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1.
JAMA Netw Open ; 7(5): e2411905, 2024 May 01.
Article En | MEDLINE | ID: mdl-38758554

Importance: Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions. Objective: To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ. Design, Setting, and Participants: This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023. Exposures: Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report. Main Outcomes and Measures: Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level. Results: Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (ß = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (ß = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (ß = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months. Conclusions and Relevance: In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.


Cocaine , Intelligence , Prenatal Exposure Delayed Effects , Humans , Female , Pregnancy , Adult , Intelligence/drug effects , Infant , Cocaine/adverse effects , Prospective Studies , Male , Young Adult , Adolescent , Infant Behavior/drug effects , Longitudinal Studies , Infant, Newborn , Child Development/drug effects
2.
J Dev Orig Health Dis ; 15: e10, 2024 May 10.
Article En | MEDLINE | ID: mdl-38724487

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.


Bevacizumab , Child Development , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/physiopathology , Retinopathy of Prematurity/surgery , Male , Female , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Child, Preschool , Cross-Sectional Studies , Child , Child Development/drug effects , Child Development/physiology , Infant, Newborn , Infant, Premature , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Motor Skills/physiology , Intravitreal Injections
3.
JAMA Netw Open ; 7(5): e2411987, 2024 May 01.
Article En | MEDLINE | ID: mdl-38767917

Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.


Fluorides , Prenatal Exposure Delayed Effects , Humans , Female , Pregnancy , Child, Preschool , Fluorides/urine , Fluorides/adverse effects , Prospective Studies , Prenatal Exposure Delayed Effects/epidemiology , Adult , Male , Maternal Exposure/adverse effects , Maternal Exposure/statistics & numerical data , Child Development/drug effects , Child Behavior/drug effects , Pregnancy Trimester, Third/urine , Los Angeles/epidemiology
4.
Environ Int ; 187: 108726, 2024 May.
Article En | MEDLINE | ID: mdl-38733764

BACKGROUND: Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates during pregnancy may disrupt fetal developmental programming and influence early-life growth. We hypothesized that prenatal bisphenol and phthalate exposure was associated with alterations in adiposity through 4 years. This associations might change over time. METHODS: Among 1091 mother-child pairs in a New York City birth cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at three time points in pregnancy and child weight, height, and triceps and subscapular skinfold thickness at ages 1, 2, 3, and 4 years. We used linear mixed models to assess associations of prenatal individual and grouped bisphenols and phthalates with overall and time-point-specific adiposity outcomes from birth to 4 years. RESULTS: We observed associations of higher maternal urinary second trimester total bisphenol and bisphenol A concentrations in pregnancy and overall child weight between birth and 4 years only (Beta 0.10 (95 % confidence interval 0.04, 0.16) and 0.07 (0.02, 0.12) standard deviation score (SDS) change in weight per natural log increase in exposure), We reported an interaction of the exposures with time, and analysis showed associations of higher pregnancy-averaged mono-(2-carboxymethyl) phthalate with higher child weight at 3 years (0.14 (0.06, 0.22)), and of higher high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-carboxymethyl) phthalate, and mono-(2-ethylhexyl) phthalate with higher child weight at 4 years (0.16 (0.04, 0.28), 0.15 (0.03, 0.27), 0.19 (0.07, 0.31), 0.16 (0.07, 0.24), 0.11 (0.03, 0.19)). Higher pregnancy-averaged high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-2(ethyl-5-oxohexyl) phthalate concentrations were associated with higher child BMI at 4 years (0.20 (0.05, 0.35), 0.20 (0.05, 0.35), 0.22 (0.06, 0.37), 0.20 (0.05, 0.34), 0.20 (0.05, 0.34)). For skinfold thicknesses, we observed no associations. DISCUSSION: This study contributes to the evidence suggesting associations of prenatal exposure to bisphenols and high-molecular-weight phthalates on childhood weight and BMI.


