Navigating accent variability: 24-month-olds recognize known words spoken in an unfamiliar accent but require additional support to learn new words.

As infants learn their native languages, they must also learn to contend with variability across speakers of those languages. Here, we examine 24-month-olds' ability to process speech in an unfamiliar accent. We demonstrate that 24-month-olds successfully identify the referents of known words in unfamiliar-accented speech but cannot use known words alone to infer new word meanings. However, when the novel word occurs in a supportive referential context, with the target referent visually available, 24-month-olds successfully learn new word-referent mappings. Thus, 24-month-olds recognize and learn words in unfamiliar accents, but unfamiliar-accented speech may pose challenges for more sophisticated language processing strategies.

Nutrition for Infants with Congenital Heart Disease.

Perioperative malnutrition in infants with congenital heart disease can lead to significant postnatal growth failure and poor short- and long-term outcomes. A standardized approach to nutrition is needed for the neonatal congenital heart disease population, taking into consideration the type of cardiac lesion, the preoperative and postoperative period, and prematurity. Early enteral feeding is beneficial and should be paired with parenteral nutrition to meet the fluid and nutrient needs of the infant.

Dilemmas in parenteral glucose delivery and approach to glucose monitoring and interpretation in the neonate.

Glucose control continues to be challenging for intensivists, in particular in high-risk neonates. Many factors play a role in glucose regulation including intrinsic and extrinsic factors. Optimal targets for euglycemia are debatable with uncertain short and long-term effects. Glucose measurement technology has continued to advance over the past decade; unfortunately, the availability of these advanced devices outside of research continues to be problematic. Treatment approaches should be individualized depending on etiology, symptoms, and neonatal conditions. Glucose infusions should be titrated based upon variations in organ glucose uptake, co-morbidities and postnatal development. In this article we summarize the most common dilemmas encountered in the NICU: ranges for euglycemia, physiological differences, approach for glucose measurements, monitoring and best strategies to control parenteral glucose delivery.

Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates.

Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms.

A Randomized Trial of an Exclusive Human Milk Diet in Neonates with Single Ventricle Physiology.

OBJECTIVE: To determine whether weight gain velocity (g/kg/day) 30 days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet. STUDY DESIGN: In this multicenter, randomized, single blinded, controlled trial, term neonates 7 days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed. RESULTS: We enrolled 107 neonates (exclusive human milk = 55, control = 52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12 g/day [IQR, 5-18 g/day] vs 8 g/day [IQR, 0.4-14 g/day], respectively; P = .03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P = .04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups. CONCLUSIONS: Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (www. CLINICALTRIALS: gov, Trial ID: NCT02860702).

Effects of human milk on body composition and growth in very low birthweight infants.

OBJECTIVE: To compare body composition and growth in very low birthweight infants according to their source of human milk: maternal expressed breast milk (MEBM) versus donor breast milk (DBM). We hypothesized that infants fed predominately MEBM would exhibit reduced body fat percentage compared to those fed predominately DBM. METHODS: Premature infants weighing ≤1500 g on an exclusive human milk diet were enrolled in a single-center study between 2017 and 2021. Demographic data and anthropometric measurements were collected. All infants underwent body composition analysis via dual energy x-ray absorptiometry at 36 weeks corrected post menstrual age. RESULTS: A total of 60 infants were enrolled and 48 were included in the primary analysis. No differences were detected in percent body fat (14 vs. 12%, p = 0.7) or fat-free mass (2050 vs. 2130 g, p = 0.7). Both groups displayed similar growth and anthropometric measurements. Caloric and macronutrient intake between groups was similar. CONCLUSION: In the cohort of patients studied, no differences were observed in percent body fat based on primary human milk type intake in the first 28 postnatal days. Further investigation is required in a larger population of exclusive human milk fed preterm infants to determine if body composition differences exist based on an infant's primary human milk source. IMPACT: Premature infants are at risk for altered body composition at term corrected age, specifically increased body fat percentage, which may have implications for the future. To our knowledge this is the first study exploring body composition outcomes based on an infant's primary human milk source. Infants fed exclusive human milk (e.g., donor vs. maternal) displayed similar percent body fat and growth outcomes.

Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis.

