Factors Affecting Selenium Status in Infants on Parenteral Nutrition Therapy.

INTRODUCTION: Selenium is an essential micronutrient that must be supplemented in infants and young children on exclusive parenteral nutrition (PN). We examined selenium status and clinical factors associated with a deficiency in infants on PN. METHODS: This was a retrospective cohort study of pediatric patients receiving PN with routine monitoring of selenium status. Deficiency was diagnosed using age-based norms of plasma selenium status. Associations between selenium deficiency and the following clinical factors were examined: birthweight status: extremely low birthweight (ELBW) versus very low birthweight (VLBW) versus low birthweight (LBW) versus normal birthweight (NBW), serum albumin status, presence of cholestasis, and co-administration of enteral feeds. RESULTS: A total of 42 infants were included with gestational age [median (interquartile range)] 28 weeks (25,34). The prevalence of selenium deficiency was 80% and the prevalence of albumin deficiency was 87.5%. The odds of selenium deficiency were higher in ELBW infants (odds ratio = 17.84, 95% confidence interval [4.04-78.72], P < 0.001) and VLBW infants (odds ratio = 16.26, 95% confidence interval [1.96-135.04], P < 0.001) compared to NBW infants. The odds of selenium deficiency were 5-fold higher in patients with low serum albumin (odds ratio = 5.33, 95% confidence interval [1.39-20.42], P = 0.015). There were no associations seen between selenium status and presence of cholestasis or co-administration of enteral feeds. CONCLUSION: In this cohort of infants on PN therapy, the main clinical factors associated with selenium deficiency were presence of hypoalbuminemia and history of ELBW or VLBW. These findings support dual measurement of serum albumin and serum selenium to improve interpretation of selenium status.

Feasibility and Outcomes Associated With the Use of 2.6-Fr Double-Lumen PICCs in Neonates.

BACKGROUND: Low birth-weight infants' survival continues to improve and there is increased need to provide secure vascular access. This study examines safety of larger peripherally inserted central catheters (PICCs) that offer greater utility. PURPOSE: To determine feasibility of 2.6-French (Fr) double-lumen PICCs in newborns and compare noninfectious complications such as thrombus formation, catheter breakage, infiltration, and accidental dislodgment and central line-associated bloodstream infection (CLABSI) rate with that of newborn infants treated with 1.9-Fr single- and double-lumen PICCs. METHODS: Infants requiring PICCs were admitted in our 69-bed level IV neonatal intensive care unit from September 2006 to May 2015. Two distinct groups were compared: the 1.9-Fr-(single-lumen [n = 105] and double-lumen [n = 27])-and 2.6-Fr double-lumen PICCs (n = 111). Data obtained included birth weight and weight at insertion, gestational age at birth and corrected gestation age at insertion, indication, catheter days, indication for removal, and complications: noninfectious and infectious. Univariate and multivariate statistical analysis evaluated data. RESULTS: There were no differences regarding gestational age at birth and insertion and indications for placement of 2.6-Fr double-lumen (n =111) and 1.9-Fr both single- and double-lumen (n = 132) PICCs. The same was noted between the groups' complications. Noninfectious complications were more common in PICCs with peripheral tip location in all groups. IMPLICATIONS FOR PRACTICE: Consider use of 2.6-Fr PICCs in a neonatal intensive care unit when the utility of blood administration and sampling is required. IMPLICATIONS FOR RESEARCH: Examine line migration and CLABSI associated with sampling and blood administration.

Manifestations of Cow's-Milk Protein Intolerance in Preterm Infants.

