Effects of 1.5-T versus 3-T magnetic resonance imaging in fetuses: is there a difference in postnatal neurodevelopmental outcome? Evaluation in a fetal population with left-sided congenital diaphragmatic hernia.

BACKGROUND: The utilization of 3-T magnetic field strength in obstetric imaging is increasingly common. It is important to ensure that magnetic resonance (MR) imaging with higher magnetic field strength is safe for the fetus. Comparison of neurodevelopmental outcome in neonates undergoing prenatal MR imaging with 1.5-T versus 3-T is of interest but has not yet been examined. OBJECTIVE: We hypothesized no clinically meaningful difference in neurodevelopmental outcome between fetuses undergoing 1.5-T versus 3-T fetal MR imaging. As imaging a normal fetus for research purposes is illegal in Pennsylvania, this study was conducted in a population of fetuses with left congenital diaphragmatic hernia (left-CDH). MATERIALS AND METHODS: A retrospective review of neurodevelopmental outcome of fetuses with left-CDH scanned at 1.5-T (n=75) versus 3-T (n=25) magnetic field strength between July of 2012 and December of 2019 was performed. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). RESULTS: There were no statistical differences in median age of assessment (1.5-T: 18 [12, 25] versus 3-T: 21 [11, 26], P=0.79), in mean BSID-III cognitive (1.5-T: 91 ± 14 versus 3-T: 90 ± 16, P=0.82), language (1.5-T: 92 ± 20 versus 3-T: 91 ± 20, P=0.91), and motor composite (1.5-T: 89 ± 15 versus 3-T: 87 ± 18, P=0.59) scores, subscales scores (for all, P>0.50), or in risk of abnormal neuromuscular exam (P=0.29) between neonates with left-CDH undergoing a 1.5-T versus 3-T MR imaging during fetal life. Additionally, the distribution of patients with average, mildly delayed, and severely delayed BSID-III scores was similar between the two groups (for all, P>0.50). The overall distribution of the composite scores in this CDH population was similar to the general population independent of exposure to 1.5-T or 3-T fetal MR imaging. Two 3-T patients (8%) and five 1.5-T patients (7%) scored within the significant delayed range for all BSID-III domains. Subjects with lower observed-to-expected fetal lung volume (O/E FLV) and postnatal need for ECMO had lower cognitive, language, motor, and subscales scores (for all, P<0.03) regardless of being imaged at 1.5-T versus 3-T. CONCLUSION: This preliminary study suggests that, compared to 1.5-T MR imaging, fetal exposure to 3-T MR imaging does not increase the risk of neurodevelopmental impairment in fetuses with left-CDH. Additional MR imaging studies in larger CDH cohorts and other fetal populations are needed to replicate and extend the present findings.

The associations of prenatal exposure to dioxins and polychlorinated biphenyls with neurodevelopment at 6 Months of age: Multi-pollutant approaches.

BACKGROUND: Prenatal exposure to persistent organic pollutants, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs), and nondioxin-like PCBs (NDL-PCBs), has been hypothesized to have a detrimental impact on neurodevelopment. However, the association of prenatal exposure to a dioxin and PCB mixture with neurodevelopment remains largely inconclusive partly because these chemical levels are correlated. OBJECTIVES: We aimed to elucidate the association of in utero exposure to a mixture of dioxins and PCBs with neurodevelopment measured at 6 months of age by applying multipollutant methods. METHODS: A total of 514 pregnant women were recruited between July 2002 and October 2005 in the Sapporo cohort, Hokkaido Study on Environment and Children's Health. The concentrations of individual dioxin and PCB isomers were assessed in maternal peripheral blood during pregnancy. The mental and psychomotor development of the study participants' infants was evaluated using the Bayley Scales of Infant Development-2nd Edition (n = 259). To determine both the joint and individual associations of prenatal exposure to a dioxin and PCB mixture with infant neurodevelopment, Bayesian kernel machine regression (BKMR) and quantile-based g-computation were employed. RESULTS: Suggestive inverse associations were observed between in utero exposure to a dioxin and PCB mixture and infant psychomotor development in both the BKMR and quantile g-computation models. In contrast, we found no association of a dioxin and PCB mixture with mental development. When group-specific posterior inclusion probabilities were estimated, BKMR suggested prenatal exposure to mono-ortho PCBs as the more important contributing factors to early psychomotor development compared with the other dioxin or PCB groups. No evidence of nonlinear exposure-outcome relationships or interactions among the chemical mixtures was detected. CONCLUSIONS: Applying the two complementary statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and PCBs with infant psychomotor development.

