Childhood Growth Trajectories Research Articles

A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1–2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from −0.16 to −0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (−0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.

Growth trajectories of children born preterm and full term with low birth weight to preschool ages: A nationwide study.

Preterm (PT) and full term with low birth weight (FT-LBW) children are at a high-risk of poor growth outcomes. To investigate the growth trajectories of PT and FT-LBW children from birth to preschool ages. This study included 1,150,508 infants (PT, 41,454; FT-LBW, 38,250) who underwent the first three rounds (4-6, 9-12, and 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into Z-scores. Growth data at 2, 4, and 6 years old were measured as outcome variables. The impact of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional-hazards regression analysis. The median birth weights of the PT, FT-LBW, and full term (FT) groups were 2.3, 2.4, and 3.2 kg, respectively. The incidence of short stature (height Z-score < -2 standard deviation score [SDS]) and failure to thrive (FTT) (body mass index (BMI) Z-score < -2 SDS) was the highest in the FT-LBW group, followed by the PT and FT groups. At 4 years old, the incidence rates were 6.0% vs. 5.2% vs. 1.9% for short stature and 4.6% vs. 3.9% vs. 1.7% for FTT. The β estimate of height outcome was lower in both the PT (-0.326 SDS) and FT-LBW (-0.456 SDS) groups. The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group, highlighting the significance of growth monitoring in high-risk populations.

Recent changes in growth trajectories: a population-based cohort study of over 5 million Brazilian children born between 2001 and 2014

There is limited evidence on recent trends in childhood growth trajectories in Low-/middle-income countries. We investigated how age-trajectories for height and Body Mass Index (BMI) have changed among Brazilian children born in two different time periods after2000. We used a population-based cohort (part of the "Cohort of 100-Million Brazilians") created by the linkage of three Brazilian administrative databases: the Cadastro Único of the Federal Government, the National System of Live Births and the National Nutritional and Food Surveillance System. We included longitudinal data on 5,750,214 children who were 3 to <10 years of age and born between 2001 and 2014 (20,209,133 observations). We applied fractional polynomial models with random-effects to estimate mean height and BMI trajectories for children. Compared to children born in 2001-2007, the cohort born in 2008-2014 were on average taller, by a z-score of 0.15 in boys and 0.12 in girls. Their height trajectories shifted upwards, by approximately 1cm in both sexes. Levels of BMI increased little, by a z-score of 0.06 (boys) and 0.04 (girls). Mean BMI trajectories also changed little. However, the prevalence of overweight/obesity increased between cohorts, e.g., from 26.8% to 30% in boys and 23.9%-26.6% in girls aged between 5 and <10 years. An increase of 1cm in mean height of Brazilian children during a short period indicates the improvement in maternal and child health, especially those from low-income families due to the new health and welfare policies in Brazil. Although mean BMI changed little, the prevalence of child overweight/obesity slightly increased and remained high. This work was supported by National Council for Scientific and Technological Development - CNPq; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES; National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre; Society for the Study of Human Biology; Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG; Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Complexo da Saúde do Ministério da Saúde - Decit/SECTICS/MS. The study also used resources from the Centre for Data and Knowledge Integration for Health (CIDACS), which receives funding from the Bill & Melinda Gates Foundation, the Wellcome Trust, the Health Surveillance Secretariat of the Ministry of Health and the Secretariat of Science and Technology of the State of Bahia (SECTI-BA).

Longitudinal Growth Trajectories in Children with Cow’s Milk Allergy: Effects of Elimination Diet and Post-Termination Period

Introduction: The primary dietary approach for managing cow’s milk allergy (CMA) is the elimination diet. We aimed to compare the growth patterns of children with CMA during and after the elimination diet with healthy peers and identify influencing factors. Methods: We compared 74 CMA children with age-matched healthy peers. Anthropometric data were collected during the third month of cow’s milk elimination (CME) diet (T1), 3 months after diet cessation (T2), and after ≥3 months of normal diet (T3). Control group measurements coincided. Nutrient intake was assessed by a 3-day record, and patient laboratory results were noted at T3. Results: CMA children had consistently lower weight-for-age (WFA) and height-for-age (HFA) z-scores than controls. WtHt z-score of patients was lower than those of the healthy group at T2. HC z-scores of patients were lower than those of the healthy group at T0, T2, and T3. At T3, the HFA z-score of the CME group demonstrated a negative correlation with the duration of the elimination diet (p = 0.045). Inadequate intake of energy, vitamins A, E, B1, B6, C, folic acid, magnesium, and iron was significantly higher in CMA children (p < 0.05). T3 WFA z-score correlated positively with fiber, vitamin B1, magnesium, and iron intake (p < 0.05). T3 WtHt showed a positive moderate correlation with energy, protein, vitamin E, vitamin B1, vitamin B2, vitamin B6, calcium, magnesium, phosphor, iron intake (p < 0.05). Conclusions: Post-elimination diet, children with CMA need sustained monitoring and potentially micronutrient supplementation to match healthy peers’ growth.

