Neonatal Brain Response to Deviant Auditory Stimuli and Relation to Maternal Trait Anxiety.

OBJECTIVE: Excessive response to unexpected or "deviant" stimuli during infancy and early childhood represents an early risk marker for anxiety disorders. However, research has yet to delineate the specific brain regions underlying the neonatal response to deviant stimuli near birth and the relation to risk for anxiety disorders. The authors used task-based functional MRI (fMRI) to delineate the neonatal response to deviant stimuli and its relationship to maternal trait anxiety. METHODS: The authors used fMRI to measure brain activity evoked by deviant auditory stimuli in 45 sleeping neonates (mean age, 27.8 days; 60% female; 64% African American). In 41 of the infants, neural response to deviant stimuli was examined in relation to maternal trait anxiety on the State-Trait Anxiety Inventory, a familial risk factor for offspring anxiety. RESULTS: Neonates manifested a robust and widespread neural response to deviant stimuli that resembles patterns found previously in adults. Higher maternal trait anxiety was related to higher responses within multiple brain regions, including the left and right anterior insula, the ventrolateral prefrontal cortex, and multiple areas within the anterior cingulate cortex. These areas overlap with brain regions previously linked to anxiety disorders and other psychiatric illnesses in adults. CONCLUSIONS: The neural architecture sensitive to deviant stimuli robustly functions in newborns. Excessive responsiveness of some circuitry components at birth may signal risk for anxiety and other psychiatric disorders.

Cortical Processing of Multimodal Sensory Learning in Human Neonates.

Following birth, infants must immediately process and rapidly adapt to the array of unknown sensory experiences associated with their new ex-utero environment. However, although it is known that unimodal stimuli induce activity in the corresponding primary sensory cortices of the newborn brain, it is unclear how multimodal stimuli are processed and integrated across modalities. The latter is essential for learning and understanding environmental contingencies through encoding relationships between sensory experiences; and ultimately likely subserves development of life-long skills such as speech and language. Here, for the first time, we map the intracerebral processing which underlies auditory-sensorimotor classical conditioning in a group of 13 neonates (median gestational age at birth: 38 weeks + 4 days, range: 32 weeks + 2 days to 41 weeks + 6 days; median postmenstrual age at scan: 40 weeks + 5 days, range: 38 weeks + 3 days to 42 weeks + 1 days) with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI) and magnetic resonance (MR) compatible robotics. We demonstrate that classical conditioning can induce crossmodal changes within putative unimodal sensory cortex even in the absence of its archetypal substrate. Our results also suggest that multimodal learning is associated with network wide activity within the conditioned neural system. These findings suggest that in early life, external multimodal sensory stimulation and integration shapes activity in the developing cortex and may influence its associated functional network architecture.

Human neonates prefer colostrum to mature milk: Evidence for an olfactory bias toward the "initial milk"?

OBJECTIVES: Colostrum is the initial milk secretion which ingestion by neonates warrants their adaptive start in life. Colostrum is accordingly expected to be attractive to newborns. The present study aims to assess whether colostrum is olfactorily attractive for 2-day-old newborns when presented against mature milk or a control. METHODS: The head-orientation of waking newborns was videotaped in three experiments pairing the odors of: (a) colostrum (sampled on postpartum day 2, not from own mother) and mature milk (sampled on average on postpartum day 32, not from own mother) (n tested newborns = 15); (b) Colostrum and control (water; n = 9); and (c) Mature milk and control (n = 13). RESULTS: When facing the odors of colostrum and mature milk, the infants turned their nose significantly longer toward former (32.8 vs 17.7% of a 120-s test). When exposed to colostrum against the control, they responded in favor of colostrum (32.9 vs 16.6%). Finally, when the odor of mature milk was presented against the control, their response appeared undifferentiated (26.7 vs 28.6%). CONCLUSIONS: These results indicate that human newborns can olfactorily differentiate conspecific lacteal fluids sampled at different lactation stages. They prefer the odor of the mammary secretion - colostrum - collected at the lactation stage that best matches the postpartum age of their own mother. These results are discussed in the context of the earliest mother-infant chemo-communication. Coinciding maternal emission and offspring reception of chemosignals conveyed in colostrum may be part of the sensory precursors of attunement between mothers and infants.

