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The identification of tumor-specific molecular dependencies is essential for the development of effective cancer therapies. Genetic and chemical perturbations are powerful tools for discovering these dependencies. Even though chemical perturbations can be applied to primary cancer samples at large scale, the interpretation of experiment outcomes is often complicated by the fact that one chemical compound can affect multiple proteins. To overcome this challenge, Batzilla et al. (PLoS Comput Biol 18(8): e1010438, 2022) proposed DepInfeR, a regularized multi-response regression model designed to identify and estimate specific molecular dependencies of individual cancers from their ex-vivo drug sensitivity profiles. Inspired by their work, we propose a Bayesian extension to DepInfeR. Our proposed approach offers several advantages over DepInfeR, including e.g. the ability to handle missing values in both protein-drug affinity and drug sensitivity profiles without the need for data pre-processing steps such as imputation. Moreover, our approach uses Gaussian Processes to capture more complex molecular dependency structures, and provides probabilistic statements about whether a protein in the protein-drug affinity profiles is informative to the drug sensitivity profiles. Simulation studies demonstrate that our proposed approach achieves better prediction accuracy, and is able to discover unreported dependency structures.
\n \n\n \n \nLarge loop excision of the transformation zone is an extremely common procedure routinely carried out in a gynaecology or colposcopy outpatient setting under local anaesthetic. Here, we present a rare case resulting in emergency hysterectomy. A healthy para 3, who had been diagnosed with microscopic cancer of the cervix, attended colposcopy for repeat excision. The colposcopy revealed a normal cervix, and diathermy loop excision was performed. During the procedure, heavy bleeding from the anterior cutting edge was noted. Despite the best attempts to manage the haemorrhage conservatively in outpatients, the bleeding persisted, and the patient was transferred to theatres. Examination under anaesthesia revealed an injury to the descending branch of the uterine artery, and emergency hysterectomy was performed. Immediate recognition of an extremely rare complication, fast decision-making and a cross-disciplinary approach led to a satisfactory outcome.
\n \n\n \n \nBackground: INTERBIO-21 st is Phase II of the INTERGROWTH-21 st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21 st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.
\n \n\n \n \nAbstractIt is unclear whether early child development is, like skeletal growth, similar across diverse regions\u00a0with adequate health and nutrition. We prospectively assessed 1307\u00a0healthy, well-nourished 2-year-old children of educated mothers, enrolled in early pregnancy from urban areas without major socioeconomic or environmental constraints,\u00a0in Brazil, India, Italy, Kenya and UK. We used a specially developed psychometric tool, WHO motor milestones and visual tests. Similarities across sites were measured using variance components analysis and standardised site differences (SSD). In 14 of the 16 domains, the percentage of total variance explained by between-site differences ranged from 1.3% (cognitive score) to 9.2% (behaviour score). Of the 80 SSD comparisons, only six were >\u00b10.50 units of the pooled SD for the corresponding item. The sequence and timing of attainment of neurodevelopmental milestones and associated behaviours in early childhood are, therefore, likely innate and universal, as\u00a0long as nutritional and health needs are met.
\n \n\n \n \nComplex perinatal syndromes (CPS) affecting pregnancy and childhood, such as preterm birth, and intra- and extra-uterine growth restriction, have multiple, diverse contexts of complexity and interaction that determine the short- and long-term growth, health and development of all human beings. Early in life, genetically-guided somatic and cerebral development occurs alongside a psychism \u201cin statu nascendi,\u201d with the neural structures subjected to the effects of the intra- and extra-uterine environments in preparation for optimal postnatal functioning. Different trajectories of fetal cranial and abdominal growth have been identified before 25 weeks\u2019 gestation, tracking differential growth and neurodevelopment at 2 years of age. Similarly, critical time-windows exist in the first 5\u20138 months of postnatal life because of interactions between the newborn and their environment, mother/care-givers and feeding practices. Understanding these complex relational processes requires abandoning classical, linear and mechanistic interpretations that are placed in rigid, artificial biological silos. Instead, we need to conduct longitudinal, interdisciplinary research and integrate the resulting new knowledge into clinical practice. An ecological-systemic approach is required to understand early human growth and development, based on a dynamic multidimensional process from the molecular or genomic level to the socio-economic-environmental context. For this, we need theoretical and methodological tools that permit a global understanding of CPS, delineating temporal trajectories and their conditioning factors, updated by the incorporation of new scientific discoveries. The potential to optimize human growth and development across chronological age and geographical locations \u2013 by implementing interventions or \u201ctreatments\u201d during periods of greatest instability or vulnerability \u2013 should be recognized. Hence, it is imperative to take a holistic view of reproductive and perinatal issues, acknowledging at all levels the complexity and interactions of CPS and their sensitive periods, laying the foundations for further improvements in growth and development of populations, to maximize global human potential. We discuss here conceptual issues that should be considered for the development and implementation of such a strategy aimed at addressing the perinatal health problems of the new millenium.