Ethnoracial disparities in childhood growth trajectories in Brazil: a longitudinal nationwide study of four million children

BackgroundThe literature contains scarce data on inequalities in growth trajectories among children born to mothers of diverse ethnoracial background in the first 5 years of life.ObjectiveWe aimed to investigate child growth according to maternal ethnoracial group using a nationwide Brazilian database.MethodsA population-based retrospective cohort study employed linked data from the CIDACS Birth Cohort and the Brazilian Food and Nutrition Surveillance System (SISVAN). Children born at term, aged 5 years or younger who presented two or more measurements of length/height (cm) and weight (kg) were followed up between 2008 and 2017. Prevalence of stunting, underweight, wasting, and thinness were estimated. Nonlinear mixed effect models were used to estimate childhood growth trajectories, among different maternal ethnoracial groups (White, Asian descent, Black, Pardo, and Indigenous), using the raw measures of weight (kg) and height (cm) and the length/height-for-age (L/HAZ) and weight-for-age z-scores (WAZ). The analyses were also adjusted for mother’s age, educational level, and marital status.ResultsA total of 4,090,271 children were included in the study. Children of Indigenous mothers exhibited higher rates of stunting (26.74%) and underweight (5.90%). Wasting and thinness were more prevalent among children of Pardo, Asian, Black, and Indigenous mothers than those of White mothers. Regarding children’s weight (kg) and length/height (cm), those of Indigenous, Pardo, Black, and Asian descent mothers were on average shorter and weighted less than White ones. Regarding WAZ and L/HAZ growth trajectories, a sharp decline in average z-scores was evidenced in the first weeks of life, followed by a period of recovery. Over time, z-scores for most of the subgroups analyzed trended below zero. Children of mother in greater social vulnerability showed less favorable growth.ConclusionWe observed racial disparities in nutritional status and childhood growth trajectories, with children of Indigenous mothers presenting less favorable outcomes compared to their White counterparts. The strengthening of policies aimed at protecting Indigenous children should be urgently undertaken to address systematic ethnoracial health inequalities.

Development of disease-specific growth charts for Korean children with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth syndrome. Despite its distinctive growth pattern, the detailed growth trajectories of children with BWS remain largely unknown. We retrospectively analyzed 413 anthropometric measurements over an average of 4.4 years of follow-up in 51 children with BWS. We constructed sex-specific percentile curves for height, weight, and head circumference using a generalized additive model for location, scale, and shape. Males with BWS exhibited greater height at all ages evaluated, weight before the age of 10, and head circumference before the age of 9 than those of the general population. Females with BWS showed greater height before the age of 7, weight before the age of 4.5, and head circumference before the age of 7 than those of the general population. At the latest follow-up visit at a mean 8.4 years of age, bone age was significantly higher than chronological age. Compared to paternal uniparental disomy (pUPD), males with imprinting center region 2-loss of methylation (IC2-LOM) had higher standard deviation score (SDS) for height and weight, while females with IC2-LOM showed larger SDS for head circumference. These disease-specific growth charts can serve as valuable tools for clinical monitoring of children with BWS.

Hokkaido birth cohort study in Japan on the growth trajectory of children born with low birth weight until 7 years of age

BackgroundLow birth weight (LBW) is a significant global health concern with potential health risks and developmental implications for infants. Catch-up growth, an accelerated growth following an inhibition period, may partially compensate for growth deficits in LBW children. AimsThis study investigated the prevalence of LBW and catch-up growth in height, weight, and body mass index (BMI) among LBW children in Japan, identified factors associated with LBW, and explored the potential for catch-up growth at different ages up to seven years. Study design and subjectsThe Hokkaido birth cohort study included 20,926 pregnant Japanese women recruited during their first trimester from 37 hospitals and clinics. Follow-up assessments were conducted in children up to seven years of age, tracking LBW children's growth and development using the Maternal and Child Health Handbook, and providing valuable insights into catch-up growth patterns. Outcome measuresLBW was defined as a neonatal birth weight of <2500 g. The primary outcomes were catch-up growth in height, weight, and BMI at different ages. Z-scores were calculated to assess growth parameters with catch-up growth, defined as a change in z-score (> 0.67) between two time points. Results and conclusionsA LBW was prevalent in 7.6 % of the cohort, which was lower than that reported in other Japanese studies. Among LBW children, 19.3 % achieved catch-up growth in height by age seven, and 10.6 % in weight. Catch-up growth in LBW children could partially offset these deficits. Further research will help understand the long-term outcomes and inform interventions for healthy development.

