Mental Development Index Scores Research Articles

A prospective birth cohort study on the association between gestational blood pressure and neurodevelopment in 2-year-old children

Objective: To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children. Methods: Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index. Results: The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m² and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters. Conclusion: There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.

Association between maternal haemoglobin status during pregnancy and children’s mental and psychomotor development at 18 months of age: Evidence from rural Bangladesh

ABSTRACT Background Anaemia is commonly caused by iron deficiency and screened by haemoglobin (Hb) concentration in blood. There is a scarcity of longitudinal data on the relationship between maternal Hb levels during pregnancy and neurodevelopment in children. Objective To measure the relationship of maternal Hb concentrations during pregnancy on early child development. Methods This prospective cohort study included 1,720 mother-child dyads in rural Bangladesh. Maternal Hb concentrations were measured at 14 and 30 weeks of gestation. The child’s Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 18 months of age were measured using Bayley Scales of Infant and Toddler Development (BSID-II). Data on socio-demographic characteristics, anthropometrics, mothers’ IQ and children’s home stimulation were also collected. Bivariate and multivariable-adjusted linear regression analyses were used to explore associations of maternal Hb with child development. Results Mean Hb concentrations at 14 and 30 weeks of gestation were 116.6 g/L (±12.7) and 114.7 g/L (±12.7), respectively. Mean MDI and PDI scores among 18-month-old children were 78.9 (±12.4) and 93.8 (±13.7), respectively. Maternal 14-week Hb concentration was correlated with PDI (r = 0.06; p < 0.05) and 30-week Hb concentrations was correlated with MDI (r = 0.05; p < 0.05). Multivariable adjusted linear regression analysis showed that an increase in 14-week Hb concentrations increased the PDI scores among boys (β = 0.09; 95% CI: 0.02, 0.16). Hb concentrations at 30 weeks of gestation were not associated with MDI or PDI scores. Conclusion Higher maternal Hb concentrations at 14 weeks of gestation were associated with higher PDI among 18-month-old boys in Bangladesh.

Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695–0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722–0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657–0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712–0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.

Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age

BackgroundPrevious studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors.MethodsA co-twin control design was employed to test whether prenatal phthalate exposure was associated with children’s neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility.ResultsMaternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (β = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (β = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins.ConclusionsNeurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Outcomes at 18–24 Months of Infants with Birth Weight under 500 g Born in Korea during 2013–2017: A Nationwide Cohort Study

Introduction: This study aimed to investigate the outcomes of infants at 18–24 months born in the Korean Neonatal Network with a birth weight <500 g. Methods: The anthropometric and neurodevelopmental data of infants with a birth weight <500 g at a gestational age of ≥22 weeks who were registered in the Korean Neonatal Network 2013–2017 and followed up at a corrected age of 18–24 months were reviewed. Neurodevelopmental impairment was defined as the presence of any of the following: (1) cerebral palsy; (2) severe visual impairment; (3) hearing impairment; or (4) cognitive impairment. Cognitive impairment was defined as (1) a Bayley Scales of Infant Development-II Mental Development Index score <70; and (2) Bayley Scales of Infant and Toddler Development-III Cognitive and Language Composite scores <85. Cognitive testing was performed for infants with suspected problems upon clinician’s referral to developmental specialists. Results: At a median corrected age of 20 months, 26/52 (50%) of included infants had neurodevelopmental impairment. Cerebral palsy, severe visual impairment, wearing of glasses, hearing impairment, and cognitive impairment occurred in 22%, 0%, 8%, 5%, and 57% of the included infants, respectively. The proportions of infants with <2 standard deviations of weight, length, and head circumference were 54%, 52%, and 56%, respectively. The majority (70%) of infants were rehospitalized, and the most common cause was respiratory problems. Conclusion: Half of infants with a birth weight <500 g in Korea may exhibit neurodevelopmental impairment and growth retardation at a corrected age of 18–24 months. Multidisciplinary follow-up along with continuous rehabilitation will be needed to improve neurological and physical development in this special population.

Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study.

Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): , ] and 3.06 points (95% CI: , ) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: , ) in boys' MDI scores and 1.90 points (95% CI: , ) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: , ) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.

Genetic and clinical variables act synergistically to impact neurodevelopmental outcomes in children with single ventricle heart disease

BackgroundRecent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes remains less understood. Outcomes analyses using genetics are complicated by the intrinsic severity of the CHD lesion and interactions with conditionally dependent clinical variables.MethodsBayesian Networks were applied to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD.ResultsAs isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increase the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables act synergistically to further increase the probability of a low MDI score by 10-fold. The absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increase the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increase the probability of a good outcome by 59-fold.ConclusionsOur analyses suggest a modest genetic contribution to neurodevelopmental outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.

Hair and cord blood element levels and their relationship with air pollution, dietary intake, gestational diabetes mellitus, and infant neurodevelopment

Exposure to a range of elements, air pollution, and specific dietary components in pregnancy has variously been associated with gestational diabetes mellitus (GDM) risk or infant neurodevelopmental problems. We measured a range of pregnancy exposures in maternal hair and/or infant cord serum and tested their relationship to GDM and infant neurodevelopment. A total of 843 pregnant women (GDM=224, Non-GDM=619) were selected from the Complex Lipids in Mothers and Babies cohort study. Forty-eight elements in hair and cord serum were quantified using inductively coupled plasma-mass spectrometry analysis. Binary logistic regression was used to estimate the associations between hair element concentrations and GDM risk, while multiple linear regression was performed to analyze the relationship between hair/cord serum elements and air pollutants, diet exposures, and Bayley Scales of infant neurodevelopment at 12 months of age. After adjusting for maternal age, BMI, and primiparity, we observed that fourteen elements in maternal hair were associated with a significantly increased risk of GDM, particularly Ta (OR=9.49, 95% CI: 6.71, 13.42), Re (OR=5.21, 95% CI: 3.84, 7.07), and Se (OR=5.37, 95% CI: 3.48, 8.28). In the adjusted linear regression model, three elements (Rb, Er, and Tm) in maternal hair and infant cord serum were negatively associated with Mental Development Index scores. For dietary exposures, elements were positively associated with noodles (Nb), sweetened beverages (Rb), poultry (Cs), oils and condiments (Ca), and other seafood (Gd). In addition, air pollutants PM2.5 (LUR) and PM10 were negatively associated with Ta and Re in maternal hair. Our findings highlight the potential influence of maternal element exposure on GDM risk and infant neurodevelopment. We identified links between levels of these elements in both maternal hair and infant cord serum related to air pollutants and dietary factors.

Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.

Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants. To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. We included randomised controlled trials (RCTs) and quasi-RCTs comparing prebiotics with placebo or no prebiotics in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants. The primary outcomes were NEC and all-cause mortality, and the secondary outcomes were late-onset invasive infection, duration of hospitalisation since birth, and neurodevelopmental impairment. Two review authors separately evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference (MD), with associated 95% confidence intervals (CIs). The primary outcomes of interest were NEC and all-cause mortality; our secondary outcome measures were late-onset (> 48 hours after birth) invasive infection, duration of hospitalisation, and neurodevelopmental impairment. We used the GRADE approach to assess the level of certainty of the evidence. We included seven trials in which a total of 705 infants participated. All the trials were small (mean sample size 100). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were potential sources of bias in three of the trials. The studied prebiotics were fructo- and galacto-oligosaccharides, inulin, and lactulose, typically administered daily with enteral feeds during birth hospitalisation. Meta-analyses of data from seven trials (686 infants) suggest that prebiotics may result in little or no difference in NEC (RR 0.97, 95% CI 0.60 to 1.56; RD none fewer per 1000, 95% CI 50 fewer to 40 more; low-certainty evidence), all-cause mortality (RR 0.43, 95% CI 0.20 to 0.92; 40 per 1000 fewer, 95% CI 70 fewer to none fewer; low-certainty evidence), or late-onset invasive infection (RR 0.79, 95% CI 0.60 to 1.06; 50 per 1000 fewer, 95% CI 100 fewer to 10 more; low-certainty evidence) prior to hospital discharge. The certainty of this evidence is low because of concerns about the risk of bias in some trials and the imprecision of the effect size estimates. The data available from one trial provided only very low-certainty evidence about the effect of prebiotics on measures of neurodevelopmental impairment (Bayley Scales of Infant Development (BSID) Mental Development Index score < 85: RR 0.84, 95% CI 0.25 to 2.90; very low-certainty evidence; BSID Psychomotor Development Index score < 85: RR 0.24, 95% 0.03 to 2.00; very low-certainty evidence; cerebral palsy: RR 0.35, 95% CI 0.01 to 8.35; very low-certainty evidence). The available trial data provide low-certainty evidence about the effects of prebiotics on the risk of NEC, all-cause mortality before discharge, and invasive infection, and very low-certainty evidence about the effect on neurodevelopmental impairment for very preterm or VLBW infants. Our confidence in the effect estimates is limited; the true effects may be substantially different. Large, high-quality trials are needed to provide evidence of sufficient validity to inform policy and practice decisions.