Benzhydryl Compounds , Maternal Exposure , Phenols , Phthalic Acids , Prenatal Exposure Delayed Effects , Humans , Female , Phthalic Acids/urine , Phenols/urine , New York City , Pregnancy , Benzhydryl Compounds/urine , Child, Preschool , Maternal Exposure/statistics & numerical data , Cohort Studies , Infant , Adult , Environmental Pollutants/urine , Male , Infant, Newborn , Endocrine Disruptors/urine , Child Development/drug effects
5.
Sci Total Environ ; 927: 172366, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38614325

BACKGROUND: Concerns remain about the neurotoxic properties of the ubiquitous organophosphate esters (OPEs), the replacement of the toxicant polybrominated diphenyl ethers. OBJECTIVES: We examined the associations of prenatal exposure to OPEs and their mixtures with early-life neurodevelopment trajectories. METHODS: Totally 1276 mother-child pairs were recruited from the Shanghai Maternal-Child Pairs Cohort. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure the levels of 7 OPEs in cord serum. Ages and Stages Questionnaires was used to examine children's neuropsychological development at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Multiple linear regression and logistic regression model were performed to assess the relationships between OPEs exposure and neurodevelopment and trajectories. Mixtures for widely detected OPEs (n = 4) were investigated using quantile-based g-computation. RESULTS: Tributyl phosphate (TBP), tris (2-butoxy ethyl) phosphate (TBEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and 2-ethylhexyl diphenyl phosphate (EHDPP), had detection rates >50 %. TDCPP had the highest median concentration (1.02 µg/L) in cord serum. EHDPP concentrations were negatively associated with scores in most domains at 12 months of age, with effect values (ß) ranging from -1.89 to -0.57. EHDPP could negatively affect the total ASQ (OR = 1.07, 95 % CI: 1, 1.15) and gross-motor (OR = 1.09, 95 % CI: 1.02, 1.17) trajectory in infancy. Joint exposure to OPEs was associated with decreased scores in the total ASQ, gross-motor, fine-motor and problem-solving domain of 12-month-old infants, with ß ranging from -5.93 to -1.25. In addition, the qgcomp models indicated significant positive associations between the concentrations of OPEs mixtures and risks of the persistently low group of the total ASQ, gross-motor and fine-motor development in early childhood. The impact of OPEs was more pronounced in boys. DISCUSSION: Our findings suggested OPEs, especially EHDPP, had a persistently negative effect on neurodevelopment during the first 2 years.


Child Development , Esters , Organophosphates , Prenatal Exposure Delayed Effects , Humans , Female , China , Organophosphates/toxicity , Infant , Pregnancy , Child Development/drug effects , Maternal Exposure/statistics & numerical data , Male , Environmental Pollutants , Child, Preschool , Cohort Studies , Adult
6.
Article En | MEDLINE | ID: mdl-38673342

BACKGROUND: We assessed the relationship between the cognitive development of children and adolescents with phenylketonuria (PKU) and fluctuations in peripheral phenylalanine (Phe) levels. METHODS: We examined the neurocognitive performance of 33 children and adolescents with early treated PKU, of whom 18 were treated with sapropterin dihydrochloride, and 15 were on a classic diet. For 26 weeks, patients were assessed weekly for their blood phenylalanine (Phe) levels. Phe levels were analyzed for fluctuations indicated by the individual standard deviation. Fluctuations were compared to the standard deviation of 26 Phe level measurements before the study interval. We also assessed the concurrent IQ of the patients. This was repeated at one-, two-, and seven-year intervals. RESULTS: Full-scale IQ in patients treated with a classic diet did not change within the follow-up. In patients treated with Sapropterin dihydrochloride, however, there was a considerable gain in full-scale IQ. This was particularly true if blood Phe fluctuations increased in patients of this treatment group. CONCLUSIONS: Sapropterin dihydrochloride enhances Phe tolerance in patients with PKU. Increasing blood Phe fluctuations following enhanced Phe tolerance may indicate that the treatment not only allows patients to relax their Phe-restricted diet but also may support cognitive development in patients.


Biopterins , Biopterins/analogs & derivatives , Cognition , Phenylalanine , Phenylketonurias , Humans , Phenylketonurias/blood , Phenylketonurias/drug therapy , Phenylalanine/blood , Adolescent , Child , Cognition/drug effects , Male , Female , Biopterins/blood , Child, Preschool , Child Development/drug effects
7.
Alcohol Alcohol ; 59(3)2024 Mar 16.
Article En | MEDLINE | ID: mdl-38678371

