Screening for Delayed Thyroid Stimulation Hormone Rise and Atypical Congenital Hypothyroidism in Infants Born Very Preterm and Infants with Very Low Birth Weight.

OBJECTIVE: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age. STUDY DESIGN: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 µIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database. RESULTS: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 µIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 µIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 µIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity. CONCLUSIONS: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy.

The impact of an early intervention home-based program on body composition in preterm-born preschoolers with very low birth weight.

Background and aims: Early child interventions focused on the family prevented neurodevelopmental and behavioral delays and can provide more knowledge regarding responsive feeding, thus creating learning opportunities to promote better quality nutrition and preventing failure to thrive. The aim is to verify the impact of a continuous program of early home-based intervention on the body composition of preschool infants who were born preterm with very low birth weight (VLBW). Methods: This is a longitudinal analysis from a randomized controlled trial, including VLBW preterm children, born in a tertiary hospital in Southern Brazil and followed up at the high-risk institutional ambulatory clinic. Participants were divided into the intervention group (IG): skin-to-skin care with the mother (kangaroo care), breastfeeding policy, and tactile-kinesthetic stimulation by mothers until hospital discharge. Subsequently, they received a program of early intervention with orientation and a total of 10 home visits, independently from the standard evaluation and care that was performed following the 18 months after birth; conventional group (CG): standard care according to the routine of the newborn intensive care unit (NICU), which includes kangaroo care, and attending to their needs in the follow-up program. Body composition estimation was performed using bioelectrical impedance analyses (BIA), and physical activity and feeding practices questionnaires were evaluated at preschool age, as well as anthropometric measurements and biochemical analysis. Results: Data of 41 children at 4.6 ± 0.5 years old were evaluated (CG n = 21 and IG n = 20). Body weight, height, body mass index, waist and arm circumferences, and triceps and subscapular skinfold did not differ between groups. The IG presented higher segmented fat-free mass (FFM) when compared to the CG (right arm FFM: 0.74 vs. 0.65 kg, p = 0.040; trunk FFM: 6.86 vs. 6.09 kg, p = 0.04; right leg FFM: 1.91 vs. 1.73 kg, p = 0.063). Interaction analyses showed that segmented FFM and FFM Index were associated with higher iron content in the IG. In the CG, interaction analyses showed that increased visceral fat area was associated with higher insulin resistance index. Conclusion: An early intervention protocol from NICU to a home-based program performed by the mothers of VLBW preterm children of low-income families presents a small effect on FFM.

Bifidobacteriumlongum subsp. infantis EVC001 Administration Is Associated with a Significant Reduction in the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants.

OBJECTIVE: To assess the effects of Bifidobacteriumlongum subsp. infantis EVC001 (Binfantis EVC001) administration on the incidence of necrotizing enterocolitis (NEC) in preterm infants in a single level IV neonatal intensive care unit (NICU). STUDY DESIGN: Nonconcurrent retrospective analysis of 2 cohorts of very low birth weight (VLBW) infants not exposed and exposed to Binfantis EVC001 probiotic at Oregon Health & Science University from 2014 to 2020. Outcomes included NEC incidence and NEC-associated mortality, including subgroup analysis of extremely low birth weight (ELBW) infants. Log-binomial regression models were used to compare the incidence and risk of NEC-associated outcomes between the unexposed and exposed cohorts. RESULTS: The cumulative incidence of NEC diagnoses decreased from 11.0% (n = 301) in the no EVC001 (unexposed) cohort to 2.7% (n = 182) in the EVC001 (exposed) cohort (P < .01). The EVC001 cohort had a 73% risk reduction of NEC compared with the no EVC001 cohort (adjusted risk ratio, 0.27; 95% CI, 0.094-0.614; P < .01) resulting in an adjusted number needed to treat of 13 (95% CI, 10.0-23.5) for Binfantis EVC001. NEC-associated mortality decreased from 2.7% in the no EVC001 cohort to 0% in the EVC001 cohort (P = .03). There were similar reductions in NEC incidence and risk for ELBW infants (19.2% vs 5.3% [P < .01]; adjusted risk ratio, 0.28; 95% CI, 0.085-0.698 [P = .02]) and mortality (5.6% vs 0%; P < .05) in the 2 cohorts. CONCLUSIONS: In this observational study of 483 VLBW infants, Binfantis EVC001 administration was associated with significant reductions in the risk of NEC and NEC-related mortality. Binfantis EVC001 supplementation may be considered safe and effective for reducing morbidity and mortality in the NICU.

Evaluating Care in Safety Net Hospitals: Clinical Outcomes and Neonatal Intensive Care Unit Quality of Care in California.