Preterm birth is the leading cause of death in children under 5 years of age. Premature infants who receive life-saving oxygen therapy often develop bronchopulmonary dysplasia (BPD), a chronic lung disease. Infants with BPD are at a high risk of abnormal neurodevelopment, including motor and cognitive difficulties. While neural progenitor cells (NPCs) are crucial for proper brain development, it is unclear whether they play a role in BPD-associated neurodevelopmental deficits. Here, we show that hyperoxia-induced experimental BPD in newborn mice led to lifelong impairments in cerebrovascular structure and function as well as impairments in NPC self-renewal and neurogenesis. A neurosphere assay utilizing nonhuman primate preterm baboon NPCs confirmed impairment in NPC function. Moreover, gene expression profiling revealed that genes involved in cell proliferation, angiogenesis, vascular autoregulation, neuronal formation, and neurotransmission were dysregulated following neonatal hyperoxia. These impairments were associated with motor and cognitive decline in aging hyperoxia-exposed mice, reminiscent of deficits observed in patients with BPD. Together, our findings establish a relationship between BPD and abnormal neurodevelopmental outcomes and identify molecular and cellular players of neonatal brain injury that persist throughout adulthood that may be targeted for early intervention to aid this vulnerable patient population.

Neurodevelopmental outcomes of extremely preterm infants fed an exclusive human milk-based diet versus a mixed human milk + bovine milk-based diet: a multi-center study.

OBJECTIVE: The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18-22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV). STUDY DESIGN: Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18-22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis. RESULTS: 252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32). CONCLUSION: In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18-22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes.

Neonatal Glucose Homeostasis.

Hypoglycemia is a common condition in the newborn period. Several intrinsic and extrinsic factors play a role in the degree/duration of hypoglycemia. Multiple thresholds have been proposed as a potential point whereby hypoglycemia may have short and long-term adverse effects. Rather than a "numerical" threshold, treatment approaches should be individualized and tailored to the etiology, symptoms, and neonatal underlying conditions. Hyperglycemia in the newborn period is commonly seen in preterm infants and can exert gluco-toxic effects in organs at critical periods of development. Considering the peripheral insulin resistance (IR) of prematurity and contributing factors is key to achieving euglycemia.

Endothelial Adenosine Monophosphate-Activated Protein Kinase-Alpha1 Deficiency Potentiates Hyperoxia-Induced Experimental Bronchopulmonary Dysplasia and Pulmonary Hypertension.

Bronchopulmonary dysplasia and pulmonary hypertension, or BPD-PH, are serious chronic lung disorders of prematurity, without curative therapies. Hyperoxia, a known causative factor of BPD-PH, activates adenosine monophosphate-activated protein kinase (AMPK) α1 in neonatal murine lungs; however, whether this phenomenon potentiates or mitigates lung injury is unclear. Thus, we hypothesized that (1) endothelial AMPKα1 is necessary to protect neonatal mice against hyperoxia-induced BPD-PH, and (2) AMPKα1 knockdown decreases angiogenesis in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs). We performed lung morphometric and echocardiographic studies on postnatal day (P) 28 on endothelial AMPKα1-sufficient and -deficient mice exposed to 21% O2 (normoxia) or 70% O2 (hyperoxia) from P1-P14. We also performed tubule formation assays on control- or AMPKα1-siRNA transfected HPMECs, exposed to 21% O2 or 70% O2 for 48 h. Hyperoxia-mediated alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and PH were significantly amplified in endothelial AMPKα1-deficient mice. AMPKα1 siRNA knocked down AMPKα1 expression in HPMECs, and decreased their ability to form tubules in normoxia and hyperoxia. Furthermore, AMPKα1 knockdown decreased proliferating cell nuclear antigen expression in hyperoxic conditions. Our results indicate that AMPKα1 is required to reduce hyperoxia-induced BPD-PH burden in neonatal mice, and promotes angiogenesis in HPMECs to limit lung injury.

Structural Refinement of the Auditory Brainstem Neurons in Baboons During Perinatal Development.