AIMS: To examine the relationship between prenatal alcohol exposure (PAE) and children's behavioural and emotional development in a large generalizable sample of women and their children in Aotearoa New Zealand. METHODS: Using data from the Growing Up in New Zealand longitudinal cohort, we investigated the relationship between maternal PAE and behavioural and emotional development in 8-year-old children. We explored secondary outcomes including measures of language, executive function, academic achievement, and adaptive behaviour. RESULTS: We found no significant differences in the measures of behavioural and emotional development in children 8 years old based on alcohol consumption. No significant differences in behavioural and emotional development were found based on amount of PAE and when PAE occurred, despite controlling for a range of potential confounding factors, such as neighbourhood deprivation and maternal health measures. PAE was associated with significantly higher scores for parent-rated oral language indicating better oral language. In Maori mothers, PAE was significantly associated with an increased risk of higher scores on two of the Strengths and Difficulties Questionnaire subscales. CONCLUSIONS: We did not find an association between PAE and behavioural and emotional development in children aged 8 years. PAE and behavioural and emotional development are difficult to measure accurately, and the moderating variables between them are complex. Future analyses will require larger cohorts of mothers and their children using precise measures of PAE and outcomes to enable more precise estimates of association.


Alcohol Drinking , Child Behavior , Child Development , Emotions , Prenatal Exposure Delayed Effects , Humans , Female , New Zealand/epidemiology , Child , Prenatal Exposure Delayed Effects/psychology , Prenatal Exposure Delayed Effects/epidemiology , Pregnancy , Male , Longitudinal Studies , Emotions/drug effects , Child Development/drug effects , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Alcohol Drinking/psychology , Child Behavior/drug effects , Child Behavior/psychology , Adult , Cohort Studies , Executive Function/drug effects
8.
JAMA ; 331(19): 1629-1637, 2024 05 21.
Article En | MEDLINE | ID: mdl-38656759

Importance: The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. Objective: To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Design, Setting, and Participants: Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Exposure: Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. Main Outcome and Measures: The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Results: Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. Conclusion and Relevance: In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.


Betamethasone , Glucocorticoids , Humans , Betamethasone/administration & dosage , Betamethasone/adverse effects , Betamethasone/therapeutic use , Female , Follow-Up Studies , Pregnancy , Child , Male , Prospective Studies , Infant, Newborn , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Infant, Premature , Child Development/drug effects , Prenatal Care , Neurodevelopmental Disorders/prevention & control , Neurodevelopmental Disorders/epidemiology , Premature Birth/prevention & control
9.
Drug Alcohol Depend ; 259: 111284, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38640866

INTRODUCTION: Prenatal exposure to substance use is associated with long-term deficits in the neurodevelopment of children. The objective was to investigate the association between cognitive, motor, and language neurodevelopment at three years of age in infants prenatally exposed to substance use. MATERIAL AND METHODS: A prospective matched case-control study was conducted. Biomarkers of fetal exposure were measured in meconium samples. The Bayley Scales of Infant and Toddler Development (BSID-III) were used to calculate neurodevelopment scores. RESULTS: 32 non-exposed and 32 exposed infants were evaluated, of which 16 were exposed to cannabis, 8 to ethanol, 2 to cocaine and 6 to more than one substance. Normal BSID-III scores ≥85 in all domains, were detected in 23 exposed infants to any substance and 29 infants non-exposed. Neurodevelopmental delay was detected in the language domain, specifically in male infants exposed to cannabis. Two infants exposed to cannabis had a severe developmental delay (score<70). Infants exposed to any substance obtained significantly lower total scores than control infants in all domains. Infants exposed to cannabis obtained significantly lower composite scores in the cognitive and motor domains. Infants exposed to more than one substance had lower scores in motor skills. By gender, only males exposed obtained significantly lower composite scores than non-exposed males in the cognitive domain. CONCLUSIONS: The most common and severe neurodevelopmental delay at 36 months was detected in the domain of language in male infants prenatally exposed to cannabis. Neurodevelopmental disorders detected can enable an early intervention and plan therapeutic strategies.