OBJECTIVES: Cow's-milk protein intolerance (CMPI) is poorly recognized in preterm infants. This study examined the clinical events that preceded the diagnosis of CMPI in preterm infants. METHODS: This was a retrospective study of infants in a level-III neonatal intensive care unit of those who received parenteral nutrition (PN) support during a 12-month period. Parameters assessed included birth weight (g), diagnosis, duration and frequency on PN, type of enteral feeds at initiation, and achievement of enteral autonomy. CMPI was diagnosed based on persistent feeding intolerance that resolved after change of feeds from intact protein to a protein hydrolysate or crystalline amino acid formula. RESULTS: Three hundred forty-eight infants with birth weight (median/range) 1618 g (425-5110) received PN. Fifty-one (14%) infants required multiple courses of PN, and 19 of 348 (5%) were diagnosed with CMPI. The requirement for multiple courses on PN versus single course was associated with a high likelihood of CMPI: 14 of 51 versus 5 of 297, P < 0.001. Nine of the 14 infants identified with CMPI were initially diagnosed with necrotizing enterocolitis (NEC) after a median duration of 22 days (19-57) on intact protein feeds. After recovery from NEC, they had persistent feeding intolerance including recurrence of "NEC-like illness" (N = 3) that resolved after change of feeds to a protein hydrolysate or crystalline amino acid formula. CONCLUSIONS: The requirement for multiple courses of PN because of persistent feeding intolerance after recovery from NEC and recurrence of "NEC-like illness" may be a manifestation of CMPI in preterm infants.

Births to Parents with Asian Origins in the United States, 1992-2012.

Despite a remarkable increase in Asian births in the U.S., studies on their birth outcomes have been lacking. We investigated outcomes of births to Asian parents and biracial Asian/White parents in the U.S. From the U.S. birth data (1992-2012), we selected singleton births to Korean, Chinese, Japanese, Filipino, Asian Indian, and Vietnamese. These births were divided into three groups; births to White mother/Asian father, Asian mother/White father, and births to the both ethnic Asian parents. We compared birth outcomes of these 18 subgroups to those of the White mother/White father group. Mean birthweights of births to the Asian parents were significantly lower, ranging 18 g to 295 g less than to the White parents. Compared to the rates of low birthweight (LBW) (4.6%) and preterm birth (PTB) (8.5%) in births to the White parents, births to Filipino parents had the highest rates of LBW (8.0%) and PTB (11.3%), respectively, and births to Korean parents had the lowest rates of both LBW (3.7%) and PTB (5.5%). This pattern of outcomes had changed little with adjustments of maternal sociodemographic and health factors. This observation was similarly noted also in births to the biracial parents, but the impact of paternal or maternal race on birth outcome was different by race/ethnicity. Compared to births to White parents, birth outcomes from the Asian parents or biracial Asian/White parents differed depending on the ethnic origin of Asian parents. The race/ethnicity was the strongest factor for this difference while other parental characteristics hardly explained this difference.

Neonatal and Infant Mortality in Korea, Japan, and the U.S.: Effect of Birth Weight Distribution and Birth Weight-Specific Mortality Rates.

Difference in crude neonatal and infant mortality rates (NMR and IMR) among different countries is due to the differences in its two determinants: birth weight distribution (BWD) and birth weight-specific mortality rates (BW-SMRs). We aimed to determine impact of BWD and BW-SMRs on differences in crude NMR and IMR among Korea, Japan, and the U.S. Our study used the live birth data of the period 2009 through 2010. Crude NMR/IMR are the lowest in Japan, 1.1/2.1, compared to 1.8/3.2, in Korea, and 4.1/6.2, in the U.S., respectively. Japanese had the best BW-SMRs of all birth weight groups compared to the Koreans and the U.S. The U.S. BWD was unfavorable with very low birth weight (< 1,500 g) rate of 1.4%, compared to 0.6% in Korea, and 0.8% in Japan. If Koreans and Japanese had the same BWD as in the U.S., their crude NMR/IMR would be 3.9/6.1 for the Koreans and 1.5/2.5 for the Japanese. If both Koreans and Japanese had the same BW-SMRs as in the U.S., the crude NMR/IMR would be 2.0/3.8 for the Koreans and 2.7/5.0 for the Japanese. In conclusion, compared to the U.S., lower crude NMR or IMR in Japan is mainly attributable to its better BW-SMRs. Koreans had lower crude NMR and IMR, primarily from its favorable BWD. Comparing crude NMR or IMR among different countries should include further exploration of its two determinants, BW-SMRs reflecting medical care, and BWD reflecting socio-demographic conditions.