\n \n\n \n \nBACKGROUND: Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH). METHODS: MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000\u00a0IU/day cholecalciferol from 14\u00a0weeks' gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500\u00a0ml estimated blood loss) were determined from medical records. RESULTS: A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P\u00a0=\u00a00.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P\u00a0=\u00a00.054) overall], but similar when stratified by delivery mode. CONCLUSIONS: Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD.
\n \n\n \n \nBACKGROUND: In recent years, the prevalence of non-communicable diseases (NCDs) has escalated. Evidence suggests that there are strong associations between nutrition in early life and the risk of disease in adulthood. This manuscript describes the study protocol of the First United Arab Emirates National Representative Birth Cohort Study (UAE-BCS), with the objective of investigating nutrition and lifestyle factors in the first 1,000 days of life. The main aims of the study are (1) to address critical issues relating to mother and child nutrition and their effect on growth and development, (2) to profile maternal nutrition, child growth, health, and development outcomes in early life, and (3) to study the associations between these factors among the Emirati population in the UAE. METHODS/DESIGN: In this study, a multidisciplinary team of researchers was established including credible researchers from the UAE, Lebanon, Australia, and the United Kingdom to launch the First United Arab Emirates 3-year birth cohort study. We aim to recruit 260 pregnant Emirati women within their first trimester, which is defined by the study as from 8 to 12 weeks pregnant, from obstetrics and gynecology clinics in the UAE. Participants will be recruited via face-to-face interviews and will receive a total of 11 visits with 1 visit in each trimester of pregnancy and 8 visits after delivery. Maternal data collection includes, socio-demographic and lifestyle factors, dietary intake, anthropometric measurements, physical activity, maternal psychological state, and blood samples for biochemical analysis. Post-partum, visits will take place when the child is 0.5, 4, 6, 9, 12, 18, and 24 months old, with data collection including infant anthropometric measurements, young child feeding practices, dietary intake, supplement use and the eating environment at home, as well as all maternal data collection described above, apart from blood samples. Additional data collection for the child includes early child developmental assessments taking place at three timepoints: (1) within 2 weeks of birth, (2) at 10-14 months and (3) at 22-26 months of age. Early child developmental assessments for the infant include vision, hearing, cognition, motor skills, social-emotional reactivity, neurodevelopmental, and sleep assessments. DISCUSSION: The United Arab Emirates Birth Cohort study protocol provides a standardized model of data collection methods for collaboration among the multisectoral teams within the United Arab Emirates to enrich the quality and research efficiency in early nutrition, thereby enhancing the health of mothers, infants, and children.
\n \n\n \n \nAbstractObjectivesA previous individual participant data meta\u2010analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire\u20109. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum.MethodsData accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics.ResultsAmong fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased.ConclusionDifferent interviews may not classify major depression equivalently.
