Neonatal Neurobehavior Research Articles

The effect of xenon on fetal neurodevelopment following maternal sevoflurane anesthesia and laparotomy in rabbits

BackgroundThere is concern that maternal anesthesia during pregnancy impairs brain development of the human fetus. Xenon is neuroprotective in pre-clinical models of anesthesia-induced neurotoxicity in neonates. It is not known if xenon also protects the developing fetal brain when administered in addition to maternal sevoflurane-anesthesia during pregnancy. ObjectiveTo investigate the effects of sevoflurane and xenon on neurobehaviour and neurodevelopment of the offspring in a pregnant rabbit model. MethodsPregnant rabbits on post-conception day 28 (term = 31d) underwent two hours of general anesthesia with 1 minimum alveolar concentration (MAC) of sevoflurane in 30% oxygen (n = 17) or 1 MAC sevoflurane plus 50-60 % xenon in 30% oxygen (n = 10) during a standardized laparotomy while receiving physiological monitoring. A sham-group (n = 11) underwent monitoring alone for two hours. At term, the rabbits were delivered by caesarean section. On the first postnatal day, neonatal rabbits underwent neurobehavioral assessment using a validated test battery. Following euthanasia, the brains were harvested for neurohistological analysis. A mixed effects-model was used for statistical analysis. ResultsMaternal cardiopulmonary parameters during anesthesia were within the reference range. Fetal survival rates were significantly higher in the sham-group as compared to the sevoflurane-group and the fetal brain/body weight ratio was significantly lower in the sevoflurane-group as compared with the sham- and xenon-group. Pups antenatally exposed to anesthesia had significantly lower motor and sensory neurobehavioral scores when compared to the sham-group (mean ± SD; sevo: 22.70 ± 3.50 vs. sevo+xenon: 22.74 ± 3.15 vs. sham: 24.37 ± 1.59; overall p = 0.003; sevo: 14.98 ± 3.00 vs. sevo+xenon: 14.80 ± 2.83 vs. sham: 16.43 ± 2.63; overall p = 0.006; respectively). Neuron density, neuronal proliferation and synaptic density were reduced in multiple brain regions of the exposed neonates. The co-administration of xenon had no measurable neuroprotective effects in this model. ConclusionsIn rabbits, sevoflurane anesthesia for a standardized laparotomy during pregnancy resulted in impaired neonatal neurobehavior and a decreased neuron count in several regions of the neonatal rabbit brain. Co-administration of xenon did not prevent this effect.

Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants

BackgroundInfants born very preterm are more likely to experience neonatal morbidities compared to their term peers. Variations in DNA methylation (DNAm) associated with these morbidities may yield novel information about the processes impacted by these morbidities.MethodsThis study included 532 infants born < 30 weeks gestation, participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants study. We used a neonatal morbidity risk score, which was an additive index of the number of morbidities experienced during the NICU stay, including bronchopulmonary dysplasia (BPD), severe brain injury, serious neonatal infections, and severe retinopathy of prematurity. DNA was collected from buccal cells at discharge from the NICU, and DNAm was measured using the Illumina MethylationEPIC. We tested for differential methylation in association with the neonatal morbidity risk score then tested for differentially methylated regions (DMRs) and overrepresentation of biological pathways.ResultsWe identified ten differentially methylated CpGs (α Bonferroni-adjusted for 706,278 tests) that were associated with increasing neonatal morbidity risk scores at three intergenic regions and at HPS4, SRRD, FGFR1OP, TNS3, TMEM266, LRRC3B, ZNF780A, and TENM2. These mostly followed dose–response patterns, for 8 CpGs increasing DNAm associated with increased numbers of morbidities, while for 2 CpGs the risk score was associated with decreasing DNAm. BPD was the most substantial contributor to differential methylation. We also identified seven potential DMRs and over-representation of genes involved in Wnt signaling; however, these results were not significant after Bonferroni adjustment for multiple testing.ConclusionsNeonatal DNAm, within genes involved in fibroblast growth factor activities, cellular invasion and migration, and neuronal signaling and development, are sensitive to the neonatal health complications of prematurity. We hypothesize that these epigenetic features may be representative of an integrated marker of neonatal health and development and are promising candidates to integrate with clinical information for studying developmental impairments in childhood.