OBJECTIVES: To examine the characteristics of safety net (sn) and non-sn neonatal intensive care units (NICUs) in California and evaluate whether the site of care is associated with clinical outcomes. STUDY DESIGN: This population-based retrospective cohort study of 34 snNICUs and 104 non-snNICUs included 22 081 infants born between 2014 and 2018 with a birth weight of 401-1500 g or gestational age of 22-29 weeks. Quality of care as measured by the Baby-MONITOR score and rates of survival without major morbidity were compared between snNICUs and non-snNICUs. RESULTS: Black and Hispanic infants were cared for disproportionately in snNICUs, where care and outcomes varied widely. We found no significant differences in Baby-Measure Of Neonatal InTensive care Outcomes Research (MONITOR) scores (z-score [SD]: snNICUs, -0.31 [1.3]; non-snNICUs, 0.03 [1.1]; P = .1). Among individual components, infants in snNICUs exhibited lower rates of human milk nutrition at discharge (-0.64 [1.0] vs 0.27 [0.9]), lower rates of no health care-associated infection (-0.27 [1.1] vs 0.14 [0.9]), and higher rates of no hypothermia on admission (0.39 [0.7] vs -0.25 [1.1]). We found small but significant differences in survival without major morbidity (adjusted rate, 65.9% [95% CI, 63.9%-67.9%] for snNICUs vs 68.3% [95% CI, 67.0%-69.6%] for non-snNICUs; P = .02) and in some of its components; snNICUs had higher rates of necrotizing enterocolitis (3.8% [3.4%-4.3%] vs 3.1% [95% CI, 2.8%-3.4%]) and mortality (95% CI, 7.1% [6.5%-7.7%] vs 6.6% [6.2%-7.0%]). CONCLUSIONS: snNICUs achieved similar performance as non-snNICUs in quality of care except for small but significant differences in any human milk at discharge, infection, hypothermia, necrotizing enterocolitis, and mortality.

Intracranial Hemorrhage and 2-Year Neurodevelopmental Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To determine the incidence, timing, progression, and risk factors for intracranial hemorrhage (ICH) in infants 240/7 to 276/7 weeks of gestational age and to characterize the association between ICH and death or neurodevelopmental impairment (NDI) at 2 years of corrected age. STUDY DESIGN: Infants enrolled in the Preterm Erythropoietin Neuroprotection Trial had serial cranial ultrasound scans performed on day 1, day 7-9, and 36 weeks of postmenstrual age to evaluate ICH. Potential risk factors for development of ICH were examined. Outcomes included death or severe NDI as well as Bayley Scales of Infant and Toddler Development, 3rd Edition, at 2 years of corrected age. RESULTS: ICH was identified in 38% (n = 339) of 883 enrolled infants. Multiple gestation and cesarean delivery reduced the risk of any ICH on day 1. Risk factors for development of bilateral Grade 2, Grade 3, or Grade 4 ICH at day 7-9 included any ICH at day 1; 2 or more doses of prenatal steroids decreased risk. Bilateral Grade 2, Grade 3, or Grade 4 ICH at 36 weeks were associated with previous ICH at day 7-9. Bilateral Grade 2, any Grade 3, and any Grade 4 ICH at 7-9 days or 36 weeks of postmenstrual age were associated with increased risk of death or severe NDI and lower Bayley Scales of Infant and Toddler Development, 3rd Edition, scores. CONCLUSIONS: Risk factors for ICH varied by timing of bleed. Bilateral and increasing grade of ICH were associated with death or NDI in infants born extremely preterm.

Prolonged intravenous immunoglobulin treatment in very low birth weight infants with late onset sepsis.

BACKGROUND: Neonatal infections are a leading cause of morbi-mortality despite advances in antimicrobials and neonatal care. Preterm infants have greater susceptibility to sepsis due to an immature immune system and lower immunoglobulin levels. Intravenous immunoglobulins (IVIG) have been used in several studies as an adjuvant treatment to improve this physiological immune deficiency, with different outcomes. METHODS: Very low birth weight (VLBW) infants who developed sepsis in the neonatal ICU were studied. They were randomly divided in 2 groups: one group was treated with antibiotics (Group I), and the other received antibiotics plus a 500 mg/kg/day of IVIG during 7 days (Group II). Serum IgG concentration was determined at initiation, during and after treatment Group I, and daily during the 7 days of therapy in Group II. RESULTS: The baseline IgG concentration in group II was 486 g/dL, and increased to 852 mg/dL after the first dose of IVIG (p < 0.01). After the seventh day of infusion a mean IgG level of 1898 mg/dL was achieved. A direct correlation (r = 0.94) between IgG concentration and days of treatment was observed. Blood cultures were positive in 70% of the infants in group I and 75.5% in group II. Staphylococcus epidermidis was the most frequent isolated bacteria in blood cultures. The lethality rate was 25.0% in group I and 5.0% in Group II (p < 0.03). We did not observe collateral effects with the administration of IVIG. CONCLUSIONS: Prolonged therapy with IVIG seems to be safe and effective as an adjuvant treatment in VLBW infants with sepsis.