Determinants of Anishinabeck infant and early childhood growth trajectories in Northwestern Ontario, Canada: a cohort study

BackgroundThe Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories.MethodsWe recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes.ResultsWAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver’s BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34).ConclusionsThis work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to twoyears and to identify the critical exposure periods. A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first twoyears, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033kb).

Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE (95% CI: 1.05, 1.35); RRR for (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the ; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

EP15.01: Child growth trajectory of discordant twin up to seven years of age

EP15.01: Child growth trajectory of discordant twin up to seven years of age

Late preterm birth and growth trajectories during childhood: a linked retrospective cohort study

BackgroundEvidence suggests that accelerated postnatal growth in children is detrimental for adult cardiovascular health. It is unclear whether children born late preterm (34–36 weeks) compared to full term (≥ 39 weeks), have different growth trajectories. Our objective was to evaluate the association between gestational age groups and growth trajectories of children born between 2006–2014 and followed to 2021 in Ontario, Canada.MethodsWe conducted a retrospective cohort study of children from singleton births in TARGet Kids! primary care network with repeated measures of weight and height/length from birth to 14 years, who were linked to health administrative databases. Piecewise linear mixed models were used to model weight (kg/month) and height (cm/month) trajectories with knots at 3, 12, and 84 months. Analyses were conducted based on chronological age.ResultsThere were 4423 children included with a mean of 11 weight and height measures per child. The mean age at the last visit was 5.9 years (Standard Deviation: 3.1). Generally, the more preterm, the lower the mean value of weight and height until early adolescence. Differences in mean weight and height for very/moderate preterm and late preterm compared to full term were evident until 12 months of age. Weight trajectories were similar between children born late preterm and full term with small differences from 84–168 months (mean difference (MD) -0.04 kg/month, 95% CI -0.06, -0.03). Children born late preterm had faster height gain from 0–3 months (MD 0.70 cm/month, 95% CI 0.42, 0.97) and 3–12 months (MD 0.17 cm/month, 95% CI 0.11, 0.22).ConclusionsCompared to full term, children born late preterm had lower average weight and height from birth to 14 years, had a slightly slower rate of weight gain after 84 months and a faster rate of height gain from 0–12 months. Follow-up is needed to determine if growth differences are associated with long-term disease risk.

Timing of gestational diabetes diagnosis, gestational weight gains and offspring growth trajectory: a prospective birth cohort study

BackgroundThe evidence on the associations of the timing of maternal gestational diabetes mellitus (GDM) with the comprehensive growth trajectory from perinatal to early childhood in offspring is limited. The potential mechanism remains elusive. Our aim is to estimate the associations of the timing of GDM diagnosis and gestational weight gains (GWG) with the growth trajectory of children from perinatal to early childhood.MethodsA total of 7609 participants are included from the Maternal & Infants Health in Hefei cohort study. Primary predictors were the timing of maternal GDM diagnosis and GWG during pregnancy. The main outcomes included fetal ultrasonic measurements, birth size as well as BMI peak indicators during infancy within 48 months.ResultsGDM diagnosed before 26 weeks was associated with increased risks of overgrowth for fetal abdominal circumference (OR 1.19, 95% CI 1.04–1.36) and birth weight (OR 1.51, 95% CI 1.19–1.91) when compared with unexposed. GDM diagnosis < 26 weeks was related to the higher BMI peak (β 0.16, 95%CI 0.03–0.28) within 48 months. The significantly additive impacts of maternal early GDM diagnosis and excessive gestational weight gains (EGWG) on offspring overgrowth were observed. Women in GDM < 26 weeks with early EGWG group had higher levels of hsCRP compared with GDM > 26 weeks (P < 0.001).ConclusionsExposure to maternal GDM diagnosed before 26 weeks with early EGWG could lead to shifts and/or disruptions from the typical growth trajectory from perinatal to early childhood in offspring.

The Effects of Adenotonsillectomy for Obstructive Sleep Apnea on Growth Trajectory in Children With Obesity.