Association of Moderate Hypothermia at Admission with Short-Term and Long-Term Outcomes in Extremely Low Birth Weight Infants

Purpose: Extremely low birth weight (ELBW) infants exhibit immature thermoregulation and are easily exposed to hypothermia. We investigated the association between hypothermia on admission with short- and long-term outcomes.Methods: Medical records of ELBW infants admitted to the neonatal intensive care unit of a tertiary medical center between June 2012 and February 2017 were retrospectively analyzed. Upon admission, the axillary body temperature was measured. Moderate hypothermia was defined as admission temperature below 36 ℃.Results: A total of 208 infants with gestational age of 26.4±2.3 weeks and birth weight of 746.7±154.9 g were included. Admission temperature ranged from 33.5 to 36.8 ℃ (median 36.1 ℃). Univariate analyses of maternal and infant characteristics were performed for moderately hypothermic and control (normothermic to mildly hypothermic) infants. Lower gestational age, lower birth weight, and vaginal delivery correlated with moderate hypothermia. Logistic regression analyses adjusted for confounders revealed that the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) was associated with moderate hypothermia in ELBW infants. Moreover, abnormal mental developmental index scores on the Bayley Scales of Infant Development II at a corrected age of 18 to 24 months were associated with moderate hypothermia, but not with the psychomotor developmental index, incidence of blindness, deafness, or cerebral palsy.Conclusion: Moderate hypothermia at admission is not only correlated with short-term neonatal morbidities such as hsPDA, but may also be associated with long-term neurodevelopmental impairment in ELBW infants. Future large-scale studies are required to clarify the long-term consequences of hypothermia upon admission.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas

BackgroundThere is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. ObjectiveTo estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. MethodsConcentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC − ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. ResultsThe geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 μg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: −4.22, 3.36) for the 2nd, 6.50 (95%CI: −11.73, −1.27) for the 3rd, 5.42 (95%CI: −10.74, −0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: −7.90, −0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [−1.94 (95%CI: −3.18, −0.71)] and tAs [−1.61 (95%CI: −3.02, −0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. ConclusionsOur study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Prenatal exposure to benzotriazoles and benzothiazoles and child neurodevelopment: A longitudinal study

Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging benzo-heterocyclic compounds that may induce neurotoxicity. However, the effect of prenatal exposure to BTs (BTRs and BTHs) on child neurodevelopment has not been elucidated. We aimed to explore the associations between maternal urinary concentrations of BTs in single or in mixture with child neurodevelopment at the age of two. This study recruited 513 mother-child pairs based on a birth cohort from 2014 to 2015 in Wuhan. Maternal urinary concentrations of eight BTs (four BTRs and four BTHs) in the first, second, and third trimesters were measured. The mental development index (MDI) and psychomotor development index (PDI) of children, as two indexes of neurodevelopment, were assessed at two years old by the Bayley Scales. In the analyses of single BTs, prenatal average tolyltriazole (TTR) exposure level was associated with decreased boys' MDI scores (β = −2.84, 95 % CI: −5.11, −0.57) and prenatal average 1-H-benzotriazole (1-H-BTR) exposure level was associated with decreased boys' PDI scores (β = −1.44, 95 % CI: −2.70, −0.17), respectively. Maternal urinary concentrations of benzothiazole (BTH) in the 1st trimester (β = −1.79, 95 % CI: −2.78, −0.80), 2nd trimester (β = −1.14, 95 % CI: −2.19, −0.09), and the prenatal average exposure (β = −2.15, 95 % CI: −3.69, −0.61) were also negatively associated with boys' PDI scores. However, no significantly negative association was observed among girls. In the further mixture analysis, the quantile g-computation model found a significant negative association between prenatal average concentrations of BTs in mixture and boys' PDI scores [β = −4.80 (95 % CI: −9.08, −0.52)], and BTH weighted the highest in the negative association. As far as we know, this is the first research to estimate the effect of prenatal exposure to BTs on child neurodevelopment. The findings showed that prenatal exposure to BTs was negatively associated with neurodevelopment among boys, suggesting that the associations may be modified by infant sex.

Exploring brainstem auditory evoked potentials and mental development index as early indicators of autism spectrum disorders in high-risk infants.

This study of infants from Hubei Province, China examined brainstem auditory evoked potentials (BAEP) and mental development index (MDI) as possible early indicators associated with autism spectrum disorders (ASD). The 34 ASD cases and 102 controls who had recovered from perinatal conditions were matched for age, sex, gestational age, birth weight and maternal age. BAEP absolute latencies (AL) I, III, V and interpeak latencies (IPL) I-III, III-V, I-V were compared in ASD cases and controls at ages 1, 3 and 6months. MDI scores were compared in these infants from 1month to 2 years old. Multiple logistic regression analysis was performed to test associations among ASD, BAEP and MDI. Results showed BAEP AL I, V and IPL III-V prolonged in the ASD group (p < 0.001), and MDI scores in ASD cases sharply declining from 12 to 24 months (p < 0.001). Regression analysis revealed odds ratios (OR) indicating that ASD was likely associated with abnormal values of BAEP AL I at 1 and 3months (ORAL I : 4.27; ORAL I : 4.13), and AL V at 6months (ORAL V : 7.85). Lower MDI scores (MDI < 80) in infants at 1, 3, and 6months were likely associated with ASD (ORMDI : 2.58; ORMDI : 3.83; ORMDI : 4.87). These data show that abnormal BAEP values and low MDI scores are independent factors associated with ASD, and that monitoring of BAEP and MDI during infancy might facilitate screening for ASD development.

Breast-Milk Rubidium and Other Trace Elements are Associated with Neurocognitive Development in Infants at Age of 8 Months

BackgroundTrace elements may affect neurodevelopment. There is a lack of data on breast-milk rubidium (Rb) in relation to neurodevelopment in infants. The associations of copper (Cu), zinc (Zn) and strontium (Sr) with neurodevelopment in infants remain uncertain. ObjectivesWe sought to evaluate the associations of breast-milk Rb (primary exposure), Cu, Zn, and Sr with neurodevelopment in infants at age 8 months. MethodsThe study cohort included 117 breastfed infants. Breast-milk samples were collected at 42 days and 8 months postpartum. Breast-milk Rb, Zn, Cu, and Sr were measured by inductively coupled plasma mass spectrometer. Neurodevelopment was assessed at age 8 months. The primary outcomes were attention and working memory scores, as evaluated by the A-not-B task. Other outcomes included the Mental Development Index (MDI) and Psychomotor Development Index (PDI) as evaluated by the Bayley Scale of Infant Development III. Generalized linear models and restricted cubic spline regression were used to assess the associations between trace elements and neurodevelopment indices. Bonferroni correction was conducted on all data presented. ResultsA nonlinear association was observed between breast-milk Rb at 42 days and infant’s attention at age 8 months (nonlinearity P = 0.037). Positive associations were observed with infant MDI scores and breast-milk Rb at 42 days (β = 4.46; P = 0.06) and 8 months (β = 3.79; P = 0.009) postpartum. Breast-milk Zn at 42 days was positively associated with infant’s attention (β = 0.31; P = 0.039). Sr at 42 days was positively correlated with attention (β = 0.18; P = 0.043) and MDI scores (β = 2.18; P = 0.015) at 8 months. Inverted U-shape associations were observed for breast-milk Cu at 42 days with infant attention and PDI scores. All associations were not significant after correction for multiple tests. ConclusionsOur data suggest that Rb, Zn, Cu, and Sr in breast milk at certain concentrations are associated with neurodevelopment in breastfed infants. Further studies are warranted to validate the findings.

