Abnormal neurological soft signs in babies born to smoking mothers were associated with lower breastfeeding for first three months.

AIM: We examined associations between neurological alterations in infants born to smoking mothers and breastfeeding success at discharge and three months of age. METHODS: This 2016 study compared 35 normal weight infants born to smoking mothers at 37-41 weeks and 35 matched controls born to non-smoking mothers at the Maternity Hospital of Careggi University, Florence, Italy. Neonatal behaviour was evaluated using the neurological soft signs (NSS) component of the Graham-Rosenblith Scale. Breastfeeding variables were measured using the LATCH score that covers: breast latching, audible swallowing, type of nipple, mother's comfort and help they needed to hold their baby to their breast. A questionnaire on excessive crying and feeding was distributed at discharge, and further data were collected during a three-month telephone interview. RESULTS: At discharge, the infants born to smoking mothers had a significantly lower LATCH score and significantly poorer performance on several items of the NSS component than the controls. The LATCH score and number of NSS were inversely proportional. At the three-month follow-up only 57.1% of the smoking group infants were breastfeeding compared with 87.5% of the control infants (p < 0.01). CONCLUSION: Infants with smoking mothers displayed altered neurobehavioural profiles and had a difficult start to breastfeeding.

[The Cognitive, Language and Motor Development of Prenatal Methamphetamine- and Opioid-exposed Children]. / Die kognitive, sprachliche und motorische Entwicklung pränatal methamphetamin- und opioid-exponierter Kinder.

OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.

Clinical signs and electroencephalographic patterns of emergence from sevoflurane anaesthesia in children: An observational study.

BACKGROUND: Few studies have systematically described relationships between clinical-behavioural signs, electroencephalographic (EEG) patterns and age during emergence from anaesthesia in young children. OBJECTIVE: To identify the relationships between end-tidal sevoflurane (ETsevoflurane) concentration, age and frontal EEG spectral properties in predicting recovery of clinical-behavioural signs during emergence from sevoflurane in children 0 to 3 years of age, with and without exposure to nitrous oxide. The hypothesis was that clinical signs occur sequentially during emergence, and that for infants aged more than 3 months, changes in alpha EEG power are correlated with clinical-behavioural signs. DESIGN: An observational study. SETTING: A tertiary paediatric teaching hospital from December 2012 to August 2016. PATIENTS: Ninety-five children aged 0 to 3 years who required surgery below the neck. OUTCOME MEASURES: Time-course of, and ETsevoflurane concentrations at first gross body movement, first cough, first grimace, dysconjugate eye gaze, frontal (F7/F8) alpha EEG power (8 to 12 Hz), frontal beta EEG power (13 to 30 Hz), surgery-end. RESULTS: Clinical signs of emergence followed an orderly sequence of events across all ages. Clinical signs occurred over a narrow ETsevoflurane, independent of age [movement: 0.4% (95% confidence interval (CI), 0.3 to 0.4), cough 0.3% (95% CI, 0.3 to 0.4), grimace 0.2% (95% CI, 0 to 0.3); P > 0.5 for age vs. ETsevoflurane]. Dysconjugate eye gaze was observed between ETsevoflurane 1 to 0%. In children more than 3 months old, frontal alpha EEG oscillations were present at ETsevoflurane 2.0% and disappeared at 0.5%. Movement occurred within 5 min of alpha oscillation disappearance in 99% of patients. Nitrous oxide had no effect on the time course or ETsevoflurane at which children showed body movement, grimace or cough. CONCLUSION: Several clinical signs occur sequentially during emergence, and are independent of exposure to nitrous oxide. Eye position is poorly correlated with other clinical signs or ETsevoflurane. EEG spectral characteristics may aid prediction of clinical-behavioural signs in children more than 3 months.

Effect of Anesthesia on the Developing Brain: Infant and Fetus.