Prenatal Exposure Delayed Effects , Substance-Related Disorders , Humans , Female , Male , Pregnancy , Case-Control Studies , Prospective Studies , Child, Preschool , Substance-Related Disorders/complications , Child Development/drug effects , Child Development/physiology , Infant , Adult , Developmental Disabilities/chemically induced , Neurodevelopmental Disorders/chemically induced , Motor Skills/drug effects , Motor Skills/physiology
10.
Dev Psychobiol ; 66(2)2024 Feb.
Article En | MEDLINE | ID: mdl-38646069

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses. Paired stimuli, S1, S2, were presented 500 msec apart. Higher P50 amplitude in response to S1 (P50S1microV) assesses excitation, and lower P50S2microV assesses inhibition in this paired-stimulus paradigm. Development of inhibition was related solely to maternal choline plasma concentration and folate supplementation at 16 weeks' gestation. Development of excitation was related only to maternal choline at 28 weeks. Higher maternal choline concentrations later in gestation did not compensate for earlier lower concentrations. At 4 years of age, increased behavior problems on the Child Behavior Checklist 1½-5yrs were related to both newborn inhibition and excitation. Incomplete development of inhibition and excitation associated with lower choline and folate during relatively brief periods of gestation thus has enduring effects on child development.


Choline , Evoked Potentials, Auditory , Folic Acid , Humans , Choline/pharmacology , Choline/metabolism , Female , Folic Acid/pharmacology , Male , Infant, Newborn , Pregnancy , Evoked Potentials, Auditory/physiology , Evoked Potentials, Auditory/drug effects , Child, Preschool , Fetal Development/physiology , Fetal Development/drug effects , Synaptic Transmission/physiology , Synaptic Transmission/drug effects , Adult , Gestational Age , Child Development/physiology , Child Development/drug effects
11.
J Pediatr ; 269: 113977, 2024 Jun.
Article En | MEDLINE | ID: mdl-38401788

OBJECTIVE: To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood. STUDY DESIGN: A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24 months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2 years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1]). RESULTS: After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6 months and continued through 12-24 months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12 months, and a lower mean IGF-1 levels at birth and 6 months. CONCLUSION: This study demonstrates a delayed impact of PAE on growth that manifested around 6 months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay.


Insulin-Like Growth Factor I , Nutritional Status , Prenatal Exposure Delayed Effects , Humans , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/analysis , Female , Philippines/epidemiology , Pregnancy , Infant , Male , Infant, Newborn , Longitudinal Studies , Child, Preschool , Alcohol Drinking/adverse effects , Child Development/drug effects , Adult , Fetal Blood/metabolism , Fetal Blood/chemistry , Glycerophospholipids/blood , Insulin-Like Peptides
12.
Curr Environ Health Rep ; 11(2): 300-316, 2024 Jun.
Article En | MEDLINE | ID: mdl-38369581

PURPOSE OF REVIEW: This scoping review aims to assess the impact of air pollution, traffic noise, heat, and green and blue space exposures on the physical and cognitive development of school-age children and adolescents. While existing evidence indicates adverse effects of transport-related exposures on their health, a comprehensive scoping review is necessary to consolidate findings on various urban environmental exposures' effects on children's development. RECENT FINDINGS: There is consistent evidence on how air pollution negatively affects children's cognitive and respiratory health and learning performance, increasing their susceptibility to diseases in their adult life. Scientific evidence on heat and traffic noise, while less researched, indicates that they negatively affect children's health. On the contrary, green space exposure seems to benefit or mitigate these adverse effects, suggesting a potential strategy to promote children's cognitive and physical development in urban settings. This review underscores the substantial impact of urban exposures on the physical and mental development of children and adolescents. It highlights adverse health effects that can extend into adulthood, affecting academic opportunities and well-being beyond health. While acknowledging the necessity for more research on the mechanisms of air pollution effects and associations with heat and noise exposure, the review advocates prioritizing policy changes and urban planning interventions. This includes minimizing air pollution and traffic noise while enhancing urban vegetation, particularly in school environments, to ensure the healthy development of children and promote lifelong health.


Air Pollution , Environmental Exposure , Humans , Child , Air Pollution/adverse effects , Adolescent , Environmental Exposure/adverse effects , Learning , Child Health , Child Development/drug effects , Air Pollutants/analysis , Air Pollutants/adverse effects , Noise, Transportation/adverse effects
13.
Eur J Pediatr ; 183(5): 2231-2238, 2024 May.
Article En | MEDLINE | ID: mdl-38393371