An Investigation of the Relationship Between Dietary Patterns in Early Pregnancy and Maternal/Infant Health Outcomes in a Chinese Cohort.

BackgroundStudies assessing links between maternal diet and pregnancy outcomes have focused predominantly on individual nutrients or foods. However, nutrients are typically consumed in combinations of foods or beverages (i.e., dietary patterns). Taking into account the diet as a whole appreciates that nutrient absorption and metabolism are influenced by other nutrients and the food matrix.ObjectiveThe aim of this study was to investigate the relationship between dietary pattern consumption in early pregnancy and pregnancy/infant outcomes, including gestational diabetes mellitus, gestational weight gain, preeclampsia, placental weight, gestational age at delivery, small-for-gestational-age, large-for-gestational-age, macrosomia, measures of infant body composition, and scores on two main indices of the Bayley Scales of Infant Development [Mental Development Index (MDI) and the Psychomotor Development Index (PDI)] at 12 months.DesignOur study included 1,437 participants from a mother-infant cohort in Chongqing, China. Maternal diet was assessed using a 96-item food frequency questionnaire at 11–14 weeks gestation. Dietary patterns were constructed using principal component analysis. Multivariate regressions were performed to assess associations between maternal dietary pattern scores and pregnancy and infant outcomes, adjusting for confounders.ResultsTwo dietary patterns were derived: a pattern high in pasta, sweetened beverages, and oils and condiments (PSO-based dietary pattern) and a pattern high in fish, poultry, and vegetables (FPV-based dietary pattern). Higher scores on the PSO-based dietary pattern were associated with lower infant standardized scores on the PDI of the Bayley Scales of Infant Development, β (95% confidence interval) = −1.276 (−2.392, −0.160); lower placental weight, β (95% CI) = −6.413 (−12.352g, −0.473); and higher infant's tricep skinfold thickness at 6 weeks of age. β (95% CI) = 0.279 (0.033, 0.526). Higher scores on the FPV-based dietary pattern were associated with higher gestational weight gain between visit 1 (11–14 week's gestation) and 3 (32–34 week's gestation). β (95% CI) = 25.612 (13.255, 37.969). No significant associations were observed between dietary pattern scores and the remaining pregnancy/infant outcomes investigated or MDI scores on the Bayley Scales of Infant Development. This was the first study to investigate the association between dietary patterns in early pregnancy and infant neurocognition in a Chinese cohort.