Retinopathy of prematurity and neurodevelopmental outcome and quality of life at 10 years of age.

Objective: In a cohort of 10-year-old children born extremely preterm, we evaluated the hypothesis that increasing severity of retinopathy of prematurity (ROP) is associated with increasing frequency of unfavorable neurodevelopmental and quality of life outcomes. Study Design: Study participants were classified according to the severity of ROP. At 10 years of age, their neurocognitive abilities, academic achievement, and gross motor function were assessed, and they were evaluated for autism spectrum disorder, anxiety, depression, and quality of life. Results: After adjustment for sample attrition and confounders, only the association with lower quality of life persisted. Increasing severity of visual impairment was associated with worse neurodevelopmental outcomes and lower quality of life. Conclusion: Among extremely preterm children, severity of visual impairment, but not severity of ROP, was associated with adverse neurodevelopmental outcomes at 10 years of age. Both severe ROP and more severe visual impairment were associated with lower quality of life.

Implementation of an Inhaled Nitric Oxide Weaning Protocol and Stewardship in a Level 4 NICU to Decrease Inappropriate Use.

OBJECTIVE: Inhaled nitric oxide (iNO) is an effective but expensive treatment of pulmonary hypertension in newborns, with limited data regarding weaning. Our institution implemented a multidisciplinary iNO weaning protocol and stewardship to reduce inappropriate use of iNO. The objective of this study was to evaluate our institutional iNO usage before and after implementation. METHODS: Single-center study comparing a retrospective control group to a prospective cohort after implementation of an iNO weaning protocol. All infants in the neonatal intensive care unit (NICU) who received iNO during the study timeframe were included. The primary outcome was duration of iNO per course. RESULTS: A total of 47 courses of iNO occurred during the pre-protocol timeframe compared with 37 courses in the post-protocol timeframe. Median iNO usage per course was 149 hours (IQR, 63-243) in the pre-protocol group versus 59 hours (IQR, 37-122) in the post-protocol group (p = 0.008). Length of stay was significantly longer in the pre-protocol group (p = 0.02), likely related to significantly longer ventilator days in the pre-protocol group (p = 0.02). Compliance with initiation of weaning when recommended per the protocol was 72%, and the incidence of successful weaning was 74%. CONCLUSIONS: The implementation of an iNO weaning protocol in the NICU significantly decreased iNO usage by approximately 60% with no notable negative effects.

Extracorporeal membrane oxygenation and term neonatal respiratory failure deaths in the United Kingdom compared with the United States: 1999 to 2005.

