and prepares mothers for labour, emphasising controlled movements and breathing techniques. Breathing techniques prove to be helpful for pregnant women in effectively managing pain during labour. Acupressure and reflexology offer non-pharmacological pain relief for common discomforts. Tai Chi improves physical fitness, flexibility, and mental well-being. This brief review, using evidence available from pre-clinical studies in physiological gynaecology literature, demonstrates the role of mind-body practices in enhancing the pregnancy journey, emphasising their integration into daily routines to contribute to overall well-being. By selecting the right practice or combination, expectant mothers can experience an overall better pregnancy.

BACKGROUND: Exposure to poly- and perfluoroalkyl substances (PFAS) may affect infant and childhood health through immunosuppression. However, the findings of epidemiological literature examining relationships between prenatal/childhood PFAS exposure and vaccine response and infection in humans are still inconclusive. The aim of this review was to examine the effects of PFAS exposure on vaccine antibody response and infection in humans.
METHODS: The MEDLINE/Pubmed database was searched for publications until 1 February 2023 to identify human studies on PFAS exposure and human health. Eligible for inclusion studies had to have an epidemiological study design and must have performed logistic regression analyses of gestational or childhood exposure to PFAS against either antibody levels for pediatric vaccines or the occurrence of children\'s infectious diseases. Information on baseline exposure to PFAS (in ng/mL), the age of PFAS exposure (gestational or in years), and the outcome was measured, potentially leading to multiple exposure-outcome comparisons within each study was collected. Percentage change and standard errors of antibody titers and occurrence of infectious diseases per doubling of PFAS exposure were calculated, and a quality assessment of each study was performed.
RESULTS: Seventeen articles were identified matching the inclusion criteria and were included in the meta-analysis. In general, a small decrease in antibody response and some associations between PFAS exposure and childhood infections were observed.
CONCLUSIONS: This meta-analysis summarizes the findings of PFAS effects on infant and childhood immune health. The immunosuppression findings for infections yielded suggestive evidence related to PFAS exposure, particularly PFOS, PFOA, PFHxS, and PFNA but moderate to no evidence regarding antibody titer reduction.
BACKGROUND: The research protocol of this systematic review is registered and accessible at the Open Science Framework ( https://doi.org/10.17605/OSF.IO/5M2VU ).

The prenatal and neonatal periods are two of the most important developmental stages of the human brain. It is therefore crucial to understand normal brain development and how early connections are established during these periods, in order to advance the state of knowledge on altered brain development and eventually identify early brain markers of neurodevelopmental disorders and diseases. In this systematic review (Prospero ID: CRD42024511365), we compiled resting state functional magnetic resonance imaging (fMRI) studies in healthy fetuses and neonates, in order to outline the main characteristics of typical development of the functional brain connectivity during the prenatal and neonatal periods. A systematic search of five databases identified a total of 12 573 articles. Of those, 28 articles met pre-established selection criteria based determined by the authors after surveying and compiling the major limitations reported within the literature. Inclusion criteria were: (1) resting state studies; (2) presentation of original results; (3) use of fMRI with minimum one Tesla; (4) a population ranging from 20 weeks of GA to term birth (around 37-42 weeks of PMA); (5) singleton pregnancy with normal development (absence of any complications known to alter brain development). Exclusion criteria were: (1) preterm studies; (2) post-mortem studies; (3) clinical or pathological studies; (4) twin studies; (5) papers with a sole focus on methodology (i.e. focused on tool and analysis development); (6) volumetric studies; (7) activation map studies; (8) cortical analysis studies; (9) conference papers. A risk of bias assessment was also done to evaluate each article\'s methodological rigor. 1877 participants were included across all the reviewed articles. Results consistently revealed a developmental gradient of increasing functional brain connectivity from posterior to anterior regions and from proximal-to-distal regions. A decrease in local small-world organization shortly after birth was also observed; small-world characteristics were present in fetuses and newborns, but appeared weaker in the latter group. Also, the posterior-to-anterior gradient could be associated with earlier development of the sensorimotor networks in the posterior regions while more complex higher-order networks (e.g. attention-related) mature later in the anterior regions. The main limitations of this systematic review stem from the inherent limitations of functional imaging in fetuses, mainly: unevenly distributed populations and limited sample sizes; fetal movements in the womb and other imaging obstacles; and a large voxel resolution when imaging a small brain. Another limitation specific to this review is the relatively small number of included articles compared to very a large search result, which may have led to relevant articles having been overlooked.