\n \n\n \n \nIMPORTANCE: Effective screening strategies for early-onset neonatal sepsis (EONS) have the potential to reduce high volume parenteral antibiotics (PAb) usage in neonates. OBJECTIVE: To compare management decisions for EONS, between CG149 National Institute for Health and Care Excellence (NICE) guidelines and those projected through the virtual application of the Kaiser Permanente sepsis risk calculator (SRC) in a level 2 neonatal unit at a district general hospital (DGH). METHODS: Hospital records were reviewed for maternal and neonatal risk factors for EONS, neonatal clinical examination findings, and microbial culture results for all neonates born at \u226534 weeks' gestation between February and July 2019, who were (1) managed according to CG149-NICE guidelines or (2) received PAb within 72 h following birth at a DGH in Winchester, UK. SRC projections were obtained using its virtual risk estimator. RESULTS: Sixty infants received PAb within the first 72 h of birth during the study period. Of these, 19 (31.7%) met SRC criteria for antibiotics; 20 (33.3%) met the criteria for enhanced observations and none had culture-proven sepsis. Based on SRC projections, neonates with '\u22651 NICE clinical indicator and \u22651 risk factor' were most likely to have a sepsis risk score (SRS) >3. Birth below 37 weeks' gestation (risk ratio\u00a0[RR]\u00a0= 2.31, 95% confidence interval [CI]: 1.02-5.22) and prolonged rupture of membranes (RR\u00a0= 3.14, 95% CI: 1.16-8.48) increased the risk of an SRS >3. INTERPRETATION: Screening for EONS on the SRC could potentially reduce PAb usage by 68% in term and near-term neonates in level 2 neonatal units.
\n \n\n \n \nBACKGROUND: Maternal nutrition in preconception and early pregnancy influences fetal growth. Evidence for effects of prenatal maternal nutrition on early child development (ECD) in low-income and middle-income countries is limited. OBJECTIVES: To examine impact of maternal nutrition supplementation initiated prior to or during pregnancy on ECD, and to examine potential association of postnatal growth with ECD domains. DESIGN: Secondary analysis regarding the offspring of participants of a maternal multicountry, individually randomised trial. SETTING: Rural Democratic Republic of the Congo, Guatemala, India and Pakistan. PARTICIPANTS: 667 offspring of Women First trial participants, aged 24 months. INTERVENTION: Maternal lipid-based nutrient supplement initiated preconceptionally (arm 1, n=217), 12 weeks gestation (arm 2, n=230) or not (arm 3, n=220); intervention stopped at delivery. MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) cognitive, language, gross motor, fine motor, positive and negative behaviour scores; visual acuity and contrast sensitivity scores and auditory evoked response potentials (ERP). Anthropometric z-scores, family care indicators (FCI) and sociodemographic variables were examined as covariates. RESULTS: No significant differences were detected among the intervention arms for any INTER-NDA scores across domains, vision scores or ERP potentials. After adjusting for covariates, length-for-age z-score at 24 months (LAZ24), socio-economic status, maternal education and FCI significantly predicted vision and INTER-NDA scores (R2=0.11-0.38, p<0.01). CONCLUSIONS: Prenatal maternal nutrition supplementation was not associated with any neurodevelopmental outcomes at age 2 years. Maternal education, family environment and LAZ24 predicted ECD. Interventions addressing multiple components of the nurturing care model may offer greatest impact on children's developmental potential. TRIAL REGISTRATION NUMBER: NCT01883193.
\n \n\n \n \nAbstractObjectiveTo document the prevalence of self\u2010reported postpartum hemorrhage (PPH) in Ga East, Accra, Ghana, and examine the demographic, biological, and social risk factors for PPH.MethodsThe present study was a cross\u2010sectional secondary analysis of data collected during 2010\u20132012 from the Ghana Essential Health Interventions Program, a quasi\u2010experimental interventional study surveying households in the urban Ga East Municipal District. The analysis included data from randomly selected parous women of childbearing age (15\u201349\u00a0years), excluding those with a history of abortion (spontaneous or induced) or stillbirth. The \u03c72 test and logistic regression were used to identify significant risk factors for self\u2010reported PPH.ResultsThe current analysis included 2136 women. Self\u2010reported PPH was recorded for 95 (4.4%) participants. The maternal age at delivery, the duration of labor, and the number of skilled delivery providers were significantly associated with self\u2010reported PPH. Prolonged labor (odds ratio 3.70, 95% confidence interval 2.27\u20135.94; P<0.001) and maternal age (odds ratio 0.96, 95% confidence interval 0.94\u20130.99; P=0.020) were predictors of self\u2010reported PPH.ConclusionProlonged labor and younger maternal age were related to a higher burden of reported PPH. These findings were congruent with global and regional data on the prevalence and risk factors for objectively measured PPH and could help focus intervention strategies to high\u2010risk groups, particularly in resource\u2010limited settings.