Epigenome-wide analysis identifies genes and pathways linked to acoustic cry variation in preterm infants

BackgroundPreterm birth places infants at higher risk of adverse long-term behavioral and cognitive outcomes. Combining biobehavioral measures and molecular biomarkers may improve tools to predict risk of long-term developmental delays.MethodsThe Neonatal Neurobehavior and Outcomes in Very Preterm Infants study was conducted at 9 neonatal intensive care units between April 2014 and June 2016. Cries were recorded and buccal swabs collected during the neurobehavioral exam. Cry episodes were extracted and analyzed using a computer system the data were summarized using factor analysis. Genomic DNA was extracted from buccal swabs, quantified using the Quibit Fluorometer, and aliquoted into standardized concentrations. DNA methylation was measured with the Illumina MethylationEPIC BeadArray, and an epigenome-wide association study (EWAS) was performed using cry-factors (n=335).ResultsEighteen CpGs were associated with the cry factors at genome-wide significance (α=7.08E-09). Two CpG sites, one intergenic and one linked to gene TCF3 (important for B and T lymphocyte development), were associated with acoustic measures of cry energy. Increased methylation of TCF3 was associated with a lower energy-related cry factor. We also found that pitch (F0) and hyperpitch (F0 > 1kHz) were associated with DNA methylation variability at 16 CpG sites.ConclusionsAcoustic cry characteristics are related to variation in DNA methylation in preterm infants.

Sociodemographic and medical influences on neurobehavioral patterns in preterm infants: A multi-center study

BackgroundAmong preterm infants, neurodevelopmental outcomes are influenced by both medical and sociodemographic factors. Less is known about the impact on these factors on neonatal neurobehavioral patterns. ObjectiveTo determine associations between demographic, psychosocial and medical risk factors and neonatal neurobehavior. MethodsMulti-center observational study of infants born <30 weeks enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study between April 2014–May 2016. Maternal medical, demographic, and psychological variables and infant medical variables were prospectively collected. Demographic, substance, psychological and medical risk indices were developed. Neurobehavioral assessment was performed using the NICU Network Neurobehavioral Scale (NNNS) at NICU discharge. Results709 infants were enrolled in the NOVI study, and for 679 infants with neurobehavioral assessments, 6 NNNS behavioral profiles were calculated using latent profile analysis. Profile 6 infants (n = 47/679, 7%) were atypical, having poor attention, self-regulation and movement quality, hypertonia and increased stress signs. After adjustment for site, profile 6 infants had significantly smaller head circumferences at birth (β −0.87; −1.59, −0.14), and higher rates of late sepsis (OR 3.38; CI 1.66, 6.92) compared to Profiles 1–5 infants. There were no significant differences in other neonatal morbidities between the two groups. Profile 6 infants had a higher prenatal demographic risk score (1.46 vs 1.07;β 0.34; CI 0.06, 0.61) compared to Profiles 1–5 infants. ConclusionNNNS behavioral profiles identify an atypical behavioral pattern that is associated with early influences of demographic and medical variables. Such behavioral patterns may be seen as early as NICU discharge.

Psychosocial and medical adversity associated with neonatal neurobehavior in infants born before 30 weeks gestation.

Background:Psychosocial adversity escalates medical risk for poor outcomes in infants born <30 weeks’ gestation. Neonatal neurobehavior and maternal psychological and socioenvironmental assessments may identify the earliest specific intervention needs. We hypothesized that maternal prenatal anxiety, depression, and adverse medical and socioenvironmental conditions would be associated with less optimal neonatal neurobehavior at NICU discharge.Methods:We studied 665 infants at 9 university NICUs. Risk indices of socioenvironmental, maternal, and neonatal medical factors were obtained from standardized, structured maternal interviews and medical record reviews. Brain injuries were classified by consensus ultrasonogram readings. NICU Network Neurobehavioral Scale (NNNS) exams were conducted at NICU discharge.Results:On the NNNS, generalized estimating equations indicated infants of mothers with prenatal anxiety had less optimal attention, and those born to mothers with prenatal depression had increased lethargy. Maternal medical complications predicted suboptimal reflexes. Socioenvironmental risk predicted lower self-regulation and movement quality. Infants with more severe neonatal medical complications had lower attention, increased lethargy, and suboptimal reflexes.Conclusions:Combined information from the observed associations among adverse prenatal maternal medical and psychosocial conditions, and neonatal complications may assist in the early identification of infants at elevated neurobehavioral risk.