Longitudinal Analysis of Amplitude-Integrated Electroencephalography for Outcome Prediction in Hypoxic-Ischemic Encephalopathy

To investigate the prognostic accuracy of longitudinal analysis of amplitude-integrated electroencephalography (aEEG) background activity to predict long-term neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. This single-center observational study included 149 neonates for derivation and 55 neonates for validation with moderate-severe HIE and of gestational age ≥35weeks at a tertiary neonatal intensive care unit. Single-channel aEEG background pattern, sleep-wake cycling, and seizure activity were monitored over 84hours during therapeutic hypothermia and rewarming, then scored for each 6-hour interval. Neurodevelopmental outcome was assessed using the Bayley Scales of Infant Development, Second Edition. Favorable outcome was defined as having both a Mental Development Index (MDI) score and Psychomotor Development Index (PDI) score ≥70, and adverse outcome was defined as either an MDI or a PDI <70 or death. Regression modeling for longitudinal analysis of repeatedly measured data was applied, and area under the receiver operating characteristic curve (AUC) was calculated. Longitudinal aEEG background analysis combined with sleep-wake cycling score had excellent predictive value (AUC, 0.90; 95% CI, 0.85-0.95), better than single aEEG scores at any individual time point. The model performed well in the independent validation cohort (AUC, 0.87; 95% CI, 0.62-1.00). The reclassification rate of this model compared with the conventional analysis of aEEG background at 48hours was 18% (24 patients); 14% (18 patients) were reclassified correctly. Our results were used to develop a user-friendly online outcome prediction tool. Longitudinal analysis of aEEG background activity and sleep-wake cycling is a valuable and accurate prognostic tool.

Neurodevelopmental outcomes at 6, 12, and 24 months of age in preterm infants with very low birth weights in Taiwan

To identify perinatal antecedents associated with neurodevelopmental impairment for very low birth weight (VLBW) preterm infants at ages 6, 12, and 24 months and the stability of neurodevelopmental assessments. A multicenter-based VLBW cohort was recruited, and the mental development index (MDI) and psychomotor development index (PDI) were used to evaluate children's neurodevelopment stages at ages 6, 12, and 24 months. Perinatal risk factors were determined through univariate and multivariate hierarchical linear analyses. Differences and predictability in MDI or PDI scores between ages 6 and 24 months were assessed. Covariates including father's education level; teenage pregnancy, multiple pregnancies; infant's gestational age, gender, and birth weight <999gm, duration of neonatal intensive care unit stay; and presence of various diseases were adversely associated with poor MDI or PDI scores in 8517 eligible VLBW infants during the study period. Polyhydramnios, emergency cesarean delivery, birth weight of <1250gm, and periventricular/intraventricular hemorrhage stage I-II were additional risk factors of VLBW infants with an adverse PDI score. An increased number of infants with a MDI or PDI score of <55at age 24 months was observed. Six-month MDI or PDI assessments had a low ability to predict outcomes at 24 months, with sensitivity and positive predictive values under 60% and specificity and negative predictive values over 85%. Multiple perinatal risk factors are associated with poor MDI and PDI scores among VLBW preterm infants. Six-month developmental assessments exhibited low sensitivity and positive predictive values for outcomes at 24 months.

Factors associated with neurodevelopmental impairment in preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication in preterm infants with very low birth weight and is known to lead to poor neurodevelopmental outcomes. This study aimed to identify factors associated with neurodevelopmental impairment (NDI) in patients with moderate to severe BPD. A total of 83 preterm infants born between 24- and 29-weeks' gestation who were admitted to the neonatal intensive care unit and developed moderate/severe BPD between 2013 and 2017 were retrospectively evaluated. Developmental assessment was performed at 18 to 24 months of corrected age using the Bayley Scales of Infant Development II (BSID-II). Patients with NDI (n=41) and without NDI (n=42) were compared. BSID-II Mental Development Index and Psychomotor Development Index scores were 87±11 and 83±8 in the non-NDI group and 57±12 and 52±8 in the NDI group, respectively (p<0.001). The NDI group had significantly lower birth weight (847±174 vs. 1012±192 g) and gestational age (26.1±1.3 and 27.6±1.6 weeks) compared to the non-NDI group (p<0.001). Intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, exposure to steroids, duration of respiratory support, and length of hospital stay were significantly higher in the NDI group (p<0.001). Many of the conditions in this study were found to be associated with poor neurodevelopmental outcomes in patients with BPD, such as prolonged respiratory support, prolonged hospitalization, intraventricular hemorrhage, retinopathy, and steroid therapy, can be avoided or prevented with strict protocols and prevention strategies. Appropriate management of comorbid risk factors may help prevent poor neurodevelopmental outcomes.