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, originates from a multifaceted interplay of genetic, neurological, and environmental factors. Recent studies have increasingly concentrated on environmental determinants, notably air pollution, and their impact on the risk of developing ADHD. Additionally, previous research has often conflated clinically diagnosed ADHD cases with instances of mere ADHD-like symptoms, a methodology that can introduce bias and obscure the true relationship between environmental factors and ADHD. To address this oversight, our systematic review meticulously investigates the relationship between both prenatal and postnatal exposures to particular air pollutants and strictly clinically diagnosed ADHD. Our comprehensive review encompassed 801 studies from PubMed, Cochrane Library, Web of Science, and Embase databases, out of which eight met our rigorous inclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized to gauge quality and bias. Our review found substantiated the connection between prenatal exposure to PM2.5 and NOx and a heightened risk of ADHD, while exposure to PM10 during the prenatal stage was not associated with ADHD. These findings hint at varied health impacts from different particulate matters and the prospect of gender-specific susceptibilities to such exposures. We also identified an association between postnatal exposure to PM2.5, PM10, and NO2 and an increased ADHD risk, underlining the potential neurodevelopmental harms from early exposure to these pollutants. These relationships, seemingly intricate and potentially dose-dependent, underscore the need for more detailed scrutiny. The unique value of our review is in its detailed exploration of the association between specific air pollution exposures and clinically diagnosed ADHD. Our findings offer much-needed clarity in this complex domain and emphasize the importance of future research to standardize exposure and outcome metrics, probe potential mechanisms, and reduce bias and heterogeneity.

BACKGROUND: This is a systematic review on patient-provider satisfaction in U.S. prenatal care by addressing the following research question: What factors influence patient-provider satisfaction during prenatal care?
METHODS: Thirty six online databases were searched for peer-reviewed research from February to September of 2018 using 10 key terms published in English on U.S. populations between the years 1993-2018 on the topic of provider communication skills and patient satisfaction in the prenatal context. Searches yielded 2563 articles. After duplicates were reviewed and eligibility determined, 32 articles met criteria and were included in the final content analysis. All reported study variables were entered into EXCEL, data reported in each study were analyzed by two people for inter-rater reliability and included in the qualitative content analysis. Two researchers also utilized assessment tools to assess the quality of the articles.
RESULTS: Results indicate the importance of good patient-provider communication, that patients have a need for more information on a plethora of topics, and that Hispanic and African American women reported less satisfaction.
CONCLUSIONS: We recommend that future studies measure potentially significant themes not adequately present in the reviewed studies such as practitioner demographics (e.g. gender, years of experience, or race/ethnicity), mothers under 18 years of age, inclusion of religious minorities, patients with differing immigration statuses, and patients with disabilities.

BACKGROUND: Acute leukemia is the most common pediatric cancer, with an incidence peak at 2-5 years of age. Despite the medical advances improving survival rates, children suffer from significant side effects of treatments as well as its high social and economic impact. The frequent prenatal origin of this developmental disease follows the two-hit carcinogenesis model established in the 70s: a first hit in prenatal life with the creation of genetic fusion lesions or aneuploidy in hematopoietic progenitor/stem cells, and usually a second hit in the pediatric age that converts the preleukemic clone into clinical leukemia. Previous research has mostly focused on postnatal environmental factors triggering the second hit.
CONCLUSIONS: There is scarce evidence on prenatal risk factors associated with the first hit. Mainly retrospective case-control studies suggested several environmental and lifestyle determinants as risk factors. If these associations could be confirmed, interventions focused on modifying prenatal factors might influence the subsequent risk of leukemia during childhood and reveal unexplored research avenues for the future. In this review, we aim to comprehensively summarize the currently available evidence on prenatal risk factors for the development of childhood leukemia. According to the findings of this review, parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Other factors such as socioeconomic status, consumption of caffeinated beverages, and smoking consumption have been suggested with inconclusive evidence. Additionally, investigating the association between prenatal factors and genetic lesions associated with childhood leukemia at birth is crucial. Prospective studies evaluating the link between lifestyle factors and genetic alterations could provide indirect evidence supporting new research avenues for leukemia prevention. Maternal diet and lifestyle factors are modifiable determinants associated with adverse perinatal outcomes that could be also related to preleukemic lesions.
CONCLUSIONS: Parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Dedicating efforts to studying maternal lifestyle during pregnancy and its association with genetic lesions leading to childhood leukemia could lead to novel prevention strategies.

Prenatal vitamin D (PVD) is a vital micronutrient for dental caries (DCs). The association between prenatal vitamin D deficiencies (PVDD) and DCs in children has been conflicting in different reports. This meta-analysis aimed to investigate the association between PVDD and DCs in children for the first time. We searched PubMed, Scopus, Web of Sciences, Embase, and Scholar databases to find relevant studies based on mesh terms from 2000 to October 2023. This study was conducted based on the 2020 version of the PRISMA checklist. Cochran\'s Q and I2 tests were used to evaluate heterogeneity between studies. Egger\'s test was used to evaluate publication bias. The effect size of the association between PVDD and DCs was reported by the odds ratio (OR) at the 95% confidence interval (95% CI).Twelve studies, including 11,021 participants, were reviewed. The pooled prevalence of PVDD was estimated at 4353 (32%). The prevalence of DCs in children of mothers with and without PVDD was 44% and 25%, respectively. PVDD was significantly associated with an increased risk of DCs in children (OR: 1.35, 95% CI (1.22, 1.47), I2 = 86.6%). The association of DCs with PVDD was different based on gestational age groups, children\'s age groups, and vitamin D levels. This meta-analysis showed PVDD can be associated with an increased risk of DCs in children, especially in mothers with prenatal vitamin D levels ≤ 35 nmol/L. Adequate vitamin D levels throughout pregnancy can help prevent DCs in children.