OBJECTIVE: To compare national neonatal extracorporeal membrane oxygenation data and deaths from primary respiratory disorders of term neonates between the United Kingdom and the United States from 1999 to 2005. DESIGN: Cross-sectional study. SETTING: National data sets from the United Kingdom and the United States. PATIENTS: Neonatal extracorporeal membrane oxygenation patients submitted to the Extracorporeal Life Support Organization Registry and national birth and death registrations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Meconium aspiration syndrome was the most common indication for extracorporeal membrane oxygenation in the United Kingdom: 50.6% vs. 25.8% in the United States (p < .001). Congenital diaphragmatic hernia was most common indication for extracorporeal membrane oxygenation in the United States: 30.7% vs. 15.4% in the United Kingdom (p < .001).Extracorporeal membrane oxygenation use was greater in the United States than the United Kingdom: rate ratio, 1.81 (95%, confidence interval, 1.64, 2.00). The extracorporeal membrane oxygenation rate decreased over time in the United States (p < .001) but was unchanged for all diagnoses in the United Kingdom (p = .49). The rates of extracorporeal membrane oxygenation use for meconium aspiration syndrome were equivalent in both countries: rate ratio, 0.92 (95% confidence interval, 0.80, 1.07) but greater in the United States for congenital diaphragmatic hernia: rate ratio, 3.60, (95% confidence interval, 2.82, 4.66) and persistent pulmonary hypertension newborn: rate ratio, 4.67 (95% confidence interval, 3.33, 6.74).National neonatal death rates included nonextracorporeal membrane oxygenation + extracorporeal membrane oxygenation death. Meconium aspiration syndrome deaths were equivalent overall between the two countries: rate ratio, 0.99 (95% confidence interval, 0.77, 1.29), but decreased in the United States (p < .001) although not in the United Kingdom (p = .17). Congenital diaphragmatic hernia deaths were more prevalent in the United Kingdom than in the United States: rate ratio, 1.57 (95% confidence interval, 1.34, 1.84). CONCLUSIONS: Extracorporeal membrane oxygenation is used more often in the United States: clinicians seem less willing to offer extracorporeal membrane oxygenation for persistent pulmonary hypertension of the newborn and congenital diaphragmatic hernia in the United Kingdom. In contrast to the United States, no reduction in either extracorporeal membrane oxygenation use or death due to meconium aspiration syndrome was observed in the United Kingdom. Early transfer to a tertiary center is recommended for term neonates with respiratory failure.

Birth outcomes of Koreans by birthplace of infants and their mothers, the United States versus Korea, 1995-2004.

The acculturation effect of immigrant women on birth outcomes varies by race. We examined birth outcomes of three groups of births for the period 1995-2004, USA births to the USA-born Korean mothers, USA births to the non-USA-born Korean mothers, and births in Korea. In singleton USA births to both Korean parents, average birth weight was 3,294 g for the USA-born Korean mothers and 3,323 g for the non-USA-born Korean mothers. However, this difference was not significant, once controlled for other maternal sociodemographic, obstetric and medical factors. Low birth weight and prematurity prevalence were not different by maternal nativity between these two singleton groups. Average birth weight of all births including multiplets in Korea was 3,270 g, compared to 3,297 g for all USA-born infants including multiplets and births either to both or one Korean parents. This difference might have reflected a significantly lower educational attainment of mothers in Korea compared to Korean mothers in the USA. Low birth weight rate was consistently lower in infants born in Korea compared to the USA-born, but this difference became less, 4.2% and 4.6% respectively by 2004. These observations suggest that in the USA acculturation effect of Korean immigrants on birth outcomes is negligible.

Optimal birth weight and term mortality risk differ among different ethnic groups in the U.S.

Among European countries, optimal birth weight at which the mortality is minimal is shown to be different by country. We investigated this difference examining one geopolitical population, the U.S. term live births, born to the five groups of the same ethnic parents; White, Black, Hispanic, North Asian, and South Asian. North Asians and South Asians had more favorable maternal factors for birth weight. Yet, Whites had the highest mean birth weight and South Asians, the lowest. However, neonatal mortality rate in Whites was 0.78 per 1,000 live births, significantly higher than 0.36 and 0.72 per 1,000 live births in North Asians and South Asians, respectively. Other maternal factors hardly explained this ethnic disparity in birth weight or mortality. Optimal birth weight was greatest in Whites (3,890 g), and least in South Asians (3,491 g). However, neonatal mortality at optimal birth weight was significantly lower in North Asians. Adjustment of maternal factors except parental ethnicity changed little of this difference. Optimal birth weight and its mortality differ by ethnicity. On planning the best birth outcome in a population, one should consider the variable mortality risks by ethnicity.

Evaluation of Timing and Dosing of Caffeine Citrate in Preterm Neonates for the Prevention of Bronchopulmonary Dysplasia.