The potential for commonly used anesthetics and sedatives to cause neuroapoptosis and other neurodegenerative changes in the developing mammalian brain has become evident in animal studies over the past 15 years. This concern has led to a number of retrospective studies in human infants and young children, and some of these studies observed an association between exposure to general anesthesia as an infant, and later neurobehavioral problems in childhood. This association is particularly evident for prolonged or repeated exposures. Because of the significant growth of fetal interventions requiring sedation and analgesia for the fetus, or because of maternal anesthetic effects, this concern about anesthetic neurotoxicity is relevant for the fetus. The potential for anesthetic neurotoxicity is the most important clinical and research problem in the field of pediatric anesthesiology. This review will first briefly summarize the rapid brain growth and development in the fetus and neonate. Next, animal model data of anesthetic neurotoxicity in the fetus and neonate will be presented, followed by a review of recent human clinical anesthetic neurotoxicity trials. Finally, the rationale for studying dexmedetomidine as a potential neuroprotectant agent in anesthetic neurotoxicity will be reviewed along with study design for two human clinical trials involving dexmedetomidine.

Higher alcohol consumption in early pregnancy or low-to-moderate drinking during pregnancy may affect children's behaviour and development at one year and six months.

AIM: It is unclear whether low-to-moderate alcohol consumption during pregnancy affects child development. This study examined the effects that a mother's self-reported alcohol consumption had on her pregnancy and her child's birth, behaviour and development. METHODS: We asked 291 Swedish women to report their alcohol consumption before and during pregnancy using the Alcohol Use Disorders Identification Test (AUDIT); provide data on their pregnancy, labour and neonatal period; and complete a child behaviour and development questionnaire when their child was one year and six months of age. The mothers were separated into four subgroups based on their AUDIT scores. RESULTS: There were no group differences in gestational length, but children were shorter at birth if their mother drank during pregnancy. Mothers with the highest alcohol consumption before pregnancy were generally younger and more likely to smoke, have unplanned pregnancies and have children who displayed behavioural problems than controls who reported abstinence before and during pregnancy. Mothers who drank more during pregnancy than before were more likely to have had abortions and unplanned pregnancies and less likely to breastfeed for more than six months. CONCLUSION: Our results suggested that low-to-moderate alcohol consumption during pregnancy may negatively influence a child's development and behaviour in several ways.

Neonatal abstinence syndrome: Neurobehavior at 6 weeks of age in infants with or without pharmacological treatment for withdrawal.

Use and abuse of prescription opioids and concomitant increase in Neonatal Abstinence Syndrome (NAS), a condition that may lead to protracted pharmacological treatment in more than 60% of infants, has tripled since 2000. This study assessed neurobehavioral development using the NICU Network Neurobehavioral Scale in 6-week old infants with prenatal methadone exposure who did (NAS+; n = 23) or did not (NAS-; n = 16) require pharmacological treatment for NAS severity determined by Finnegan Scale. An unexposed, demographically similar group of infants matched for age served as comparison (COMP; n = 21). NAS+, but not NAS- group, had significantly lower scores on the regulation (p < .01) and quality of movement (p < .01) summary scales than the COMP group. The NAS+ and NAS- groups had higher scores on the stress-abstinence scale than the COMP group (p < .05). NAS diagnosis (NAS +) was associated with poorer regulation and quality of movement at 6 weeks of age compared to infants without prenatal methadone exposure from the same demographic.

Epigenetic Regulation of Placental NR3C1: Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking?

Epigenetic regulation of the placental glucocorticoid receptor gene (NR3C1) was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP-exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale was administered 7 times over the 1st postnatal month; methylation of placental NR3C1 was assessed via bisulfite pyrosequencing. Increased placental NR3C1 methylation was associated with increased infant attention and self-regulation, and decreased lethargy and need for examiner soothing over the 1st postnatal month. A causal steps approach revealed that NR3C1 methylation and MSDP were independently associated with lethargic behavior. Although preliminary, results highlight the importance of epigenetic mechanisms in elucidating pathways to neurobehavioral alterations from MSDP.

Sculpting infant soothability: the role of prenatal SSRI antidepressant exposure and neonatal SLC6A4 methylation status.