\n \n\n \n \nThis article extends the research focusing on the early origins of psychopathology into the prenatal period, by exploring the association between maternal prenatal depression and offspring (fetal and infant) neurobehavior. The sample is recruited from a rural population in South India where women in the third trimester of pregnancy were assessed for depression and the heart rate responses of their fetuses to extrinsically applied vibroacoustic stimuli were studied. At 2 months postbirth, infant temperament and cortisol responsivity to immunization were assessed. The association between maternal prenatal depression and fetal responsivity to vibroacoustic stimulation, and infant responsivity to immunization, was U shaped with higher levels of responsivity noted in the offspring of mothers with very high and very low depression scores, and lower levels noted in the offspring of mothers with moderate depression scores. Maternal prenatal depression was not associated with infant temperament. The findings highlight the importance of environmental influences in the developmental origins of neurobehavior, suggesting that such differences, not evident at baseline, may emerge upon exposure to stressors. The study also emphasizes the need for further investigation in low- and middle-income contexts by providing preliminary evidence of the differing patterns of association observed between high- and low-income populations.
\n \n\n \n \nMany young children in low- and middle-income countries (LMICs) are at risk of developmental delays. Early child development (ECD) interventions have been shown to improve outcomes, but few interventions have targeted culturally normative violence such as corporal punishment (CP). We partnered with an existing community-based ECD organization in the LMIC of Grenada to implement a parallel controlled-trial single-blind responsive caregiving intervention that educates parents about the developing brain and teaches alternatives to corporal punishment while building parental self-regulation skills and strengthening social-emotional connections between parent and child. Parents and primary caregivers with children under age two were eligible. Allocation to the intervention and waitlist control arms was unblinded and determined by recruitment into the program. Neurodevelopment was assessed by blinded testers when each child turned age two. Primary comparison consisted of neurodevelopmental scores between the intervention and waitlist control groups (Clinicaltrials.gov registration # NCT04697134). Secondary comparison consisted of changes in maternal mental health, home environment, and attitudes towards CP. Children in the intervention group (n = 153) had significantly higher scores than children in the control group (n = 151) on measures of cognition (p = .022), fine motor (p < .0001), gross motor (p = .015), and language development (p = .013). No difference in secondary outcomes, including CP, was detected.
\n \n\n \n \nOBJECTIVE: Zika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls. DESIGN: Cohort study. SETTING: Public health centres in Grenada, West Indies. PATIENTS: 384 mother-child pairs were enrolled during a period of active ZIKV transmission (April 2016-March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child's exposure status. RESULTS: A total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays. CONCLUSIONS: Overall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.
\n \n\n \n \nObjective: At the broadest level, self-regulation (SR) refers to a range of separate, but interrelated, processes (e.g., working memory, inhibition, and emotion regulation) central for the regulation of cognition, emotion, and behavior that contribute to a plethora of health and mental health outcomes. SR skills develop rapidly in early childhood, but their neurobiological underpinnings are not yet well understood. The amygdala is one key structure in negative emotion generation that may disrupt SR. In the current study, we investigated the associations between neonatal amygdala volumes and mother-reported and observed child SR during the first 3 years of life. We expected that larger neonatal amygdala volumes would be related to poorer SR in children. Method: We measured amygdala volumes from magnetic resonance imaging (MRI) performed at age M = 3.7 \u00b1 1.0. We examined the associations between the amygdala volumes corrected for intracranial volume (ICV) and (a) parent-reported indicators of SR at 6, 12, and 24 months (N = 102) and (b) observed task-based indicators of SR (working memory and inhibitory control) at 30 months of age in a smaller subset of participants (N = 80). Results: Bilateral neonatal amygdala volumes predicted poorer working memory at 30 months in girls, whereas no association was detected between amygdalae and inhibitory control or parent-reported SR. The left amygdala by sex interaction survived correction for multiple comparisons. Conclusions: Neonatal amygdala volume is associated with working memory, particularly among girls, and the association is observed earlier than in prior studies. Moreover, our findings suggest that the neural correlates for parent-reported, compared to observed early life SR, may differ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