Children born prematurely suffer from learning disabilities and exhibit reading, speech, and cognitive difficulties, which are associated with an auditory processing disorder. However, it is unknown whether gestational age at delivery and the unnatural auditory environment in neonatal intensive care units (NICU) collectively affect proper auditory development and neuronal circuitry in premature newborns. We morphologically characterized fetal development of the medial superior olivary nucleus (MSO), an area important for binaural hearing and sound localization, in the auditory brainstem of baboon neonates at different gestational ages. Axonal and synaptic structures and the tonotopic differentiation of ion channels in the MSO underwent profound refinements after hearing onset in the uterus. These developmental refinements of the MSO were significantly altered in preterm baboon neonates in the NICU. Thus, the maternal environment in uterus is critical for auditory nervous system development during the last trimester of pregnancy and critically affects the anatomic and functional formation of synapses and neural circuitry in the preterm newborn brain.

Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp.

Parenteral Nutrition (PN) Associated Liver Disease (PNALD) affects up to 60% of neonates; however, techniques for diagnosing and monitoring disease progression remain limited. The neonatal baboon model may provide a unique opportunity to identify serologic markers associated with this disease. The purpose of this study was to investigate if Hyaluronic Acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP1), Amino-terminal Propeptide of Type-III Collagen (PIIINP) and Enhanced Liver Fibrosis (ELF) score associate with histological liver disease in neonatal baboons exposed to PN. Preterm baboons delivered via c-section at 67% gestation received PN for 14 days with or without Intralipid (PRT+IL, PRT-IL, respectively) or were sacrificed after birth (PRTCTR). Term baboons were sacrificed after birth (TERMCTR) or survived 14 days (TERM+14d). Serum HA, TIMP1, and PIIINP concentrations were measured by ELISA. A blinded pathologist assigned liver histological scores following necropsy. HA increased 9.1-fold, TIMP1 increased 2.2-fold, and ELF score increased 1.4-fold in PRT-IL compared to PRTCTR. ALT, AST, and GGT were within normal limits and did not vary between groups. A trend towards increased fibrosis was found in PRT-IL baboons. Microvesicular hepatocyte steatosis and Kupffer cell hypertrophy were elevated in PRT-IL vs PRTCTR. HA and TIMP1 were significantly elevated in preterm baboons with early histological findings of liver disease evidenced by hepatic steatosis, Kupffer cell hypertrophy and a trend towards fibrosis whereas traditional markers of liver disease remained normal. These novel markers could potentially be utilized for monitoring early hepatic injury in neonates.

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population.

BACKGROUND: Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. METHODS: Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. RESULTS: Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22. CONCLUSIONS: The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.

Microvillus inclusion disease, a diagnosis to consider when abnormal stools and neurological impairments run together due to a rare syntaxin 3 gene mutation.

BACKGROUND: Microvillus Inclusion Disease (MVID) was first described in the literature in 1978 with presentation of severe watery diarrhea, failure to thrive, and metabolic acidosis. Mutations in the myosin Vb (MYO5B) gene have been identified as causative for MVID, but other clinical manifestations and associations with novel mutations are lacking. METHODS: We report a full-term infant admitted to the neonatal intensive care unit (NICU) with abdominal distension and inability to sustain full enteral feeds. A retrospective chart review and review of the literature was performed. RESULTS: An infant with abnormal, mucoid-like stringy stools was incidentally found to have severe metabolic acidosis on routine lab monitoring. Acidosis corrected with total parenteral nutrition (TPN), but the infant experienced recurrent episodes of acidosis with enteral feeds. He was also noted to have abnormal ocular movements, fluctuating tonicity, and staring spells. He underwent an extensive workup and the diagnosis of microvillus inclusion disease was made by findings on electron microscopy. The diagnosis was confirmed with whole exome sequencing, showing a rare homozygous mutation in the syntaxin 3 (STX3) gene. This is the fifth reported patient with microvillus inclusion disease with a mutation in this gene, and the first with abnormal neurologic findings. CONCLUSION: It is important to consider MVID in the differential diagnosis of a neonate or infant with abnormal stools, metabolic acidosis, with and without neurologic symptoms for prompt referral and treatment.

High Branched-Chain Amino Acid Concentrations Are Found in Preterm Baboons Receiving Intravenous Amino Acid Solutions and Mimic Alterations Found in Preterm Infants.