The role of prenatal Selective Serotonin Reuptake Inhibitor (SSRI) exposure and SLC6A4 promoter methylation status in shaping soothability at 3 and 6 months of age, for infants exposed to antidepressant medication prenatally (n = 46) and those not exposed (n = 69) was investigated. SSRI exposure status and duration of exposure (number of days) were examined along with neonatal methylation status at mean CpG 9,10 and via factor analysis across 10 CpG sites yielding PC1 (CpGs sites: 3,4,5,7) and PC2 (CpG 1,8). Analyses revealed interactions for methylation markers and SSRI exposure variables. A significant interaction between SSRI exposure and mean SLC6A4 methylation at CpG 9,10 and separately for PC1 emerged, controlling for multiple birth/medical and background covariates (e.g., Apgar scores, maternal education). Increased neonatal methylation status was associated with increased soothability changes from 3 to 6 months among infants prenatally exposed to SSRIs.

[Prenatal lead exposure related to cord blood brain derived neurotrophic factor (BDNF) levels and impaired neonatal neurobehavioral development].

OBJECTIVE: To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. METHODS: All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 µmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 µmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. RESULTS: Lead content in high exposure group was (0.613±0.139) µmol/L, and higher than (0.336±0.142) µmol/L in low exposure group (t=3.21, P<0.001) . NBNA summary score (36.35±1.86), active muscle tension score (6.90±0.27) and general assessment score (5.93±0.32) in high exposure group were lower than those (38.13±0.96, 7.79±0.35, 6.00±0.00) in low exposure group (t values were 8.21, 10.23, 2.32, respectively, P values were <0.001, <0.001 and 0.037) . BDNF content in high exposure group which was (3.538±1.203) ng/ml was higher than low exposure group (2.464±0.918) ng/ml (t=7.60, P<0.001). The correlation analysis found that the cord blood BDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were <0.001, respectively) . CONCLUSION: Prenatal lead exposure results poor neonatal neurobehavioral development and cord blood BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.

Lactose-Free Milk or Soy-Based Formulas Do Not Improve Caregivers' Distress or Perceptions of Difficult Infant Behavior.

OBJECTIVES: The aim of the study was to test the hypothesis that caregiver-reported difficulties in infant behavior and caregivers' distress will significantly improve on lactose-free (LF) milk-based or LF soy-based formulas compared with a milk-based, lactose-containing formula. METHODS: In this double-blind randomized controlled trial, infants (mean age: 4.97 weeks) with caregiver-reported feeding problems on a milk-based lactose-containing formula were randomized to receive either LF milk-based (n = 96), LF soy-based (n = 97), or milk-based, lactose-containing (n = 103) formula. Study formula was infants' sole item of diet for 14 days. Infants' caregivers completed measures of infant behavior and caregivers' distress for the week preceding baseline and again for the week preceding the 14-day follow-up. RESULTS: Infants who received LF milk or LF soy-based formulas did not significantly differ from those who received milk-based, lactose-containing formula on follow-up caregiver-reported measures of infant difficultness from the Infant Characteristics Questionnaire, F(2, 277) = 0.83, nor on measures of caregivers' distress, assessed with measures of caregivers' mental health and parenting efficacy, F(2, 285) = 0.73-1.07. Across the 3 formula groups, scores on outcome measures significantly improved from baseline to follow-up (P < 0.001). CONCLUSIONS: Our study does not support LF milk or LF soy-based formulas to alleviate common infant behaviors such as fussiness, crying, or need for attention. Moreover, the data suggest that some difficulties in infant behaviors, as well as caregivers' distress and perceived efficacy in parenting difficult infants, may improve within a couple weeks of reporting difficulties to the pediatrician.

Infant emotional withdrawal: a precursor of affective and cognitive disturbance in fetal alcohol spectrum disorders.

BACKGROUND: Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. METHODS: The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years. RESULTS: Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. CONCLUSIONS: This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother-infant interaction, infant temperament, or other socioemotional aspects of the infant's environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS.

Prenatal exposure to manganese at environment relevant level and neonatal neurobehavioral development.