Global and Regional Changes in Cortical Development Assessed by MRI in Fetuses with Isolated Nonsevere Ventriculomegaly Correlate with Neonatal Neurobehavior.

Fetuses with isolated nonsevere ventriculomegaly (INSVM) are at risk of presenting neurodevelopmental delay. However, the currently used clinical parameters are insufficient to select cases with high risk and determine whether subtle changes in brain development are present and might be a risk factor. The aim of this study was to perform a comprehensive evaluation of cortical development in INSVM by magnetic resonance (MR) imaging and assess its association with neonatal neurobehavior. Thirty-two INSVM fetuses and 29 healthy controls between 26-28 weeks of gestation were evaluated using MR imaging. We compared sulci and fissure depth, cortical maturation grading of specific areas and sulci and volumes of different brain regions obtained from 3D brain reconstruction of cases and controls. Neonatal outcome was assessed by using the Neonatal Behavioral Assessment Scale at a mean of 4 ± 2 weeks after birth. Fetuses with INSVM showed less profound and underdeveloped sulcation, including the Sylvian fissure (mean depth: controls 16.8 ± 1.9 mm, versus INSVM 16.0 ± 1.6 mm; P = .01), and reduced global cortical grading (mean score: controls 42.9 ± 10.2 mm, versus INSVM: 37.8 ± 9.9 mm; P = .01). Fetuses with isolated nonsevere ventriculomegaly showed a mean global increase of gray matter volume (controls, 276.8 ± 46.0 ×10 mm3, versus INSVM 277.5 ± 49.3 ×10 mm3, P = .01), but decreased mean cortical volume in the frontal lobe (left: controls, 53.2 ± 8.8 ×10 mm3, versus INSVM 52.4 ± 5.4 ×10 mm3; P = < .01). Sulcal depth and brain volumes were significantly associated with the Neonatal Behavioral Assessment Scale severity (P = .005, Nagelkerke R2 = 0.732). INSVM fetuses showed differences in cortical development, including regions far from the lateral ventricles, that are associated with neonatal neurobehavior. These results suggest the possible use of these parameters to identify cases at higher risk of altered neurodevelopment.

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in buccal cell DNA methylation (DNAm) associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N = 536). We tested whether epigenetic age, age acceleration, or DNAm levels at individual loci differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (β1 = 0.201, p-value = 0.026), but no significant difference in age acceleration. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Some of the genes annotated to these CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders. These findings contribute to the existing evidence that neonatal epigenetic variations may be informative for infant neurobehavior.

Early developmental trajectories of preterm infants

Background and objectivesPreterm infants are at risk for neuro-developmental impairments and atypical developmental trajectories. The aims of this study were to delineate early developmental trajectories of preterm and full-term infants. MethodsThe cognitive, language, and motor development of 149 infants – 19 extremely preterm (EPT), 34 very preterm (VPT), 57 moderately preterm (MPT), and 39 full-term (FT) – was evaluated using Mullen Scales at 1, 4, 8, 12, and 18 months. Mixed models were applied to examine group differences. Gender, maternal education, and neurobehavior were included as predictors of developmental trajectories. ResultsThe EPT and VPT infants achieved significantly lower scores than the FT infants in all domains, with a significantly increasing gap over time. The MPT infants' trajectories were more favorable than those of the EPT and VPT infants yet lower than the FT infants on the Visual Reception, Gross, and Fine Motor subscales. Male gender and lower maternal education were associated with lower scores that declined over time. Abnormal neonatal neurobehavior was associated lower Mullen scores and with less stability in scores over time. ConclusionsThe EPT and VPT infants were found to have disadvantages across all domains. The MPT infants revealed more favorable developmental trajectories yet displayed vulnerability compared to the FT infants. Gender, maternal education, and neonatal neurobehavior are important in predicting the developmental outcomes of preterm infants.