This study aims to assess the impact of non-fluorinated glucocorticoid use and varying doses on the long-term physical, neurological, and social-emotional development outcomes of offspring born to patients with systemic lupus erythematosus (SLE). The goal is to provide guidance on the appropriate dosage of glucocorticoids during pregnancy in SLE patients. We conducted a follow-up study on the offspring of SLE patients who had pregnancies and were admitted to our obstetrics department between January 1, 2016, and September 30, 2021. Patients who received immunosuppressants and dexamethasone were excluded from the study. The SLE patients were categorized into three groups based on their glucocorticoid use during pregnancy: hormone-free group, ≤ 10 mg/day group, and > 10 mg/day group (equivalent to prednisone). Most patients in the three groups were used hydroxychloroquine during pregnancy. We assessed the physical development status, including weight, height (length), and other relevant factors in three groups. Additionally, we utilized the Age and Stages Questionnaires, Third Edition (ASQ-3) to evaluate the development of communication, gross motor, fine motor, problem-solving, and personal-social. The social-emotional development status was assessed using the Age and Stages Questionnaires: Social-Emotional (ASQ: SE). We standardized the weight, height (length), body mass index, and ASQ-3 domain scores of children of different ages and genders into Z-scores for comparison. The results of this study demonstrated no statistically significant differences in the long-term physical development, neurological development, and social-emotional development outcomes of the offspring of SLE patients in three groups. However, while not reaching statistical significance, it was found that the offspring of the > 10 mg/day group had lower height (length) Z-scores and communication Z-scores compared to the other groups.   Conclusion: The use of non-fluorinated glucocorticoids during pregnancy and varying doses did not have a significant impact on the long-term physical, neurological, and social-emotional development outcomes of offspring born to SLE patients. However, the offspring of SLE patients treated with glucocorticoids > 10 mg/day during pregnancy may be necessary to strengthen the monitoring of height (length) and communication skills in the long term. What is Known: • Fetal exposure to glucocorticoids can have implications for the development of multiple systems and may persist after birth, potentially increasing the risk of neurological abnormalities and other diseases. • There is limited research on the long-term development of offspring born to SLE patients, especially the patients treated with glucocorticoids. What is New: • The use of non-fluorinated glucocorticoids during pregnancy and varying doses did not have a significant impact on the long-term outcomes of offspring born to SLE patients. • The offspring of SLE patients treated with glucocorticoids >10 mg/day during pregnancy may be necessary to strengthen the monitoring of height (length) and communication skills in the long term.


Child Development , Glucocorticoids , Lupus Erythematosus, Systemic , Pregnancy Complications , Prenatal Exposure Delayed Effects , Humans , Lupus Erythematosus, Systemic/drug therapy , Female , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Male , Follow-Up Studies , Child , Child Development/drug effects , Pregnancy Complications/drug therapy , Child, Preschool , Dose-Response Relationship, Drug , Adult , Infant , Infant, Newborn
14.
Environ Res ; 249: 118222, 2024 May 15.
Article En | MEDLINE | ID: mdl-38272290

BACKGROUND: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. OBJECTIVE: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. METHODS: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). RESULTS: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (ßper ten-fold increase = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (ßper ten-fold increase = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (ßper ten-fold increase = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (ßper ten-fold increase = -3.8, 95 % CI = -7.7, 0.1) but not girls (ßper ten-fold increase = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DISCUSSION: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.


Child Development , Pesticides , Prenatal Exposure Delayed Effects , Humans , Female , Pregnancy , Infant , Pesticides/urine , Pesticides/toxicity , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Male , Child Development/drug effects , Costa Rica , Maternal Exposure/adverse effects , Birth Cohort , Environmental Pollutants/urine , Adult , Cohort Studies , Young Adult
17.
Dev Med Child Neurol ; 65(6): 783-791, 2023 06.
Article En | MEDLINE | ID: mdl-36349526