\n \n\n \n \nMaternal infection with Zika virus (ZIKV) is associated with a distinct pattern of birth defects, known as congenital Zika syndrome (CZS). In ZIKV-exposed children without CZS, it is often unclear whether they were protected from in utero infection and neurotropism. Early neurodevelopmental assessment is essential for detecting neurodevelopmental delays (NDDs) and prioritizing at-risk children for early intervention. We compared neurodevelopmental outcomes between ZIKV-exposed and unexposed children at 1, 3 and 4 years to assess exposure-associated NDD risk. A total of 384 mother-child dyads were enrolled during a period of active ZIKV transmission (2016-2017) in Grenada, West Indies. Exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. Neurodevelopment was assessed using the Oxford Neurodevelopment Assessment, the NEPSY\u00ae Second Edition and Cardiff Vision Tests, at 12 (n = 66), 36 (n = 58) and 48 (n = 59) months, respectively. There were no differences in NDD rates or vision scores between ZIKV-exposed and unexposed children. Rates of microcephaly at birth (0.88% vs. 0.83%, p = 0.81), and childhood stunting and wasting did not differ between groups. Our results show that Grenadian ZIKV-exposed children, the majority of whom were without microcephaly, had similar neurodevelopmental outcomes to unexposed controls up to at least an age of 4 years.
\n \n\n \n \nBACKGROUND: Over 250 million children under 5\u2009years, globally, are at risk of developmental delay. Interventions during the first 2\u2009years of life have enduring positive effects if children at risk are identified, using standardized assessments, within this window. However, identifying developmental delay during infancy is challenging and there are limited infant development assessments suitable for use in low- and middle-income (LMIC) settings. Here, we describe a new tool, the Oxford Neurodevelopment Assessment (OX-NDA), measuring cognition, language, motor, and behaviour, outcomes in 1-year-old children. We present the results of its evaluation against the Bayley Scales of Infant Development IIIrd edition (BSID-III) and its psychometric properties. METHODS: Sixteen international tools measuring infant development were analysed to inform the OX-NDA's construction. Its agreement with the BSID-III, for cognitive, motor and language domains, was evaluated using intra-class correlations (ICCs, for absolute agreement), Bland-Altman analyses (for bias and limits of agreement), and sensitivity and specificity analyses (for accuracy) in 104 Brazilian children, aged 12\u2009months (SD 8.4\u2009days), recruited from the 2015 Pelotas Birth Cohort Study. Behaviour was not evaluated, as the BSID-III's adaptive behaviour scale was not included in the cohort's protocol. Cohen's kappas and Cronbach's alphas were calculated to determine the OX-NDA's reliability and internal consistency respectively. RESULTS: Agreement was moderate for cognition and motor outcomes (ICCs 0.63 and 0.68, p\u2009
\n \n\n \n \nOBJECTIVE: We examined associations between fat free mass (FFM) and fat mass (FM) accretion during the first 1000 days of life and neurodevelopment in term-born, low-risk infants from Karachi, Pakistan. DESIGN: Prospective, observational study nested within the larger Multi-Center Body Composition Reference Study. FFM, FM, and fat% were estimated using measured deuterium dilution method. Neurodevelopmental outcomes were assessed at 24 months on the INTER-NDA (INTERGROWTH-21st Project Neurodevelopment Assessment) (n\u2009=\u2009132). RESULTS: Children with gross motor delays had significantly lower FFM at 18 months (8.01\u2009\u00b1\u20090.97\u2009kg vs. 7.55\u2009\u00b1\u20090.20\u2009kg). Children with positive and negative behavior problems had significantly higher fat% at 24 months (20.62\u2009\u00b1\u20094.30% vs. 18.23\u2009\u00b1\u20095.46%) and 20.89\u2009\u00b1\u20094.24% vs. 18.54\u2009\u00b1\u20095.38%). No associations remained significant after adjusting for covariates. Trajectory modeling showed that between 12 and 18 months, negative behavior scores changed by 13.8 points for every standard deviation change in fat accretion. CONCLUSIONS: Our findings highlight the importance of balancing neurodevelopment and metabolic risk when designing nutritional interventions for young children.
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