Effect of a Short-Time Probiotic Supplementation on the Abundance of the Main Constituents of the Gut Microbiota of Term Newborns Delivered by Cesarean Section-A Randomized, Prospective, Controlled Clinical Trial.

The gut microbiota plays a pivotal role in the maintenance of human health. Numerous factors, including the mode of delivery, impact early gut colonization in newborns. Recent research focuses on the use of probiotics in the prevention of gut dysbiosis in newborns delivered by cesarean section (CS). The objective of this study was to determine whether a probiotic supplement given to newborns delivered by CS during their stay in the maternity ward alters the pattern of early gut colonization by lactic acid bacteria versus potential pathogens. A prospective, randomized trial was conducted. In total, 150 newborns, born at 38-40 weeks gestational age and delivered by CS, were included in the study. They were randomized into the intervention group, supplemented orally with a probiotic containing Bifidobacterium breve PB04 and Lactobacillus rhamnosus KL53A, and the control group. Stool samples were obtained on days 5 and 6 of life and after one month of life and were analyzed for the presence and abundance of the main groups of bacteria. An application of two probiotic bacteria during the first days of life after CS resulted in quick and abundant colonization by days 5 and 6, with high populations of L. rhamnosus and B. breve. The applied bacterial strains were present in the majority of neonates one month after. The supplementation of term neonates delivered by cesarean section immediately after birth with a mixture of L. rhamnosus and B. breve enriched the gut microbiota composition with lactic acid bacteria.

Neonatal Iron: Factors Influencing its Level and Associated Complications - a Review Article.

BACKGROUND: Iron is an essential micronutrient which plays a significant role, particularly vital for early brain growth and function. Maternal iron condition influences the iron status of neonates since iron transferred from the mother is the only source for fetal iron. A depletion in iron as a result of rapid growth leads to iron deficiency which is common in neonates. Although there are inconsistencies with regard to the normal reference ranges for neonatal iron level, the current review summarized literature to provide compressive information about neonatal iron status and factors that influence its level. METHODS: This is a narrative review on the basis of relevant literatures mainly on neonatal iron from peer-reviewed journals. Electronic databases such as PubMed, PMC, Scopus, Science Direct, Google scholar, Google, and Yahoo were used to retrieve relevant literatures using key terms like "newborn iron, neonatal iron, iron overload, maternal factors, complication, iron level and neonates" separately and in combination. RESULTS: Several factors had been postulated as factors associated with neonatal iron status. The current review figured out that maternal obesity, gestational diabetes mellitus, preterm delivery, placental transferrin receptor, inappropriate iron supplementation, use of iron fortified formula, uses of recombinant erythropoietin therapy, smoking, maternal iron deficiency anemia, umbilical cord clamping, and transfusion are the major factors which can influence neonatal iron level. These factors may have either positive or negative effects on neonatal iron level. Both iron deficiency and iron overload at some stage in the fetal development or at early stage of neonatal development cause abnormal functions of multiple organ system of neonates and subsequently contributed to neonatal and childhood morbidity and mortality. CONCLUSIONS: By one and other means insufficient, late and extra maternal iron supplementation, early and delayed umbilical cord clamping have negative effects on the iron level of neonates. Therefore, careful prenatal and antenatal follow-up need to be strengthened with due emphasis for maternal iron assessment.

The frequency-following response (FFR) to speech stimuli: A normative dataset in healthy newborns.

The Frequency-Following Response (FFR) is a neurophonic auditory evoked potential that reflects the efficient encoding of speech sounds and is disrupted in a range of speech and language disorders. This raises the possibility to use it as a potential biomarker for literacy impairment. However, reference values for comparison with the normal population are not yet established. The present study pursues the collection of a normative database depicting the standard variability of the newborn FFR. FFRs were recorded to /da/ and /ga/ syllables in 46 neonates born at term. Seven parameters were retrieved in the time and frequency domains, and analyzed for normality and differences between stimuli. A comprehensive normative database of the newborn FFR is offered, with most parameters showing normal distributions and similar robust responses for /da/ and /ga/ stimuli. This is the first normative database of the FFR to characterize normal speech sound processing during the immediate postnatal days, and corroborates the possibility to record the FFRs in neonates at the maternity hospital room. This normative database constitutes the first step towards the detection of early FFR abnormalities in newborns that would announce later language impairment, allowing early preventive measures from the first days of life.