BACKGROUND: Effects of prenatal Manganese (Mn) exposure at an environmental relevant level on neonatal neurodevelopment remains unclear. OBJECTIVES: In the multi-center study, we assessed the impact of low level prenatal Mn exposure on neonatal behavioral neurological assessments (NBNA), and explore a threshold umbilical cord blood Mn on neonatal neurological development. METHODS: We investigated 933 mother-newborn pairs in Shanghai, China, from 2008 through 2009. Umbilical cord serum concentrations of Mn were measured and NBNA tests were conducted. The NBNA contains five clusters: behavior, active tone, passive tone, primary reflexes and general assessment with a maximal total score of 40. The score<37 is defined as low. RESULTS: The median serum Mn concentration was 4.0 µg/L. Of the 933 infants, 44 (4.7%) had low NBNA. After adjusting for potential confounders, a high level of Mn (≥ 75th percentile ) was associated with a lower NBNA score (adjusted ß=-1.1, 95% CI: -1.4-0.7, p<0.01) and a higher risk of low NBNA (adjusted OR=9.4, 95% CI: 3.4-25.7, p<0.01). A nonlinear relationship was observed between cord serum Mn and NBNA after adjusting for potential confounders. NBNA score decreased with increasing Mn levels after 5.0 µg/L(LgMn ≥ 0.7). The cord serum Mn ≥ 5.0 µg/L had adverse effects on behavior, active tone and general reactions of clusters (p<0.001). CONCLUSIONS: High prenatal Mn exposure even at an environmental relevant level, is associated with poor fetal neurobehavioral development in a nonlinear pattern. A threshold cord serum Mn of 5.0 µg/L existed for lower neonatal behavioral neurological assessments.

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis.

BACKGROUND: It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use. METHODS: Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012. RESULTS: There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33-143 and 45-85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen's benchmark criteria. CONCLUSIONS: Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of 'core' phenotypes.

Infant Behaviors, Prenatal Cocaine Exposure, and Adult Intelligence.

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.

Neurobehavioral outcomes of infants exposed to buprenorphine-naloxone compared with naltrexone during pregnancy.

BACKGROUND: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. AIMS: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. STUDY DESIGN: Multi-centered prospective cohort study. SUBJECTS: Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. OUTCOME MEASURES: Infants were evaluated at 4-6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4-6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. CONCLUSIONS: In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4-6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy.

Association of cord blood levels of lead, arsenic, and zinc with neurodevelopmental indicators in newborns: a birth cohort study in Chitwan Valley, Nepal.

In this study, we aimed to investigate the association between in utero toxic (lead [Pb] and arsenic [As]) and essential element (zinc [Zn]) levels and neurodevelopmental indicators after birth in Chitwan Valley, Nepal. We conducted a hospital-based birth cohort study with 100 pregnant women in Chitwan, Nepal. We measured Pb, As, and Zn concentrations in cord blood. We assessed 100 infants at 1 day after birth, using the Brazelton neonatal behavioral assessment scale, third edition (NBAS III). Multivariate regression was performed to adjust for mother's age, parity, educational level, and body mass index (BMI); family income; and newborn's birth weight, gestational age, and age in hours at the time of NBAS III assessment. Among the 7 clusters of NBAS III, the motor cluster score was inversely associated with the cord blood levels of Pb (coefficient=-2.15, at 95% confidence interval [CI]=-4.27 to -0.03). The cord blood levels of As were inversely associated with the state regulation cluster score (coefficient=-6.71, at 95% CI=-12.17 to -1.24). The cord blood levels of Zn were not associated with NBAS III scores. The cord blood levels of Pb and As, but not Zn, showed significant inverse association with the neurodevelopment of newborns. These results suggest that high levels of Pb or As exposure during the prenatal period may induce retardation during in utero neurodevelopment.

Impact of low-level gestational exposure to organophosphate pesticides on neurobehavior in early infancy: a prospective study.