OBJECTIVE: The aim of this study was to evaluate the timing and dosing of caffeine therapy in relation to the development of bronchopulmonary dysplasia (BPD). METHODS: This was a single-center, retrospective cohort study comparing early (days of life 0-2) to late (day of life 3 or greater) caffeine initiation in extremely low birth weight neonates, with a secondary analysis of large (10 mg/kg/day) to small dose (5 mg/kg/day) caffeine. RESULTS: There were 138 patients in the primary timing analysis. The early caffeine group had a lower incidence and reduced odds of the composite outcome of BPD or all-cause mortality, compared with the late caffeine group (64% vs. 88%, respectively; adjusted p < 0.05; adjusted OR 0.36 [95% CI 0.13-0.98]). No statistically significant difference was found between dosing groups (p = 0.29) in the primary outcome; however, there was a lower rate of patent ductus arteriosus requiring treatment (p = 0.05) and decreased likelihood of discharging home on oxygen (p = 0.02) in the large-dose group compared with the small-dose group. CONCLUSIONS: Early caffeine initiation significantly decreased the incidence of BPD or all-cause mortality in extremely low birth weight neonates. Patients receiving large-dose caffeine had improved secondary outcomes, although no difference in BPD was noted. Further studies are needed to determine the optimal dosing of caffeine.

Effects of Chromium on Glucose Tolerance in Infants Receiving Parenteral Nutrition Therapy.

OBJECTIVES: Early hyperglycemia is prevalent in preterm infants receiving parenteral nutrition (PN) therapy. Chromium improves glucose tolerance by potentiating the action of insulin. Therefore, we hypothesized that supplementing PN with chromium would improve glucose tolerance and PN calorie delivery in infants during the first week of life. METHODS: We collected data on neonates receiving PN initiated at birth with chromium (0.2 mcg/kg/d) started either on days 5-7 (group A) vs day 1 (group B) on PN and compared glucose tolerance and PN calorie administration over the first week of life. RESULTS: For similar mean serum glucose concentrations between group A (n = 348) and B (n = 358) (107 ± 48 vs 111 ± 52 mg/dL, P = .3), infants in group B tolerated higher glucose infusion rates and received more PN calories during the first week of life: 8.4 ± 2 vs 8 ± 2 mg/kg/min (P < .001) and 74.8 ± 23 vs 71.5 ± 12 kcal/kg/d (P = .017), respectively. The difference in calories delivered was more pronounced among very low birth weight (VLBW) infants compared with infants >1500 g: 76.5 ± 14 vs 72.4 ± 11 kcal/kg/d (P = .009) and 73.8 ± 27 vs 70.3 ± 12 kcal/kg/d (P = .079), respectively. CONCLUSIONS: PN chromium supplementation resulted in better glucose tolerance and calorie delivery during the first week of life, especially in VLBW infants. This supports chromium's essential role in enhancing glucose tolerance during PN therapy in VLBW infants at risk for early hyperglycemia.

Cognitive Development and Quality of Life Associated With BPD in 10-Year-Olds Born Preterm.

OBJECTIVES: To compare neurocognitive, language, executive function, academic achievement, neurologic and behavioral outcomes, and quality of life at age 10 years in children born extremely preterm who developed bronchopulmonary dysplasia (BPD) to children who did not develop BPD. METHODS: The Extremely Low Gestational Age Newborns study population included 863 children born extremely preterm whose BPD status before discharge was known had an IQ (Differential Ability Scales II [DAS II]) assessment at 10 years. We evaluated the association of BPD with any cognitive (DAS II), executive function (NEuroPSYchological Assessment II), academic achievement (Wechsler Individual Achievement Test-III and Oral and Written Language Scales [OWLS]) as well as social dysfunctions (Social Responsiveness Scale). We used logistic regression models, adjusting for potential confounding factors, to assess the strength of association between the severity of BPD and each outcomes. RESULTS: Three hundred and seventy-two (43%) children were oxygen-dependent at 36 weeks postconception age, whereas an additional 78 (9%) were also oxygen- and ventilator-dependent. IQ scores 2 or more SDs below the expected mean (ie, z scores ≤-2) occurred twice as commonly among children who had BPD as among those who did not. Children with severe BPD consistently had the lowest scores on DAS II, OWLS, Wechsler Individual Achievement Test-III, NEuroPSYchological Assessment II, and Social Responsiveness Scale assessments. CONCLUSIONS: Among 10-year-old children born extremely preterm, those who had BPD were at increased risk of cognitive, language, and executive dysfunctions; academic achievement limitations; social skill deficits; and low scores on assessments of health-related quality of life.