Physiological and emotional effects of pentatonic live music played for preterm neonates and their mothers in the Newborn Intensive Care Unit: A randomized controlled trial.

OBJECTIVE: Despite attempts to increase calmness in the Newborn Intensive Care Unit (NICU), preterm neonates still experience stress. The question arises how to further promote the infants' wellbeing. Therefore, the immediate effects of pentatonic live music on preterm infants and their mothers were examined. DESIGN AND METHODS: In a two-centre randomized controlled trial with crossover design preterm infants were exposed sequentially to two conditions: live pentatonic harp music (LPHM) used in Anthroposophic Medicine or standard care. The order of the conditions was randomized within each subject. The primary outcome was change of the number of oxygen desaturations < 90%/h, whereas secondary outcomes were: heart rate, respiratory rate, oxygen saturation, heart rate variability (HRV), the perfusion index, pulse-transit-time and maternal anxiety and others not reported on in this article. RESULTS: 21 preterm infants were randomized (14 girls), mean gestational age at measurement 35 + 0 weeks (SD 1 week). The primary outcome parameter showed no significant changes. Regarding the secondary outcomes the comparison of the pre-post-differences between the conditions showed significant effects for the HRV parameters pNN50 (ΔpNN50 = 1.46%, z = -2.47, p = .001) and SDNN (ΔSDNN=-0.06 ms, z = -2.25, p = .002). The music intervention significantly increased the values of pNN50 (Mdn 1.2% vs. 2.6%, p = 0.04) and marginally those of SDNN (Mdn 31.7 ms vs. 36.4 ms, p = 0.05). No changes were found in the other parameters. CONCLUSIONS: While the use of music in the NICU had no effect on the number of oxygen desaturations, it increased two HRV parameters indicative of infants' parasympathetic tone.

[Effect of docosahexenoic acid supplementation on infant's growth and body mass index during maternal pregnancy].

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.

Effect of docosahexenoic acid supplementation on infant's growth and body mass index during maternal pregnancy / 中华流行病学杂志

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.

The road to life. Neonatal transitions to extra-uterine life.

The onset of labour and birth initiates profound changes for infants. It is essential to understand these unique aspects of childbirth; doing so will equip midwives with the ability to detect deviations from expected trajectories, take appropriate actions, but most importantly support normal birth transitions. These transitions involve a complex cascade of physiological, anatomical and behavioural changes acting in concert. This article overviews essential knowledge about the early adaptive changes after birth and considers initial cardio-respiratory and metabolic responses to birth, together with how midwives can support the best possible start for infants.

What can you do to protect the newborn brain?

PURPOSE OF REVIEW: Hypoxic-ischemic brain injury is a leading cause of mortality and morbidity in neonates. Treating such injury by interrupting the excitotoxic-oxidative cascade is of immense importance. This review will focus on novel techniques of neuroprotection and describe the latest advances in established therapeutic methods. KEY FINDINGS: Although the primacy of therapeutic hypothermia in treating hypoxic-ischemic encephalopathy is well established, recent research establishes that the arbitrarily chosen regimen of cooling to 33°C for 72 h may indeed be the most appropriate method. The optimal duration of antenatal magnesium therapy for neuroprotection remains unsettled, though it is reassuring that even 12 h or less of magnesium therapy results in comparable neurological outcomes. Combining adjuvant therapies such as melatonin or erythropoietin with therapeutic hypothermia results in favorable neurological outcomes compared with hypothermia alone. Finally, stem cell-based therapies show considerable potential in preclinical studies. SUMMARY: Significant advances have occurred in the management of neonatal brain injury. With establishment of the optimal temperature and duration of hypothermia, combinatory therapies using adjuncts hold the greatest promise. Promising preclinical approaches such as stem cell-based therapy and use of noble gases need to be confirmed with clinical trials.

Magnetoencephalographic signatures of numerosity discrimination in fetuses and neonates.

Numerosity discrimination has been demonstrated in newborns, but not in fetuses. Fetal magnetoencephalography allows non-invasive investigation of neural responses in neonates and fetuses. During an oddball paradigm with auditory sequences differing in numerosity, evoked responses were recorded and mismatch responses were quantified as an indicator for auditory discrimination. Thirty pregnant women with healthy fetuses (last trimester) and 30 healthy term neonates participated. Fourteen adults were included as a control group. Based on measurements eligible for analysis, all adults, all neonates, and 74% of fetuses showed numerical mismatch responses. Numerosity discrimination appears to exist in the last trimester of pregnancy.