BACKGROUND: Parenteral amino acid (AA) nutrition administration after premature birth is necessary to ensure adequate growth and neurodevelopment. However, optimizing safety and efficacy remains a major challenge. This study investigated the effects of intravenous AA administration on plasma AA profiles in premature baboons and infants. METHODS: Premature baboons were delivered by cesarean section at 125 days (67% gestation) and chronically ventilated. At 24 hours of life, a parenteral AA protocol comparable to the early and high AA regimens used in premature infants was initiated. Serial plasma AA concentrations were obtained on days of life (DOLs) 1, 3, and 7 and compared with concentrations at similar DOLs from preterm infants. Fetal baboon (165 ± 2 days; 89% gestation) and term baboon plasma AA concentrations were obtained for comparison. RESULTS: Premature baboons receiving early and high parenteral AA supplementation exhibited significant differences in plasma AA concentrations compared with fetuses. In particular, concentrations of leucine, isoleucine, valine, and ornithine were elevated (fold increase: 2.14, 2.03, 1.95, and 16.5, respectively; P < 0.001) on DOL 3 vs fetuses. These alterations mimicked those found in preterm infants. CONCLUSION: Early and high AA supplementation in extremely premature baboons significantly disrupted plasma AA concentrations. Elevated concentrations of branched-chain AAs and ornithine raise concerns for adverse neurodevelopmental outcomes. These results are consistent with those found in premature human infants and emphasize the need to optimize parenteral AA solutions for the unique metabolic requirements of premature infants. Improved technologies for rapid monitoring of AA concentrations during treatment are essential.

Effects of intravenous AICAR (5-aminoimidazole-4-carboximide riboside) administration on insulin signaling and resistance in premature baboons, Papio sp.

Premature baboons exhibit peripheral insulin resistance and impaired insulin signaling. 5' AMP-activated protein kinase (AMPK) activation improves insulin sensitivity by enhancing glucose uptake (via increased glucose transporter type 4 [GLUT4] translocation and activation of the extracellular signal-regulated kinase [ERK]/ atypical protein kinase C [aPKC] pathway), and increasing fatty acid oxidation (via inhibition of acetyl-CoA carboxylase 1 [ACC]), while downregulating gluconeogenesis (via induction of small heterodimer partner [SHP] and subsequent downregulation of the gluconeogenic enzymes: phosphoenolpyruvate carboxykinase [PEPCK], glucose 6-phosphatase [G6PASE], fructose- 1,6-bisphosphatase 1 [FBP1], and forkhead box protein 1 [FOXO1]). The purpose of this study was to investigate whether pharmacologic activation of AMPK with AICAR (5-aminoimidazole-4-carboximide riboside) administration improves peripheral insulin sensitivity in preterm baboons. 11 baboons were delivered prematurely at 125±2 days (67%) gestation. 5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1. 6 animals were in the placebo group. Euglycemic hyperinsulinemic clamps were performed at 5±2 and 14±2 days of life. Key molecules potentially altered by AICAR (AMPK, GLUT4, ACC, PEPCK, G6PASE, FBP1, and FOXO1), and the insulin signaling molecules: insulin receptor (INSR), insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were measured using RT-PCR and western blotting. AICAR infusion did not improve whole body insulin-stimulated glucose disposal in preterm baboons (12.8±2.4 vs 12.4±2.0 mg/(kg·min), p = 0.8, placebo vs AICAR). One animal developed complications during treatment. In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α). In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion. This study provides evidence that AICAR does not improve insulin sensitivity in premature euglycemic baboons, and may have adverse effects.

Prematurity disrupts glomeruli development, whereas prematurity and hyperglycemia lead to altered nephron maturation and increased oxidative stress in newborn baboons.

BackgroundPremature birth occurs when nephrogenesis is incomplete and has been linked to increased renal pathologies in the adult. Metabolic factors complicating preterm birth may have additional consequences for kidney development. Here, we evaluated the effects of prematurity and hyperglycemia on nephrogenesis in premature baboons when compared with those in term animals.MethodsBaboons were delivered prematurely (67% gestation; n=9) or at term (n=7) and survived for 2-4 weeks. Preterm animals were classified by glucose control during the first 5 days of life: normoglycemic (PtN; serum glucose 50-100 mg/dl, n=6) and hyperglycemic (PtH; serum glucose 150-250 mg/dl, n=3). Kidneys were assessed histologically for glomeruli relative area, maturity, size, and overall morphology. Kidney lysates were evaluated for oxidative damage with 4-hydroxynonenal (4-HNE) antibody.ResultsHistological examination revealed decreased glomeruli relative area (P<0.05), fewer glomerular generations (P<0.01), and increased renal corpuscle area (P<0.001) in preterm compared with those in term animals. Numbers of apoptotic glomeruli were similar between groups. PtH kidneys exhibited reduced nephrogenic zone width (P<0.0001), increased numbers of mature glomeruli (P<0.05), and increased 4-HNE staining compared with those in PtN kidneys.ConclusionPrematurity interrupts normal kidney development, independent of glomerular cell apoptosis. When prematurity is complicated by hyperglycemia; kidney development shifts toward accelerated maturation and increased oxidative stress.