DHA supplementation in infants born preterm and the effect on attention at 18 months' corrected age: follow-up of a subset of the N3RO randomised controlled trial.

Infants born preterm miss out on the peak period of in utero DHA accretion to the brain during the last trimester of pregnancy which is hypothesised to contribute to the increased prevalence of neurodevelopmental deficits in this population. This study aimed to determine whether DHA supplementation in infants born preterm improves attention at 18 months' corrected age. This is a follow-up of a subset of infants who participated in the N3RO randomised controlled trial. Infants were randomised to receive an enteral emulsion of high-dose DHA (60 mg/kg per d) or no DHA (soya oil - control) from within the first days of birth until 36 weeks' post-menstrual age. The assessment of attention involved three tasks requiring the child to maintain attention on toy/s in either the presence or absence of competition or a distractor. The primary outcome was the child's latency of distractibility when attention was focused on a toy. The primary outcome was available for seventy-three of the 120 infants that were eligible to participate. There was no evidence of a difference between groups in the latency of distractibility (adjusted mean difference: 0·08 s, 95 % CI -0·81, 0·97; P = 0·86). Enteral DHA supplementation did not result in improved attention in infants born preterm at 18 months' corrected age.

Do NICU developmental care improve cognitive and motor outcomes for preterm infants? A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to review the effects of developmental care in neonatal intensive care unit (NICU) setting on mental and motor development of preterm infants. METHOD: We searched PubMed, EMBASE, CINAHL, Scopus, Web of Science and Cochrane library until October 8th 2017, and included randomized controlled trials that assessed effects of developmental care in NICU on mental and motor development of preterm infants at 12 and 24 months of age, using the Bayley scale of infant development in this systematic review. In addition, data were pooled by random effects model and Standardized Mean Difference (SMD) with 95% confidence intervals (CI), calculated for meta-analysis. RESULTS: Twenty one studies were eligible to be included in this systematic review; however, only thirteen studies had data suitable for meta-analysis. According to statistical analysis, developmental care in NICU improved mental developmental index (MDI) (standardized mean difference [SMD] 0.55, 95% confidence interval [CI] 0.23-0.87; p < 0.05), and psychomotor developmental index (PDI) (SMD 0.33, [CI] 95% CI 0.08-0.57; p < 0.05) of BSID at 12 months of age and PDI at 24 months of age (SMD 0.15, 95% CI -0.02-0.32; p < 0.1) of preterm infants. However, the benefit was not detected at 24 months of age on MDI (SMD 0.15, 95% CI -0.05-0.35; p = 0.15). CONCLUSION: Current evidence suggests that developmental care in only NICU setting could have significant effect on mental and motor development of preterm infants, especially at 12 months of age. However, because of clinical heterogeneity, more studies are needed to evaluate the effects of developmental NICU care in the development of preterm infants.

Early Movement Matters: Interplay of Physical Activity and Motor Skill Development in Infants With Down Syndrome.

This longitudinal study investigated monthly motor development and physical activity (PA) of infants with and without Down syndrome. Gross and fine motor skills (Bayley Scales of Infant Development-III) and PA (accelerometer) were assessed in 35 infants at eight time points during infancy. A multivariate mixed model identified time points when motor scores diverged between the groups. In infants with Down syndrome, bivariate correlations between monthly PA and motor changes were calculated, and multivariate analysis of variance probed the influence of early PA on motor-skill timing. Results indicate that differences in gross and fine motor skills first emerge at 2 and 4 months, respectively. In infants with Down syndrome, gross motor and PA changes between 4 and 6 months were positively correlated. Infants more active than the mean at 2 or 3 months achieved several prone and sitting skills earlier. These results highlight the adaptability of early infancy and the importance of early intervention.

Gastrostomy Tube Feeding in Extremely Low Birthweight Infants: Frequency, Associated Comorbidities, and Long-term Outcomes.