Body temperature changes of newborns under fluorescent versus LED phototherapy.

OBJECTIVE: To determine changes in body temperature (BT) of hyperbilirubinemic newborns under conventional phototherapy with fluorescent lamps and light emitting diodes (LED) at different irradiances. METHODS: Otherwise healthy newborn infants >34 wk gestational age (GA) hospitalized for indirect hyperbilirubinemia, requiring phototherapy in the first 10 d of life were enrolled. Infants who received conventional phototherapy with fluorescent lamps (10-15 µW/cm(2)/nm irradiance) were defined as group 1, LED phototherapy of 26-60 µW/cm(2)/nm irradiance as group 2, and LED phototherapy of 60-120 µW/cm(2)/nm irradiance as group 3. Primary outcome measure was mean BT which was defined as arithmetical mean of axillary BT measured at 2 h intervals during the first day of phototherapy. RESULTS: Thirty patients were enroled in each group. Mean birth weight and GA of the total cohort was 2800 ± 530 g and 36.6 ± 2 wk, respectively. Baseline demographic variables and serum total bilirubin levels were similar among groups. Mean BT was 36.7 ± 0.1 °C in group 1, 36.6 ± 0.2 °C in group 2, 37.7 ± 0.2 °C in group 3. Mean BT was higher in group 3 compared to group 1 (p < 0.001) and group 2 (p < 0.001). Group 1 and group 2 had similar mean BT measurements (p = 0.09). During phototherapy all the patients in group 3 had at least one BT measurement ≥ 37.5 °C and 77 % had BT ≥ 38 °C. Only one patient in group 2 had BT ≥ 37.5 °C which was also ≥ 38 °C. During phototherapy all BT measurements were <37.5 °C in group 1. CONCLUSIONS: LED phototherapy of ≥ 60 µW/cm(2)/nm intensity significantly increases BT in hyperbilirubinemic newborns.

Dissociation between small and large numerosities in newborn infants.

In the first year of life, infants possess two cognitive systems encoding numerical information: one for processing the numerosity of sets of 4 or more items, and the second for tracking up to 3 objects in parallel. While a previous study showed the former system to be already present a few hours after birth, it is unknown whether the latter system is functional at this age. Here, we adapt the auditory-visual matching paradigm that previously revealed sensitivity to large numerosities to test sensitivity to numerosities spanning the range from 2 to 12. Across studies, newborns discriminated pairs of large numerosities in a 3:1 ratio, even when the smaller numerosity was 3 (3 vs. 9). In contrast, newborn infants failed to discriminate pairs including the numerosity 2, even at the same ratio (2 vs. 6). These findings mirror the dissociation that has been reported with older infants, albeit with a discontinuity situated between numerosities 2 and 3. Two alternative explanations are compatible with our results: either newborn infants have a separate system for processing small sets, and the capacity of this system is limited to 2 objects; or newborn infants possess only one system to represent numerosities, and this system either is not functional or is extremely imprecise when it is applied to small numerosities.

Infants' brain responses for speech sound changes in fast multifeature MMN paradigm.

OBJECTIVE: We investigated whether newborn speech-sound discrimination can be studied in 40 min using fast multifeature mismatch negativity (MMN) paradigm and do the results differ from those obtained with the traditional oddball paradigm. METHODS: Newborns' MMN responses to five types of changes (consonant identity, F0, intensity, vowel duration and vowel identity) were recorded in the multifeature group (N=15) and vowel duration and vowel identity changes in the oddball group (N=13), after which the MMNs from both groups were compared with each others. RESULTS: Statistically significant MMNs in the 190-600 ms time range from the stimulus onset were found for most change types in both paradigms. Newborn MMN responses were predominantly positive but a small number of participants elicited negative MMNs instead. MMN amplitudes did not differ between the multifeature and oddball groups. CONCLUSIONS: Newborn speech-sound discrimination can be assessed in a short recording time using the fast multifeature paradigm. SIGNIFICANCE: The paradigm presented here can be used to record extensive auditory discrimination profiles in newborns and assess development of speech-sound discrimination and its difficulties.