To analyze the growth trajectory of children with obesity before and after adenotonsillectomy (T&A). We hypothesize that T&A will not affect the growth trajectory but children in a multidisciplinary weight management program (MWMP) will have a healthier growth trajectory. Retrospective review. Tertiary Children's Hospital. Body mass index (BMI) trajectories of nonsyndromic children with obesity and obstructive sleep apnea (OSA) who underwent T&A were analyzed. A linear mixed effects model was fit to the BMI expressed as a percentage of the 95th percentile (%BMIp95 ) data. Covariates included demographic variables, pre- and postoperative participation in an MWMP, baseline obesity class, and time. We explored clinically meaningful interactions. BMI slope estimates before and after surgery were calculated and compared for baseline obesity classification and postoperative MWMP visits. A total of 177 patients, 58% male with a mean age of 9.7 years at the time of surgery, were studied. Higher baseline obesity class (II and III), time, the interaction between obesity class III and elapsed time relative to surgical date, and the interaction between obesity class III and the postsurgical period were all significantly associated with the outcome of %BMIp95 (P < .05). There was a significantly higher %BMIp95 trajectory following surgery in patients with baseline obesity class III who did not have any postoperative MWMP visits (P < .001). Preoperative obesity visits, however, were not significantly associated with postoperative growth. The association between T&A and weight trajectory depends upon obesity class and participation in a MWMP. Coordinated care of children with obesity between otolaryngologists and an MWMP may improve OSA and obesity outcomes. The level of evidence: 3.

First-year growth trajectory and early nutritional requirements for optimal growth in infants with congenital diaphragmatic hernia: a retrospective cohort study

ObjectiveTo describe the growth trajectory of children with congenital diaphragmatic hernia (CDH) during the first year, to assess the risk factors for growth failure (GF) at 1 year and to...

Sex-specific effects of organophosphate ester exposure on child growth trajectories in the first two years

The connections between urinary organophosphate ester (OPE) metabolites and child growth have been identified in prior research, but there is currently a dearth of epidemiological evidence regarding the sex-specific impact of OPEs on child growth trajectories. This study enrolled 804 maternal–child pairs, and five OPE congeners were quantified in maternal serum during pregnancy. In this study, the impact of prenatal OPE exposure on child growth trajectories was assessed using linear mixed-effect models and a group-based trajectory model (GBTM), with consideration given to sex-specific effects. Fetuses were frequently exposed to OPEs in utero, and tris(2-butoxyethel) phosphate (TBEP) exhibited the highest concentration levels in maternal serum. Among male children, an increase of 2.72 ng/g lipid in TBEP concentration was associated with a 0.11-unit increase in head circumference-for-age z-score (HCAZ), and the effect was mainly concentrated at 1 and 2 months of age. Among female children, an increase of 2.72 ng/g lipid in tris(2-chloro-1-(chloromethyl) ethyl) phosphate (TDCPP) concentration was associated with a 0.15-unit increase in length-for-age z-score (LAZ) and a 0.14-unit increase in weight-for-age z-score (WAZ), and the effects were mainly concentrated at 9 months of age. For HCAZ trajectories, higher prenatal TBEP exposure was associated with higher odds for the fast growth group in male children. For the LAZ and WAZ trajectories, higher prenatal TDCPP exposure was associated with higher odds for the fast growth group in female children. The trajectory analysis approach provided insight into the complex associations between OPE exposure and child growth.

Prenatal exposure to phthalates and child growth trajectories in the first 24 months of life

BackgroundPhthalates are a class of environmental chemicals with endocrine-disrupting properties. Prenatal phthalate exposure has been associated with adverse developmental outcomes in childhood. However, data assessing the effects of prenatal phthalate exposure on postnatal infant growth trajectories are sparse. ObjectivesTo evaluate the associations of prenatal phthalate exposure with child growth trajectories from birth to 24 months old. MethodsWithin a Chinese birth cohort study, 1051 mother-offspring pairs were included. Seven phthalate metabolites were quantified in maternal urine collected between weeks 33 and 39 of gestation. The trajectories for weight-for-age z-score (WAZ), length-for-age z-score (LAZ), weight-for-length z-score (WLZ) and head-circumference-for-age z-score (HCZ) were determined by group-based trajectory modeling (GBTM). Multinomial logistic regression and the weighted quantile sum approach (WQS) were used to investigate the association between individual and phthalate mixture exposure and the growth trajectories of four anthropometric metrics. ResultsFive trajectory groups were identified for each anthropometric measure using GBTM. Higher prenatal exposure to several phthalate metabolites (MEHP, MEHHP, MEOHP, MECCP, summed DEHP metabolites, as well as MBP) was associated with child growth trajectories, especially for WAZ and LAZ in the first 24 months of life. The associations were further confirmed by a mixture analysis of phthalate metabolites and a sex-specific effect was observed in the WAZ and LAZ trajectories. ConclusionPrenatal phthalate exposure had heterogeneous associations with postnatal growth trajectories. More studies are warranted to confirm and elucidate the meaning of our findings.