OBJECTIVE: To assess the frequency of gastrostomy tube (GT) placement in extremely low birth weight (ELBW) infants, associated comorbidities, and long-term outcomes. STUDY DESIGN: Analysis of ELBW infants from 25 centers enrolled in the National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-up Registry from 2006 to 2012. Frequency of GT placement before 18-22 months, demographic and medical factors associated with GT placement, and associated long-term outcomes at 18-22 months of corrected age were described. Associations between GT placement and neonatal morbidities and long-term outcomes were assessed with logistic regression after adjustment for center and common co-variables. RESULTS: Of the 4549 ELBW infants included in these analyses, 333 (7.3%) underwent GT placement; 76% had the GT placed postdischarge. Of infants with GTs, 11% had birth weights small for gestational age, 77% had bronchopulmonary dysplasia, and 29% severe intraventricular hemorrhage or periventricular leukomalacia. At follow-up, 56% of infants with a GT had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems. After adjustment, small for gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, poor growth, and NDI were associated with GT placement. Thirty-two percent of infants with GTs placed were taking full oral feeds at follow-up. CONCLUSIONS: GT placement is common in ELBW infants, particularly among those with severe neonatal morbidities. GT placement in this population was associated with poor growth, NDI, and chronic respiratory and feeding problems at follow-up. The frequency of GT placement postneonatal discharge indicates the need for close nutritional follow-up of ELBW infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.

First steps to a clinical research unit for developmental research in paediatric cardiology: conception and progress of the LEADER project (Long Term Early Development Research) in CHD.

OBJECTIVE: We developed the Long-term Early Development Research (LEADER) project to investigate the development of children with CHD and/or after cardiopulmonary resuscitation. Both populations are at risk for delays in motor, cognitive, and language development. However, few studies to date have investigated the longitudinal development in these children. METHODS: To establish a clinical research unit, we planned three studies: a cross-sectional study in children after cardiopulmonary resuscitation (LEADER-REA Pilot Study), a longitudinal study in children after cardiopulmonary resuscitation, with a focus on evaluating various biomarkers as predictors for developmental outcome (LEADER-CPR study), and a longitudinal study in children with ventricular septal defect, tetralogy of Fallot, or transposition of the great arteries after cardiac surgery (LEADER-CHD study). RESULTS: Implementation of all three LEADER studies was successful and study protocols were conducted as planned. Findings from the LEADER-REA Pilot study have been recently published and data collection for both prospective trials is ongoing. Descriptive analysis of the first 20 assessments of the LEADER-CHD study showed no severe deficits in overall cognitive, motor, and language developments in the children. CONCLUSIONS: Children with CHD and/or after cardiopulmonary resuscitation are at risk for developmental delay. Therefore, a detailed developmental assessment is necessary as a pre-requisite for individual developmental support. Our LEADER project has been shown to be feasible in a clinical setting and is the first step towards the establishment of a clinical research unit in our clinic with a focus on longitudinal research.

Developmental Outcome in Infants with Cardiovascular Disease After Cardiopulmonary Resuscitation: A Pilot Study.

Unfavorable neurological outcome in children after cardiopulmonary resuscitation in infancy is frequent. However, few studies have investigated the development of these patients using comprehensive developmental tests and the feasibility of the Bayley Scales of Infant Development, 3rd Edition (BSID-III) has not been reported for this population. In this cross-sectional pilot study, we assessed the cognitive, language, and motor development in infants after cardiopulmonary resuscitation of ≥ 5 min with the BSID-III at the age of 12 or 24 months, depending on recruitment age. For analysis, 11 patients with in-hospital (n = 8) and out-of-hospital (n = 3) cardiac arrest were included. BSID-III results could not be quantified in three patients because of visual/hearing and/or motor impairment. In patients with quantifiable scores, 50.0% scored average in composite BSID-III scores, while the other 50.0% showed developmental delays, scoring distinctly below average. We conclude that the BSID-III is feasible for developmental assessment in the majority of the study population, but the use of instruments suitable for hearing/visually impaired and/or severely disabled infants is crucial to avoid biased results. Accurate characterization of developmental deficits is important to facilitate early identification and therapy of deficits.

Prenatal phthalate biomarker concentrations and performance on the Bayley Scales of Infant Development-II in a population of young urban children.