Racial disparity in meconium-stained amniotic fluid and meconium aspiration syndrome in the United States, 1989-2000.

OBJECTIVE: To estimate the prevalence of meconium-stained amniotic fluid and meconium aspiration syndrome, as well as the differences in case fatality from meconium aspiration syndrome, between non-Hispanic black and non-Hispanic white infants. METHODS: We studied non-Hispanic black and non-Hispanic white live births with weights greater than 2.5 kg and gestational ages greater than 35 weeks, using the linked US birth and infant death cohorts for three periods: 1989-1991, 1995-1997, and 1998-2000. We used logistic regression to estimate the risks of meconium-stained amniotic fluid and meconium aspiration syndrome and to estimate the case fatality of meconium aspiration syndrome by maternal race, birth weight, period, and pregnancy complications. RESULTS: Risk of meconium-stained amniotic fluid was 80% higher in non-Hispanic blacks when compared with non-Hispanic whites (birth weight-adjusted odds ratio [OR], 1.81, 95% confidence interval [CI] 1.80, 1.82). The prevalence of pregnancy complications did not explain this racial disparity. Risk of meconium aspiration syndrome in non-Hispanic blacks was 67% higher when compared with non-Hispanic whites (birth weight-adjusted OR 1.67, 95% CI 1.64, 1.70). The case fatality rate of meconium aspiration syndrome was similar between non-Hispanic blacks and non-Hispanic whites in the three periods, with rates of 15.5, 15.2, and 11.2 per 1000 in non-Hispanic blacks and 13.5, 11.2, and 10.1 per 1000 in non-Hispanic whites in 1989-1991, 1995-1997, and 1998-2000, respectively. CONCLUSION: Our results suggest that when compared with non-Hispanic whites, non-Hispanic blacks are at significantly greater risk for meconium-stained amniotic fluid and meconium aspiration syndrome but not for meconium aspiration syndrome case fatality.

Early blood gas predictors of bronchopulmonary dysplasia in extremely low gestational age newborns.

Aim. To determine among infants born before the 28th week of gestation to what extent blood gas abnormalities during the first three postnatal days provide information about the risk of bronchopulmonary dysplasia (BPD). Methods. We studied the association of extreme quartiles of blood gas measurements (hypoxemia, hyperoxemia, hypocapnea, and hypercapnea) in the first three postnatal days, with bronchopulmonary dysplasia, among 906 newborns, using multivariable models adjusting for potential confounders. We approximated NIH criteria by classifying severity of BPD on the basis of the receipt of any O2 on postnatal day 28 and at 36 weeks PMA and assisted ventilation. Results. In models that did not adjust for ventilation, hypoxemia was associated with increased risk of severe BPD and very severe BPD, while infants who had hypercapnea were at increased risk of very severe BPD only. In contrast, infants who had hypocapnea were at reduced risk of severe BPD. Including ventilation for 14 or more days eliminated the associations with hypoxemia and with hypercapnea and made the decreased risk of very severe BPD statistically significant. Conclusions. Among ELGANs, recurrent/persistent blood gas abnormalities in the first three postnatal days convey information about the risk of severe and very severe BPD.