AIM: To evaluate the association between ambient particulate matter no larger than 2.5 µm in diameter (PM2.5 ) during the prenatal and postnatal periods and infant neurodevelopmental parameters. METHOD: We conducted a population-based birth cohort study using the Taiwan Birth Cohort Study. Participants were assessed for developmental conditions through home interviews at 6 months and 18 months of age. Exposure to PM2.5 of mothers and infants during perinatal periods was estimated using hybrid kriging/land-use regression. The exposure was linked to each participant by home address. Logistic regression was then conducted to determine the risk of neurodevelopmental delay in relation to PM2.5 . RESULTS: A total of 17 683 term singletons without congenital malformations were included in the final analysis. PM2.5 during the second trimester was associated with increased risks of delays in gross motor neurodevelopmental milestones (adjusted odds ratio [aOR] 1.09 per 10 µg/m3 increase in exposure to PM2.5 ). Delayed fine motor development was also found to be related to exposure to PM2.5 in the second and third trimesters (aOR 1.06), as was personal-social skill (aOR 1.11 for the second trimester and 1.06 for the third). These neurodevelopmental parameters were unrelated to postnatal PM2.5 exposure. INTERPRETATION: Exposure to ambient PM2.5 during pregnancy was significantly related to delay in gross motor, fine motor, and personal-social development in this population-based study. WHAT THIS PAPER ADDS: Prenatal exposure to higher PM2.5 was associated with increased risk of delayed early neurodevelopment. The critical period for delayed gross motor development was the second trimester. The critical period for fine motor and personal-social development was the second and third trimesters.


Air Pollutants , Air Pollution , Child Development , Developmental Disabilities , Maternal Exposure , Prenatal Exposure Delayed Effects , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Air Pollutants/adverse effects , Air Pollution/adverse effects , Child Development/drug effects , Developmental Disabilities/epidemiology , Gestational Age , Logistic Models , Longitudinal Studies , Maternal Exposure/adverse effects , Particulate Matter/adverse effects , Prenatal Exposure Delayed Effects/epidemiology , Taiwan/epidemiology , Adult
18.
Toxins (Basel) ; 14(12)2022 12 03.
Article En | MEDLINE | ID: mdl-36548752

Aflatoxin can cross the blood-brain barrier, damage brain tissues, and have the potential to harm the development of the human brain. Although dietary aflatoxin exposure is common in children, there is a paucity of data on aflatoxin exposure and child developmental outcomes. The child's cognitive, motor, and language functions were assessed using the Bayley Scales of Infant and Toddler Development-III or BSID-III at the same time points. Association between exposure to aflatoxin and subtests of BSID-III were examined using mixed-effect linear regression. Aflatoxin assays were performed on 194, 167, and 163 children at 15, 24, and 36 months of age, and chronic aflatoxin exposure was detected in 20.6%, 16.8%, and 60.7% of children, respectively. Multi-variable analyses showed that aflatoxin exposure was independently related to the children's cognitive score (ß: -0.69; 95% CI: -1.36, -0.02), receptive language score (ß: -0.90; 95% CI: -1.62, -0.17), and expressive language score (ß: -1.01; 95% CI: -1.96, -0.05). We did not observe any association between exposure to aflatoxin and the motor function of children. Chronic exposure to aflatoxin exposure was linked to reduced cognitive, expressive, and receptive language scores of the study children. Further research is needed in a different setting to confirm this novel finding.


Child Development , Cognition , Language Development , Child, Preschool , Humans , Infant , Bangladesh/epidemiology , Child Development/drug effects , Cognition/drug effects , Longitudinal Studies , Aflatoxins/toxicity , Dietary Exposure/adverse effects
19.
Pak J Pharm Sci ; 35(1(Special)): 361-364, 2022 Jan.
Article En | MEDLINE | ID: mdl-35236648

To explore the application effect of aminophylline combined with caffeine citrate and GMs in the evaluation of neurodevelopmental treatment and follow-up in high-risk preterm infants. A retrospective analysis of 66 high-risk preterm infants admitted to Hengshui People's Hospital from January 2020 to June 2021 was conducted. The children who received only conventional treatment were set as the control group, while those who received aminophylline and caffeine citrate on the basis of conventional treatment were set as the experimental group, 33 cases each group; GMs were used to evaluate the neurodevelopmental function of the children, and the treatment effect was analyzed. The normal proportion of GMs assessment results in the twisting phase and restless movement phase of the experimental group was superior to the control group (P<0.05); The proportion of children with normal neurodevelopment in the experimental group was significantly higher than that in the control group (P<0.05). Aminophylline in combination with caffeine citrate can help promote the neurodevelopment of children and improve their physical health using GMs assessment in the treatment and follow-up of high-risk preterm infants.


Aminophylline/therapeutic use , Caffeine/therapeutic use , Central Nervous System/drug effects , Central Nervous System/growth & development , Child Development/drug effects , Citrates/therapeutic use , Aminophylline/administration & dosage , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/therapeutic use , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/therapeutic use , Humans , Infant , Infant, Premature , Motor Activity
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