Amniotic fluid elicits appetitive responses in human newborns: fatty acids and appetitive responses.

In humans, maternal cues guide newborns to the maternal breast, and transitional cues may be present in maternal-fetal fluids. The aim of the present study was to determine the consistent presence of sensorial cues in three maternal-fetal fluids--amniotic fluid, colostrum, and milk--and test the ability of these cues to produce appetitive responses in newborns. In the analytical study, gas chromatography-mass spectrometry (GC-MS) detected eight fatty acids consistently present in the amniotic fluid, colostrum, and milk from 12 healthy volunteers, but we do not find a mammalian pheromone, identified in another mammalian species (rabbits), in another 30 volunteers. In the behavioral study, we explored the ability of amniotic fluid or its fatty acids to produce appetitive responses in 19 human newborns <24 hr after birth. Exposure to swabs impregnated with amniotic fluid or an artificial fatty acid mixture produced a longer duration of facial reactions that suggested appetitive (sucking) movements compared with respective vehicles (i.e., propylene glycol or centrifuged amniotic fluid with a low fatty acid content verified by GC-MS). We conclude that the fatty acids contained in amniotic fluid may constitute a transitional sensorial cue that guides newborns to the maternal breast.

Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort study.

CONTEXT: Inconsistent associations between maternal vitamin D status and fetal size have been published in small studies. OBJECTIVE: Our objective was to examine the association between maternal 25-hydroxyvitamin D [25(OH)D] levels and measures of newborn and placental weight. DESIGN AND SETTING: We measured maternal 25(OH)D in mothers from the Collaborative Perinatal Project, an observational cohort conducted in 12 U.S. medical centers from 1959 to 1965. PARTICIPANTS: Women delivering singleton, term, live births with 25(OH)D measured at a gestation of 26 wk or less (n = 2146). MAIN OUTCOME MEASURES: Birth weight, ponderal index, placental weight, the placental to fetal weight ratio, and small for gestational age were measured. Hypotheses were formulated after data collection. RESULTS: After confounder adjustment, mothers with 25(OH)D of 37.5 nmol/liter or greater gave birth to newborns with 46 g [95% confidence interval (CI), 9-82 g] higher birth weights and 0.13 cm (0.01-0.25 cm) larger head circumferences compared with mothers with less than 37.5 nmol/liter. Birth weight and head circumference rose with increasing 25(OH)D up to 37.5 nmol/liter and then leveled off (P < 0.05). No association was observed between 25(OH)D and ponderal index, placental weight, or the placental to fetal weight ratio. Maternal 25(OH)D of 37.5 nmol/liter or greater vs. less than 37.5 nmol/liter in the first trimester was associated with half the risk of small for gestational age (adjusted odds ratio 0.5; 95% CI 0.3-0.9), but no second-trimester association was observed. CONCLUSIONS: Maternal vitamin D status is independently associated with markers of physiological and pathological growth in term infants. Adequately powered randomized controlled trials are needed to test whether maternal vitamin D supplementation may improve fetal growth.

Brainstem auditory response findings in term neonates in intensive care unit.

OBJECTIVES: Whether term infants in neonatal intensive care unit (NICU) have brainstem auditory abnormalities remains to be determined. This study aimed to detect any abnormality in brainstem auditory function in term neonates who are admitted to NICU. METHODS: From a NICU, we recruited 55 term neonates with various perinatal problems. They were studied during the first week after birth using brainstem auditory evoked response (BAER), and the results were compared with normal term controls. RESULTS: Wave I and III latencies and I-III interpeak interval of the evoked response in the NICU term neonates were similar to those in the controls. Wave V latency and I-V and III-V interpeak intervals tended to be increased at 21/s clicks. The increase was more obvious at higher rates 51 and 91/s. Analysis of variance revealed that at 21/s clicks only III-V interval was significantly increased (p < 0.05). At 51 and 91/s clicks, wave V latency and III-V and I-V intervals were significantly increased (p < 0.05-0.01). The rates of the abnormalities were seen more at higher than at lower click rates. The amplitudes of waves I, III, and V in the NICU neonates were all slightly reduced, but none differed significantly from the controls. CONCLUSIONS: There are some abnormalities in BAER in term neonates in NICU, suggesting functional abnormality in the auditory brainstem in NICU infants.