INTRODUCTION: Evidence suggests prenatal phthalate exposures may have neurodevelopmental consequences. Our objective was to investigate prenatal exposure to phthalates and cognitive development in a cohort of young urban children. MATERIALS AND METHODS: We recruited pregnant women in New York City from 1998 to 2002 and measured concentrations of nine phthalate metabolites in urine collected in late pregnancy. We administered a neurodevelopmental screening instrument, the Bayley Scales of Infant Development II (BSID-II), to children who returned for follow-up at approximately 24 months (n=276). We estimated associations between phthalate metabolite concentrations in maternal urine and BSID-II indices (Mental Development Index (MDI), Psychomotor Development Index (PDI)). RESULTS: We observed no associations between phthalate metabolite concentrations and performance on the MDI or PDI in boys and girls combined. We did, however, observe evidence of effect measure modification by sex. We observed several negative associations between metabolite concentrations and both MDI and PDI scores among girls, suggesting poorer performance across multiple metabolites, with estimates equal to a 2-3 point decrease in score per ln-unit increase in creatinine-standardized metabolite concentration. Conversely, we observed multiple weakly positive associations among boys, equal to a 1-2 point increase in score per ln-unit increase in metabolite concentration. The strongest associations were for the metabolites mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate, and mono(3-carboxylpropyl) phthalate (MCPP). CONCLUSIONS: Girls of mothers with higher urinary concentrations of MCPP and metabolites of dibutyl phthalates had lower MDI scores on the BSID-II. These same biomarker concentrations were often associated with improved scores among boys. We observed similar results for MnBP, MCPP, and MBzP on the PDI. Given the prevalence of phthalate exposures in reproductive aged women, the implications of potential neurotoxicity warrant further investigation.

Association between maternal intake of n-6 to n-3 fatty acid ratio during pregnancy and infant neurodevelopment at 6 months of age: results of the MOCEH cohort study.

BACKGROUND & AIMS: Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for infant neurodevelopment. The nutritional adequacy of dietary LC-PUFAs depends not only on the LC-PUFAs intake but also on the n-6 to n-3 fatty acid ratio (n-6/n-3 PUFAs). This study aimed to identify the association between the maternal dietary n-6/n-3 PUFAs and motor and cognitive development of infants at 6 months of age. METHODS: We used data from 960 participants in the Mothers and Children's Environmental Health (MOCEH) study, which is a multi-center prospective cohort study. Dietary intake of pregnant women was assessed by a one-day 24-h recall method. Food consumption of infants was estimated based on the volume of breast milk and weaning foods. The duration of each feed was used to estimate the likely volume of milk consumed. Dietary intake of infants at 6 months was also assessed by a 24-h recall method. Cognitive and motor development of infants at 6 months of age was assessed by the Korean Bayley scales of infant development edition II (BSID-II) including the mental developmental index (MDI) and the psychomotor developmental index (PDI). RESULTS: Maternal intakes of n-6/n-3 PUFAs and linoleic acid (LA)-to-α-linolenic acid (ALA) ratio (LA/ALA) were 9.7 ± 6.3 and 11.12 ± 6.9, respectively. Multiple regression analysis, after adjusting for covariates, showed that n-6/n-3 PUFAs was negatively associated with both the MDI (ß = -0.1674, P = 0.0291) and PDI (ß = -0.1947, P = 0.0380) at 6 months of age. These inverse associations were also observed between LA/ALA and both the MDI and PDI (MDI; ß = -0.1567; P = 0.0310, PDI; ß = -0.1855; P = 0.0367). Multiple logistic regression analysis, with the covariates, showed that infants whose mother's LA/ALA were ranked in the 2nd, 3rd, and 4th quartile were at approximately twice the risk with more than twice the risk of delayed performance on the PDI compared to the lowest quartile (1st vs. 2nd; OR = 2.965; 95% CI = 1.376 - 6.390, 1st vs. 3rd; OR = 3.047; 95% CI = 1.374 - 6.756 and 1st vs. 4th; OR = 2.551; 95% CI = 1.160 - 5.607). CONCLUSIONS: Both the maternal dietary n-6/n-3 PUFAs and LA/ALA intake were significantly associated with the mental and psychomotor development of infants at 6 months of age. Thus, maintaining low n-6/n-3 PUFAs and LA/ALA is encouraged for women during pregnancy.

Effect of Breastfeeding Duration on Cognitive Development in Infants: 3-Year Follow-up Study.

We investigated the association between breastfeeding and cognitive development in infants during their first 3 years. The present study was a part of the Mothers' and Children's Environmental Health (MOCEH) study, which was a multi-center birth cohort project in Korea that began in 2006. A total of 697 infants were tested at age 12, 24, and 36 months using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II). The use and duration of breastfeeding and formula feeding were measured. The relationship between breastfeeding and the mental development index (MDI) score was analyzed by multiple linear regression analysis. The results indicated a positive correlation between breastfeeding duration and MDI score. After adjusting for covariates, infants who were breastfed for ≥ 9 months had significantly better cognitive development than those who had not been breastfed. These results suggest that the longer duration of breastfeeding improves cognitive development in infants.

Manganese in teeth and neurodevelopment in young Mexican-American children.