BACKGROUND: National data suggest widespread gestational exposure to organophosphate pesticides (OPs) based on the detection of OP metabolites in the urine of pregnant women. Associations with early infant neurobehavior are largely understudied, with only two studies reporting abnormal reflexes in newborns in association with gestational exposure to OPs. Our objective was to utilize biological markers of OP metabolites in pregnant women and a comprehensive assessment of infant neurobehavior to determine the association of gestational exposure to OPs with neurobehavioral outcomes during early infancy. METHODS: Among a cohort of 350 mother/infant pairs, we measured six common dialkylphosphate metabolites of OP pesticides in maternal urine, at two times during pregnancy (16 w & 26 w gestation), then calculated aggregate concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate metabolites. We measured infant neurobehavior at about five weeks of age using the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of neurobehavior in young infants. Analyses of associations between gestational exposure to OPs and neurobehavior at five weeks included multiple linear and logistic regression. RESULTS: After adjustment for covariates, higher creatinine-corrected urinary concentrations of diethylphosphate metabolites were associated with improved attention and reduced lethargy and hypotonia in young infants. Higher creatinine-corrected urinary concentrations of total dialkylphosphate metabolites were associated with fewer signs of autonomic stress. Women who were white, married, had advanced education, and reported more frequent consumption of fresh fruits and vegetables had higher concentrations of OP metabolites during pregnancy. CONCLUSIONS: In this sample of pregnant women whose urinary concentrations of dialkylphosphate metabolites are representative of national exposure levels, we found no detrimental effects of gestational exposure to OPs on neurobehavioral outcomes among young infants. These results are important as they suggest there may be minimal to no detectable adverse impact of low level prenatal OP exposure on the neurobehavior of young infants.

Maternal depression and prenatal exposure to methamphetamine: neurodevelopmental findings from the infant development, environment, and lifestyle (ideal) study.

BACKGROUND: Maternal depression is associated with a higher incidence of behavioral problems in infants, but the effects of maternal depression as early as 1 month are not well characterized. The objective of this study is to determine the neurobehavioral effects of maternal depression on infants exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS). METHODS: Four hundred twelve mother-infant pairs were enrolled (MA = 204) and only biological mothers with custody of their child were included in the current analysis. At the 1-month visit (n = 126 MA-exposed; n = 193 MA-unexposed), the Beck Depression Inventory-II (BDI-II) was administered, and the NNNS was administered to the infant. Exposure was identified by self-report and/or gas chromatography/mass spectroscopy confirmation of amphetamine and metabolites in newborn meconium. Unexposed subjects were matched, denied amphetamine use, and had negative meconium screens. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS, with significance accepted at P < .05. RESULTS: The MA group had an increased incidence of depression-positive diagnosis and increased depression scores on the BDI-II. After adjusting for covariates, MA exposure was associated with increased arousal and handling scores, and a decreased ability to self-regulate. Maternal depression was associated with higher autonomic stress and poorer quality of movement. No additional differences were observed in infants whose mothers were both depressed and used MA during pregnancy. CONCLUSIONS: Maternal depression is associated with neurodevelopmental patterns of increased stress and decreased quality of movement, suggesting maternal depression influences neurodevelopment in infants as young as 1 month.

Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos developmental neurobehavioral outcomes.

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring.

Child neurodevelopment in a Bolivian mining city.

This study evaluates the neurodevelopment of children living near contaminated mining industries during their first year of life. Participants from the city of Oruro (Bolivia) were prospectively recruited during pregnancy. Follow-up occurred between May 2007 and November 2009. Information about the socioeconomic status and medical history of the pregnant women were collected using questionnaires. Neurodevelopment was evaluated for 246 children using the Bayley Scales of Infant Development (BSID) at 10.5-12.5 months of age. Exposure to trace elements (Pb, As, Cd, Sb, Cs, Zn, Fe, Cu, Se, Rb, and Sr) during prenatal life was evaluated by testing maternal blood concentrations before delivery. Almost all measured levels were lower than the control limits. The blood lead concentration of pregnant women was low, considering the contaminated environmental context. The geometric mean was 1.76 µg/dL (95% CI: 1.68-1.84), a level comparable with those observed in non-contaminated areas. The only element found to be relatively elevated was antimony, with a geometric mean of 1.03 µg/dL (95% CI: 0.96-1.11). Our results suggest that women from this mining area were not highly exposed. The Bayley Scales of Infant Development (BSID) did not reveal mental or psychomotor abnormalities. Surprisingly, at the observed low levels, lead was positively associated with the children's BSID performance.