Defining the nature and implications of head turn preference in the preterm infant

AimTo determine the relationship of head turn preference in the preterm infant to: 1) perinatal medical factors, 2) neonatal neurobehavior, and/or 3) infant neurodevelopmental outcomes. MethodsSeventy preterm infants born ≤30weeks gestation were enrolled at birth. Detailed information regarding neonatal intensive care unit (NICU) medical course was compiled for each infant. Neurobehavioral testing was performed during NICU hospitalization. Head turn preference was quantified at term equivalent age using a newly developed scale. Infants returned at age two years for standardized developmental testing. ResultsAll infants demonstrated a head turning preference, with most preferring the right side (n=51, 77%). Fifty-five infants (79%) had moderate to severe head turn preference. Head turn preference was associated with 1) medical severity (hours of inotrope use, p=0.02; oxygen requirement at 36weeks postmenstrual age, p=0.03), 2) worse neurobehavioral performance (decreased self-regulation, p=0.007; more sub-optimal reflexes p=0.006), and 3) worse developmental outcome at age two years (poorer fine motor, p=0.02). InterpretationMedical factors in the NICU appear to be associated with the development of a head turn preference. Increased severity of head turn preference may be a marker for poor developmental outcome. Early identification may inform therapeutic interventions designed to minimize symptoms and optimize neurodevelopmental outcome.

Alcohol exposure in utero is associated with decreased gray matter volume in neonates.

Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions. However, the temporal specificity of such changes and their behavioral consequences are less known. Here we explore the brain structure of infants with in utero exposure to alcohol shortly after birth. T2 structural MRI images were acquired from 28 alcohol-exposed infants and 45 demographically matched healthy controls at 2-4 weeks of age on a 3T Siemens Allegra system as part of large birth cohort study, the Drakenstein Child Health Study (DCHS). Neonatal neurobehavior was assessed at this visit; early developmental outcome assessed on the Bayley Scales of Infant Development III at 6 months of age. Volumes of gray matter regions were estimated based on the segmentations of the University of North Carolina neonatal atlas. Significantly decreased total gray matter volume was demonstrated for the alcohol-exposed cohort compared to healthy control infants (p < 0.001). Subcortical gray matter regions that were significantly different between groups after correcting for overall gray matter volume included left hippocampus, bilateral amygdala and left thalamus (p < 0.01). These findings persisted even when correcting for infant age, gender, ethnicity and maternal smoking status. Both early neurobehavioral and developmental adverse outcomes at 6 months across multiple domains were significantly associated with regional volumes primarily in the temporal and frontal lobes in infants with prenatal alcohol exposure. Alcohol exposure during the prenatal period has potentially enduring neurobiological consequences for exposed children. These findings suggest the effects of prenatal alcohol exposure on brain growth is present very early in the first year of life, a period during which the most rapid growth and maturation occurs.

Neurobehavioral evaluation in the preterm and term infant.

Neurobehavioral examinations of babies, both term and preterm, have been used in neonatology for many decades. However, with the advent of new technologies and, perhaps more "scientific" ways of assessing high risk infants, it seems that neurobehavioral examinations may have become somewhat redundant in some nurseries. Yet these examinations remain an important part of clinical practice. They help to increase our understanding of an infant's behavior, including their strengths and vulnerabilities, thus enabling us to adjust our care and parent education accordingly. These examinations also assist us to identify those most at risk of developmental disabilities, enabling further assessment and intervention to be considered as early as possible. Whilst it remains a challenge to try and quantify neonatal neurobehavior, there are numerous tools available that can greatly assist us. This review did not find a tool that served all populations and all assessment purposes. Consequently, the clinician or researcher needs to choose the appropriate assessment depending on matters such as the infant's gestation and the assessment's goal and training requirements. Further research is needed to develop neurobehavioral assessment tools, particularly for extremely preterm infants, which are easily accessible in the clinical setting and can be used from birth.

Perinatal factors influencing neonatal behavioral neurological assessment

Objective To investigate the neonatal neurobehavioral ability and the associated perinatal factors.Methods 298 neonatal term infants were assessed by neonatal behavioral neurological assessment(NBNA) which was established by Bao Xiulan.The information of the neonatal babies and their family was investigated by the self-made basic information questionnaire.Logistic regression analysis was used to screen the influencing factors with NBNA scores as dependent variable and 19 perinatal factors as independent variables.Results:99.33％ neonates got through NBNA.Gestational weeks and emotion during pregnancy were positive factors whose partial regression coefficients were-0.41 and-0.33.The ages of pregnant women was negative factors in neonates' NBNA.Conclusions More gestational weeks and better mood during pregnancy can promote and higher ages of the pregnant women can negatively influence the development of neonatal neurobehavior. Key words: Neonate; Neurobehavior; Perinatal; Logistic regression model

Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI

We tested the hypothesis whether small-for-gestational-age (SGA) fetuses have different brain stem and cerebellar morphometry when compared with appropriate-for-gestational-age (AGA) fetuses and whether the differences in these structures were associated with their neonatal neurobehavior. Magnetic resonance imaging was performed on 51 SGA fetuses and 47 AGA fetuses at 37 weeks' gestation. Pontine width, medullar width, vermian width and height, cerebellar primary fissure's depth, and cerebellar volume were measured and corrected by biparietal diameter and cerebellar volume by total intracranial volume. Ratios were compared between cases and control subjects. The association between morphometric differences and neurobehavioral outcome in SGAs was tested. Brainstem and cerebellar ratios were significantly larger in SGA fetuses: pontine width, SGA 0.143 ± 0.01 vs AGA 0.135 ± 0.01 (P < .01); medullar width, SGA 0.088 ± 0.01 vs AGA 0.083 ± 0.01 (P = .03); vermian width, SGA 0.181 ± 0.03 vs AGA 0.162 ± 0.02 (P < .01); vermian height, SGA 0.235 ± 0.03 vs AGA 0.222 ± 0.01 (P < .01); cerebellar volume, SGA 0.042 ± 0.01 vs AGA 0.038 ± 0.00 (P = .04); with deeper cerebellar primary fissure in SGAs, SGA 0.041 ± 0.01 vs AGA 0.035 ± 0.01 (P = .01). Medullar, cerebellar biometries, and volumetry were significantly associated with different Neonatal Behavioral Assessment Scale cluster scores in SGA infants. Brain stem and cerebellar morphometric measurements are significantly different in term SGA fetuses, which are associated significantly with their neurobehavioral outcome. This finding supports the existence of brain microstructural changes in SGA fetuses and lays the basis for potential image biomarkers to detect fetuses who are at risk.

Depression during gestation in adolescent mothers interferes with neonatal neurobehavior

To compare the neurobehavior of neonates born to adolescent mothers with and without depression during gestation. This prospective cross-sectional study included healthy term neonates born to adolescent mothers with untreated depression during gestation, without exposure to legal or illicit drugs, and compared them with infants born to adolescent mothers without psychiatric disorders. Maternal psychiatric diagnoses were assessed by the Composite International Diagnostic Interview (CIDI 2.1) and neonatal neurobehavior by the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) at 24 to 72 hours of life. Neurobehavioral outcomes were analyzed by ANOVA adjusted for confounders. 37 infants born to mothers with depression during gestation were compared to 332 infants born to mothers without psychiatric disorders. Infants of mothers with depression had smaller head circumferences. Significant interactions of maternal depression and male gender, gestational age > 40 weeks, regional anesthesia during delivery, vaginal delivery, and infant head circumference ≥ 34 cm were found. Worse performance was noted in the following neonatal neurobehavioral parameters: arousal, excitability, lethargy, hypotonicity, and signs of stress and abstinence. Infants born to adolescent mothers with depression exhibit some behavioral changes in the first days of life. These changes are associated with infant sex, gestational age, type of anesthesia, mode of delivery, and head circumference.

Neurobehavior of term neonates with neonatal hyperbilirubinemia

Objective:To find the effect of neonatal hyperbilirubinemia on neurobehavior of term infants.Materials and Methods:This study was undertaken in the neonatal unit of our tertiary care hospital. Term neonates who developed jaundice with serum bilirubin value of above 15 mg/dl within 1st week of life were enrolled in the study. Peak total serum bilirubin (PSB) levels of cases were recorded. Age and sex matched normal controls were assigned to every case. Both the groups were assessed by Brazelton′s neurobehavioral assessment scale (NBAS) and the scores of the individual clusters were compared.Results:Habituation, range of state, autonomic regulation and regulation of state clusters were significantly altered in the case group, while motor organization cluster was mainly affected in neonates with severe jaundice (PSB > 25 mg/dl). No differences were noted in the reflex and orientation NBAS clusters.Conclusion:Neonatal hyperbilirubinemia causes definite alteration in the neonatal neurobehavior.

Neonatal neurobehavior effects following buprenorphine versus methadone exposure.

To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior. Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy. Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria. Thirty-nine full-term infants. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30. While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03). While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.