Prenatal and early postnatal exposure to ambient particulate matter and early childhood neurodevelopment: A birth cohort study

Adverse impacts of prenatal or postnatal ambient particulate matter exposure have been identified on offspring neurodevelopment. However, it is unclear whether the effect in the two exposure periods is different for early childhood neurodevelopment. This study aimed to evaluate and compare the associations of prenatal and early postnatal exposure to ambient particulate matter with offspring neurodevelopment at 2 years of age and to identify which period was more sensitive to the effects of ambient particulate matter on offspring neurodevelopment. A total of 1331 mother-child pairs from a birth cohort were included in this study from October 2013 to September 2014 in Wuhan, China. The concentrations of ambient daily fine particulate matter (PM2.5) and particulate matter less than 10μm in aerodynamic diameter (PM10) at each participant's home address during pregnancy and the first two years after birth were estimated by land-use regression models (LUR). Offspring neurodevelopment was measured by the Chinese revision of Bayley Scale of Infant Development (BSID-CR) for each child at 2 years of age. Mental developmental index (MDI) and psychomotor developmental index (PDI) from the BSID-CR were used as outcome variables. A generalized estimating equation (GEE) model was used to estimate the associations of prenatal and postnatal PM2.5 and PM10 exposure with offspring neurodevelopment. After adjusting for potential confounders, we found that both prenatal and early postnatal exposure to PM2.5 and PM10 were associated with decreased offspring MDI and PDI scores. Compared with prenatal exposure, the associations of early postnatal exposure to PM2.5 and PM10 with offspring MDI and PDI were stronger. This study indicates that exposure to ambient particulate matters, mainly during early postnatal period and to a lesser extent prenatally, is associated with impaired offspring neurodevelopment.

Associations of sleep duration with neurocognitive development in the first 2 years of life

The effect of sleep duration on neurocognitive development in infants and toddlers remains unclear. We aimed to investigate the relationship between sleep duration and neurocognitive development in infancy. Based on a prospective birth cohort, 2220 mother-infant pairs were enrolled in Wuhan, China, between January 2014 and October 2017. Sleep duration was evaluated at 1, 6, 12 and 24months via parent-report questionnaires. To assess the children's neurocognitive development at 2years old, the Bayley Scales of Infant Development of China Revision was used to assess the Mental Development Index (MDI) and Psychomotor Development Index (PDI). A group-based semiparametric mixture model was used to estimate the developmental trajectories of the total, nighttime and daytime sleep duration. The associations of sleep duration at each age and sleep duration trajectories with Mental Development Index scores and Psychomotor Development Index scores were analysed using generalized linear models. Daytime sleep duration (≥ 10.0hr) at 1 month was associated with lower Mental Development Index scores (β=-3.55, 95% confidence interval: -6.02, -1.08) and lower Psychomotor Development Index scores (β=-2.87, 95% confidence interval: -4.94, -0.81). Nighttime sleep duration (≤ 7.0hr) at 6months was associated with lower Mental Development Index scores (β=-7.02, 95% confidence interval: -11.02, -3.01). Daytime sleep duration (&gt; 4 hr) and nighttime sleep duration (&lt; 8hr) at 12months were associated with lower Mental Development Index scores (β=-9.17, 95% confidence interval: -15.35, -2.98) and lower Psychomotor Development Index scores (β=-8.14, 95% confidence interval: -13.56, -2.71), respectively. In further sleep duration trajectories analyses, lower Mental Development Index scores were significantly associated with the "decreased and then increased nighttime sleepers" trajectory (β=-4.39, 95% confidence interval: -8.02, -0.76), and "long and decreased daytime sleepers" trajectory (β=-2.44, 95% confidence interval: -4.58, -0.30). These results showed that short nighttime sleep duration and long daytime sleep duration in infancy were detrimental to children's neurocognitive development.