Favorable Outcomes of Preterm Infants With Parenteral Nutrition-associated Liver Disease Treated With Intravenous Fish Oil-based Lipid Emulsion.

OBJECTIVES: The aim of the study was to determine the acute and long-term outcomes of preterm infants treated with an intravenous fish oil-based lipid emulsion (FishLE) for parenteral nutrition-associated liver disease (PNALD). METHODS: Preterm infants 14 days to 24 months of age with anatomic short gut or severe intestinal dysmotility, serum direct bilirubin ≥4 mg/dL, and requiring >60% calories from parenteral nutrition were eligible. Enrolled infants received 1 g ·â€Škg ·â€Šday of FishLE until resolution of direct hyperbilirubinemia or return of enteral nutrition. Acute clinical effects and biochemical markers of liver function were monitored. Growth and developmental scores at 6 and 12 months postmenstrual age (PMA) were assessed and compared with controls matched by gestational age (GA). RESULTS: Thirteen patients with mean GA of 28 ±â€Š4 weeks were treated and compared with 119 GA-matched controls. Their mean direct bilirubin was 9.8 ±â€Š6.4 mg/dL at enrollment. All infants had resolution of cholestasis after study completion. There were no acute adverse events, deaths, or liver/intestinal transplants. Weight and head circumference were similar between FishLE-treated patients and controls at 6- and 12-month PMA. Cognitive and motor scores were decreased at 6 and 12 months PMA in FishLE-treated infants. Logistic regression analysis showed that prolonged hospitalization was detrimental to cognitive and motor development, whereas treatment was not. CONCLUSIONS: The use of intravenous FishLEs in premature infants appears to be safe and reverses PNALD despite significant liver disease and intestinal failure. This therapy should be used in preterm infants with PNALD and followed long term to evaluate development.

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-ß, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity.

Differences in the Association between Segment and Language: Early Bilinguals Pattern with Monolinguals and Are Less Accurate than Late Bilinguals.

Early bilinguals often show as much sensitivity to L2-specific contrasts as monolingual speakers of the L2, but most work on cross-language speech perception has focused on isolated segments, and typically only on neighboring vowels or stop contrasts. In tasks that include sounds in context, listeners' success is more variable, so segment discrimination in isolation may not adequately represent the phonetic detail in stored representations. The current study explores the relationship between language experience and sensitivity to segmental cues in context by comparing the categorization patterns of monolingual English listeners and early and late Spanish-English bilinguals. Participants categorized nonce words containing different classes of English- and Spanish-specific sounds as being more English-like or more Spanish-like; target segments included phonemic cues, cues for which there is no analogous sound in the other language, or phonetic cues, cues for which English and Spanish share the category but for which each language varies in its phonetic implementation. Listeners' language categorization accuracy and reaction times were analyzed. Our results reveal a largely uniform categorization pattern across listener groups: Spanish cues were categorized more accurately than English cues, and phonemic cues were easier for listeners to categorize than phonetic cues. There were no differences in the sensitivity of monolinguals and early bilinguals to language-specific cues, suggesting that the early bilinguals' exposure to Spanish did not fundamentally change their representations of English phonology. However, neither did the early bilinguals show more sensitivity than the monolinguals to Spanish sounds. The late bilinguals however, were significantly more accurate than either of the other groups. These findings indicate that listeners with varying exposure to English and Spanish are able to use language-specific cues in a nonce-word language categorization task. Differences in how, and not only when, a language was acquired may influence listener sensitivity to more difficult cues, and the advantage for phonemic cues may reflect the greater salience of categories unique to each language. Implications for foreign-accent categorization and cross-language speech perception are discussed, and future directions are outlined to better understand how salience varies across language-specific phonemic and phonetic cues.