INTRODUCTION: Manganese (Mn) is an essential nutrient but higher exposure has been associated with poorer neurodevelopment in children. METHODS: We measured Mn levels in prenatal (Mnpre) (n=197) and postnatal (Mnpost) dentin (n=193) from children's shed teeth using laser ablation inductively coupled plasma mass spectroscopy and examined the relationship with children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) on the Bayley Scales of Infant Development at 6, 12, and 24-months. We explored non-linear associations and interactions by sex, blood lead concentrations and maternal iron status during pregnancy. RESULTS: A two-fold increase of Mnpost levels in dentin was associated with small decreases in MDI at 6-months and 12-months of age. We also observed a non-linear relationship between Mnpost levels and PDI at 6-months. We found effect modification by sex for Mnpost levels and neurodevelopment at 6-months with stronger effects among girls for both MDI (-1.5 points; 95% Confidence Interval (CI): -2.4, -0.6) and PDI (-1.8 points; 95% CI: -3.3, -0.3). Girls whose mothers had lower hemoglobin levels experienced larger decreases in MDI and PDI associated with Mnpre levels than girls whose mothers had higher hemoglobin levels (pinteraction=0.007 and 0.09, respectively). We did not observe interactions with blood lead concentrations or any relationships with neurodevelopment at 24-months. CONCLUSIONS: Using Mn measurements in tooth dentin, a novel biomarker that provides prenatal and early postnatal levels, we observed negative transient associations between postnatal Mn levels and early neurodevelopment with effect modification by sex and interactions with prenatal hemoglobin.

Oxidative stress early in infancy and neurodevelopmental outcome in very low-birthweight infants.

BACKGROUND: Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants. METHODS: Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II. RESULTS: Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II. CONCLUSIONS: In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age.

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age.

Mother-infant self- and interactive contingency at four months and infant cognition at one year: A view from microanalysis.

Although a considerable literature documents associations between early mother-infant interaction and cognitive outcomes in the first years of life, few studies examine the contributions of contingently coordinated mother-infant interaction to infant cognitive development. This study examined associations between the temporal dynamics of the contingent coordination of mother-infant face-to-face interaction at 4 months and cognitive performance on the Bayley Scales of Infant Development at age one year in a sample of (N = 100) Latina mother-infant pairs. Split-screen videotaped interactions were coded on a one second time base for the communication modalities of infant and mother gaze and facial affect, infant vocal affect, and mother touch. Multi-level time-series models evaluated self- and interactive contingent processes in these modalities and revealed 4-month patterns of interaction associated with higher one-year cognitive performance, not identified in prior studies. Infant and mother self-contingency, the moment-to-moment probability that the individual's prior behavior predicts the individual's future behavior, was the most robust measure associated with infant cognitive performance. Self-contingency findings showed that more varying infant behavior was optimal for higher infant cognitive performance, namely, greater modulation of negative affect; more stable maternal behavior was optimal for higher infant cognitive performance, namely, greater likelihood of sustaining positive facial affect. Although interactive contingency findings were sparse, they showed that, when mothers looked away, or dampened their faces to interest or mild negative facial affect, infants with higher 12-month cognitive performance were less likely to show negative vocal affect. We suggest that infant ability to modulate negative affect, and maternal ability to sustain positive affect, may be mutually reinforcing, together creating a dyadic climate that is associated with more optimal infant cognitive development.

Factors associated with permanent hearing impairment in infants treated with therapeutic hypothermia.

OBJECTIVE: To define the incidence of hearing impairment, document plasma gentamicin concentrations, and identify factors associated with permanent hearing impairment in infants subjected to therapeutic hypothermia for moderate or severe neonatal encephalopathy. STUDY DESIGN: Data were collected prospectively in a regional center providing therapeutic hypothermia. Cooled infants at ≥ 36 weeks gestation with moderate or severe neonatal encephalopathy were analyzed if a full dataset was available (n = 108), including clinical variables and gentamicin trough levels. Infants with hearing impairment were identified, and survivors were followed up with neurodevelopmental evaluation at age 18 months. Stepwise logistic regression identified factors associated with hearing impairment. RESULTS: Nine infants died, and among the survivors, 10.1% developed a permanent hearing impairment. The trough gentamicin level was above the recommended cutoff of 2 mg/L in 37% of the infants in the entire cohort and in 90% of the infants with hearing impairment. Logistic regression analysis identified high trough gentamicin level, low cord pH, and hypoglycemia (<46.8 mg/dL) in the first postnatal hour as significantly associated with hearing impairment. The need for inotropic support was close to significant (P = .055). CONCLUSION: Hearing impairment was a common finding among cooled infants. Plasma gentamicin levels were commonly >2 mg/L. Based on these findings, we propose changes in gentamicin dosing interval and trough level monitoring to minimize the risk of potentially toxic levels in cooled newborns.