Bisphenol A and Infant Neonatal Neurobehavior

Bisphenol A and Infant Neonatal Neurobehavior

A longitudinal study on the effects of maternal smoking and secondhand smoke exposure during pregnancy on neonatal neurobehavior

Maternal smoking during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant women and their fetuses. The long-term effects of prenatal exposure to smoke on child behavior and development have been the subject of more extensive research than have the short-term effects. Therefore, the aim of this work is to examine the effects of smoke exposure during pregnancy on neonatal behavior, including in our study a group of mothers exposed to secondhand smoke. The behavior of 282 healthy full-term newborns was assessed using the Neonatal Behavior Assessment Scale (NBAS) at 48–72h of life. Sixty-two mothers smoked during pregnancy (no mother smoked more than 15cig/day) and 17 were exposed to secondhand smoke. After adjusting for socio-demographic and obstetric factors, both newborns whose mothers smoked and those whose mothers were exposed to secondhand smoke showed significantly lower scores in the habituation cluster than non-smoking mothers. Exposure to secondhand smoke was also related to lower motor system cluster scores as well as some supplementary items and the newborns of smoking mothers showed significantly lower scores in the state regulation cluster and in some items of the state organization cluster than the newborns of non-smoking mothers. We conclude that active and passive smoking during pregnancy affects several aspects of neurobehavioral development, regardless of socio-demographic, obstetric and pediatric factors.

GSTM1 Modifies the Effect of Maternal Exposure to Environmental Tobacco Smoke on Neonatal Primitive Reflexes

The aim of this study was to examine whether infant metabolic gene polymorphisms modify the effect of maternal environmental tobacco smoke (ETS) on neonatal neurobehavior. We conducted a birth cohort study of 87 nonsmoking women who delivered single births of normal birth weight. We enrolled the women before delivery, interviewed them using a structured questionnaire, and collected umbilical cord blood. Umbilical cord cotinine, a blood indicator of prenatal ETS exposure, was analyzed. The Neonatal Neurobehavioral Examination-Chinese Version (NNE-C) was administrated within 5 days after delivery to examine neonatal neurobehavior. Four infant metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1, and GSTM1, were identified. Maternal ETS exposure during pregnancy was not related to neonatal neurobehavior when infant genetic polymorphisms were not considered. However, maternal ETS exposure did cause adverse effects in neonates with the absent type of GSTM1. Adverse effects were seen on the total NNE-C (β = -2.55; p = .02) and on primitive reflexes (β = -1.70; p = .004), especially in grasp reflexes (β = -.36; p = .011) and tonic neck reflexes (β = -.36; p = .049). In addition, there was a significant interaction between maternal ETS exposure and infant GSTM1 genotype on neonate grasp reflexes (p for interaction = .019). These data indicate that weaker responses in neonatal primitive reflexes in infants with the absent type GSTM1 were related to maternal ETS exposure during pregnancy.

Neurobehavioral outcomes in preterm, growth‐restricted infants with and without prenatal advanced signs of brain‐sparing

To evaluate the neurobehavioral outcomes of preterm infants with intrauterine growth restriction (IUGR), with and without prenatal advanced brain-sparing. A cohort of IUGR infants (birth weight < 10(th) percentile with abnormal umbilical artery Doppler) born before 34 weeks of gestation was compared with a control group of appropriate-for-gestational age infants matched for gestational age at delivery. MCA pulsatility index was determined in all cases within 72 hours before delivery. Neonatal neurobehavior was evaluated at 40 weeks' ( ± 1) corrected age using the Neonatal Behavioral Assessment Scale. The effect of abnormal MCA pulsatility index (< 5(th) percentile) on each neurobehavioral area was adjusted for maternal smoking status and socioeconomic level, mode of delivery, gestational age at delivery, pre-eclampsia, newborn illness severity score and infant sex by multiple linear and logistic regression. A total of 126 preterm newborns (64 controls and 62 IUGR) were included. Among IUGR fetuses, the proportion of abnormal MCA Doppler parameters was 53%. Compared with appropriate-for-gestational age infants, newborns in the IUGR subgroup with abnormal MCA Doppler had significantly lower neurobehavioral scores in the areas of habituation, motor system, social-interactive and attention. Similarly, the proportion of infants with abnormal neurobehavioral scores was significantly higher in the IUGR subgroup with abnormal MCA Doppler parameters in the areas of habituation, social-interactive, motor system and attention. Abnormal MCA Doppler findings are predictive of neurobehavioral impairment among preterm newborns with IUGR, which suggests that this reflects an advanced stage of brain injury with a higher risk of abnormal neurological maturation.