A novel systematic pipeline for increased predictability and explainability of growth patterns in children using trajectory features

ObjectiveLongitudinal patterns of growth in early childhood are associated with health conditions throughout life. Knowledge of such patterns and the ability to predict them can lead to better prevention and improved health promotion in adulthood. However, growth analyses are characterized by significant variability, and pattern detection is affected by the method applied. Moreover, pattern labelling is typically performed based on ad hoc methods, such as visualizations or clinical experience. Here, we propose a novel pipeline using features extracted from growth trajectories using mathematical, statistical and machine-learning approaches to predict growth patterns and label them in a systematic and unequivocal manner. Methods: We extracted mathematical and clinical features from 9577 children growth trajectories embedded with machine-learning predictions of the growth patterns. We experimented with two sets of features (CAnonical Time-series Characteristics and trajectory features specific to growth), developmental periods and six machine-learning classifiers. Clinical experts provided labels for the detected patterns and decision rules were created to associate the features with the labelled patterns. The predictive capacity of the extracted features was validated on two heterogenous populations (The Applied Research Group for Kids and the 2004 Pelotas Birth Cohort, based in Canada and Brazil, respectively). Results: Features predictive ability measured by accuracy and F1 score was ≥ 80% and ≥ 0.76 respectively in both cohorts. A small number of features (n = 74) was sufficient to distinguish between growth patterns in both cohorts. Slope, intercept of the trajectory, age at peak value, start value and change of the growth measure were among the top identified features. Conclusion: Growth features can be reliably used as predictors of growth patterns and provide an unbiased understanding of growth patterns. They can be used as tool to reduce the effort to repeat analysis and variability concerning anthropometric measures, time points and analytical methods, in the context of the same or similar populations.

Early life growth and developmental trajectory in children with biliary atresia undergoing primary liver transplantation.

To clarify the early growth and developmental characteristics of children with biliary atresia (BA) undergoing primary liver transplantation (pLT). A prospective cohort study, which specifically focused on BA-pLT children, was conducted after the diagnosis of BA by following the children at the time of pLT and 1, 3, 5, 7 months and 1 year after pLT for growth and developmental monitoring. The growth parameters were calculated according to the WHO standard, and the developmental status was assessed using Denver Developmental Screening Tests. A total of 48 BA children who received pLT at the age of 5.00 ± 0.94 months were analyzed. The weight-for-age Z-value (ZW) and length-for-age Z-value (ZL) were higher than the head circumference-for-age Z-value (ZHC) at pLT (P = 0.002 and 0.02), but they were all lower than the WHO growth standard (Z = 0) (P < 0.001). The ZW and ZHC decreased first and then returned to the population level at 1 year after pLT, while the ZL only returned to the preoperative status and was lower than the ZW and ZHC (P < 0.001). Developmental screening showed that 35% (17/48) of the children were defined as suspicious and 15% (7/48) were abnormal at 1-4 months after pLT, the most likely time to be suspected of developmental delay. At 1 year after pLT, gross motor skill delay still existed (12/45, 27%), and language skill delay began to appear (4/45, 9%). BA-pLT children suffer from growth and developmental problems. Low ZHC is the main growth problem before pLT, while low ZL is the problem after pLT. Developmental delays are significant after pLT, especially in motor and language skills. The current study suggested that further studies are warranted to clarify the long-term growth and developmental outcomes of BA-pLT children, to compare them with children undergoing the Kasai procedure and to explore their influencing factors and possible mechanisms.

Deviation From Normative Whole Brain and Deep Gray Matter Growth in Children With MOGAD, MS, and Monophasic Seronegative Demyelination.

Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination. We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized z scores for brain volume using a normative dataset of 813 brain MRI scans obtained from typically developing children and used mixed-effect models to assess potential deviation from brain growth trajectories. We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed (p < 0.001) age-expected and sex-expected growth of thalamus, caudate, and globus pallidus, normalized for the whole brain volume. Divergence from expected growth was particularly pronounced in the first year postonset and was detected even in children with monophasic MOGAD. Thalamic volume abnormalities were less pronounced in children with MOGAD compared with those in children with MS. The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time.