Association between feeding difficulties and language delay in preterm infants using Bayley Scales of Infant Development-Third Edition.

OBJECTIVE: To evaluate the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-Third Edition at 18-22 months adjusted age among a cohort of extremely premature infants. STUDY DESIGN: This is a descriptive analysis of 1477 preterm infants born ≤ 26 weeks gestation or enrolled in a clinical trial between January 1, 2006 and March 18, 2008 at a National Institute of Child Health and Human Development Neonatal Research Network center who completed the 18-month neurodevelopmental follow-up assessment. At 18-22 months adjusted age, a comprehensive neurodevelopmental evaluation was performed by certified examiners including the Receptive and Expressive Language Subscales of the Bayley Scales of Infant Development-Third Edition and a standardized adjusted age feeding behaviors and nutritional intake. Data were analyzed using bivariate and multilevel linear and logistic regression modeling. RESULTS: Abnormal feeding behaviors were reported in 193 (13%) of these infants at 18-22 months adjusted age. Abnormal feeding patterns, days of mechanical ventilation, hearing impairment, and Gross Motor Functional Classification System level ≥ 2 each independently predicted lower composite language scores. CONCLUSIONS: At 18 months adjusted age, premature infants with a history of feeding difficulties are more likely to have language delay. Neuromotor impairment and days of mechanical ventilation are both important risk factors associated with these outcomes.

Neurodevelopmental outcome of extremely low birth weight infants with Candida infection.

OBJECTIVE: Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. STUDY DESIGN: ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. RESULTS: Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). CONCLUSIONS: In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

Predictive Value of the Münchener Funktionelle Entwicklungsdiagnostik Used to Determine Risk Factors for Motor Development in German Preterm Infants.

Early diagnosis of developmental delays is essential to providing early developmental care. The Münchener Funktionelle Entwicklungsdiagnostik (MFED) is a simple and cost-effective tool for diagnosing the development of infants and young children. Nevertheless, the MFED has not been a well-studied part of current research. This retrospective cohort study aims to detect risk factors and assess the impact of developmental care during the first twelve months of life, using the MFED. Furthermore, it determines the MFED's predictive value by comparing results with an international gold standard, the Bayley Scales of Infant Development II (BSID II). The study included 303 infants born between 2008-2013 in Rostock, Germany, with a birth weight of ≤1500 g and/or a gestational age of ≤32 weeks, who were evaluated with the MFED at twelve months of age. To ascertain the predictive value, 213 infants underwent BSID II assessment at 24 months of age. Intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and periventricular leukomalacia (PVL) were significantly associated with a higher risk of developmental delay across various domains. Post-discharge developmental care therapies did not indicate any clear beneficial effect on the infant's development. Nevertheless, some domains of MFED demonstrate predictive value, warranting increased attention for this diagnostic.

Influence of pre-eclampsia on 2-year neurodevelopmental outcome of very-low-birth-weight infants.

OBJECTIVE: To evaluate the influence of maternal pre-eclampsia on neurodevelopmental outcome in very-low-birth-weight (VLBW) infants at 6, 12, and 24 months of corrected age. METHODS: We conducted a retrospective cohort study of singleton VLBW infants between 2011 and 2018. The participants were divided into three groups: (1) mothers without pre-eclampsia, (2) pre-eclampsia without severe features, and (3) pre-eclampsia with severe features. The Bayley Scales of Infant Development third edition (BSID-III) was used to assess the neurodevelopment of participants. A BSID-III score < 85 was defined as neurodevelopmental impairment (NDI). RESULTS: Overall, 482 VLBW infants born to 482 mothers were enrolled, of whom 327 mothers did not have pre-eclampsia and 155 mothers had pre-eclampsia (58 without and 97 with severe features). The infants born to mothers with pre-eclampsia with severe features had the lowest BSID-III scores at 6, 12, and 24 months. After adjustments, maternal pre-eclampsia with severe features was significantly associated with cognitive NDI in their infants (adjusted odds ratio [aOR] 4.14) and language NDI (aOR 3.37) at 2 years of corrected age. CONCLUSIONS: VLBW fetuses born to mothers with pre-eclampsia with severe features have poorer 2-year neurodevelopmental outcome, which mainly manifests in the cognitive and language domains.