Predictors of Prolonged Breast Milk Provision to Very Low Birth Weight Infants.

OBJECTIVE: To identify factors associated with prolonged maternal breast milk (BM) provision in very low birth weight (VLBW) infants. STUDY DESIGN: This was a cohort study of VLBW infants who initially received maternal BM and were born at one of 197 neonatal intensive care units managed by the Pediatrix Medical Group from 2010 to 2012. We used multivariable logistic regression to identify demographic, clinical, and maternal factors associated with provision of maternal BM on day of life (DOL) 30 and at discharge. RESULTS: Median gestational age for all infants was 28 weeks (25th, 75th percentiles: 26, 30), and median maternal age was 28 years (23, 33). Of 8806 infants, 6261 (71%) received maternal BM on DOL 30, and 4003 of 8097 (49%) received maternal BM at discharge to home. Predictors of maternal BM provision at DOL 30 included increased maternal age, white maternal race, absence of history of necrotizing enterocolitis or late-onset sepsis, higher household income, lower education level, lack of donor BM exposure, and lower gestational age. CONCLUSIONS: Our results suggest that maternal-infant demographic and clinical factors and household neighborhood socioeconomic characteristics were associated with provision of maternal BM at 30 postnatal days to VLBW infants. Identification of these factors allows providers to anticipate mothers' needs and develop tailored interventions designed to improve rates of prolonged maternal BM provision and infant outcomes.

Breastfeeding Trends Among Very Low Birth Weight, Low Birth Weight, and Normal Birth Weight Infants.

OBJECTIVE: To examine the change in breastfeeding behaviors over time, among low birth weight (LBW), very low birth weight (VLBW), and normal birth weight (NBW) infants using nationally representative US data. STUDY DESIGN: Univariate statistics and bivariate logistic models were examined using the Early Child Longitudinal Study-Birth Cohort (2001) and National Study of Children's Health (2007 and 2011/2012). RESULTS: Breastfeeding behaviors improved for infants of all birth weights from 2007 to 2011/2012. In 2011/2012, a higher percentage of VLBW infants were ever breastfed compared with LBW and NBW infants. In 2011/2012, LBW infants had a 28% lower odds (95% CI, 0.57-0.92) of ever breastfeeding and a 52% lower odds (95% CI, 0.38-0.61) of breastfeeding for ≥6 months compared with NBW infants. Among black infants, a larger percentage of VLBW infants were breastfed for ≥6 months (26.2%) compared with LBW infants (14.9%). CONCLUSIONS: Breastfeeding rates for VLBW and NBW infants have improved over time. Both VLBW and NBW infants are close to meeting the Healthy People 2020 ever breastfeeding goal of 81.9%. LBW infants are farther from this goal than VLBW infants. The results suggest a need for policies that encourage breastfeeding specifically among LBW infants.

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect.

OBJECTIVE: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. STUDY DESIGN: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. RESULTS: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. CONCLUSION: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. TRIAL REGISTRATION: isrctn.org: ISRCTN53107700.

Rehospitalization Through Childhood and Adolescence: Association with Neonatal Morbidities in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the impact of major neonatal morbidities on the risks for rehospitalization in children and adolescents born of very low birth weight. STUDY DESIGN: An observational study was performed on data of the Israel Neonatal Network linked together with the Maccabi Healthcare Services medical records. After discharge from the neonatal intensive care unit, 6385 infants of very low birth weight born from 1995 to 2012 were registered with Maccabi Healthcare Services and formed the study cohort. Multivariable negative binomial regression models were calculated to estimate the adjusted relative risk (aRR) and 95% CI for hospitalization. RESULTS: Up to 18 years following discharge, 3956 infants were hospitalized at least once. The median age of follow-up was 10.7 years with total of follow-up of 67 454 patient years and 10 895 hospitalizations. The risks for rehospitalization were increased significantly for each of the neonatal morbidities: surgical necrotizing enterocolitis (NEC), aRR 2.71 (95% CI 2.08-3.53), intraventricular hemorrhage grades 3-4, 2.13 (1.85-2.46), periventricular leukomalacia (PVL), 1.83 (1.58-2.13), bronchopulmonary dysplasia, 1.94 (1.72-2.17), and retinopathy of prematurity stages 3-4, 1.59 (1.36-1.85). During the first 4 years, children with surgically treated NEC, intraventricular hemorrhage, PVL, or bronchopulmonary dysplasia had 1.5- to 2.5-fold greater risks for hospitalization compared with those without the specific morbidity. In the 11th-14th and 15th-18th years, respectively, surgically treated NEC was associated with a 3.05 (1.32-7.04) and 3.26 (0.99-10.7) aRR for hospitalization, and PVL was associated with a 2.67 (1.79-3.97) and 3.47 (2.03-5.92) aRR for hospitalization. CONCLUSIONS: Specific major neonatal morbidities as well as the number of morbidities were associated with excess risks of rehospitalization through childhood and adolescence.

Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants.

OBJECTIVE: To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection. STUDY DESIGN: We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses. RESULTS: Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period. CONCLUSION: We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633.

Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age.

OBJECTIVE: To assess and compare long-term pulmonary outcomes in former preterm-born, very low birth weight (VLBW) children with and without bronchopulmonary dysplasia (BPD) born in the surfactant era. STUDY DESIGN: Pulmonary function tests (ie, spirometry, body plethysmography, and gas transfer testing) were performed in children with a history of VLBW and BPD (n = 28) and compared with a matched preterm-born VLBW control group (n = 28). Medical history was evaluated by questionnaire. RESULTS: At time of follow-up (mean age, 9.5 years), respiratory symptoms (36% vs 8%) and receipt of asthma medication (21% vs 0%) were significantly more frequent in the preterm-born children with previous BPD than in those with no history of BPD. The children with a history of BPD had significantly lower values for forced expiratory volume in 1 second (z-score -1.27 vs -0.4; P = .008), forced vital capacity (z-score -1.39 vs -0.71 z-score; P = .022), and forced expiratory flow rate at 50% of forced vital capacity (z-score -2.21 vs -1.04; P = .048) compared with the preterm control group. CONCLUSION: Preterm-born children with a history of BPD are significantly more likely to have lung function abnormalities, such as airway obstruction and respiratory symptoms, at school age compared with preterm-born children without BPD.

Concurrent bloodstream infections in infants with necrotizing enterocolitis.

OBJECTIVE: To determine the incidence, microbiology, risk factors, and outcomes related to bloodstream infections (BSIs) concurrent with the onset of necrotizing enterocolitis (NEC). STUDY DESIGN: We performed a retrospective review of all cases of NEC in a single center over 20 years. BSI was categorized as "NEC-associated" if it occurred within 72 hours of the diagnosis of NEC and "post-NEC" if it occurred >72 hours afterwards. Demographics, hospital course data, microbiologic data, and outcomes were compared via univariate and multivariate analyses. RESULTS: NEC occurred in 410 infants with mean gestational age and birth weight of 29 weeks and 1290 g, respectively; 158 infants were diagnosed with at least one BSI; 69 (43.7%) with NEC-associated BSI, and 89 (56.3%) with post-NEC BSI. Two-thirds of NEC-associated BSI were due to gram-negative bacilli compared with 31.9% of post-NEC BSI (OR: 4.27; 95% CI: 2.02, 9.03) and 28.5% of all BSI in infants without NEC (OR: 5.02; 95% CI: 2.82, 8.96). Infants with NEC-associated BSI had higher odds of requiring surgical intervention (aOR: 3.51; 95% CI: 1.98, 6.24) and death (aOR: 2.88; 95% CI: 1.39, 5.97) compared with those without BSI. CONCLUSIONS: BSI is a common, underappreciated complication of NEC occurring concurrent with the onset of disease and afterwards. The microbiologic etiology of NEC-associated BSI is different from post-NEC and late-onset BSI in infants without NEC with a predominance of gram-negative bacilli. Infants with NEC-associated BSI are significantly more likely to die than those with post-NEC BSI and NEC without BSI.

Hypothermia and early neonatal mortality in preterm infants.

OBJECTIVE: To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. STUDY DESIGN: This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 °C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. RESULTS: Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 °C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 °C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 °C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08-2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). CONCLUSION: Simple interventions, such as maintaining DR temperature >25 °C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival.

Quality of life at age 18 years after extremely preterm birth in the post-surfactant era.

OBJECTIVES: To assess the self-reported quality of life, health status, self-esteem, and functional outcomes at age 18 years of extremely preterm (EP; <28 weeks gestation) or extremely low birth weight (ELBW; birth weight <1000 g) adolescents born in 1991-1992 compared with normal birth weight (birth weight >2499 g) controls, and, within the EP/ELBW cohort, to assess whether these outcomes are related to gestational age or birth weight. STUDY DESIGN: Self-reported measures of quality of life, health status, self-esteem, and functional outcomes were obtained at age 18 years from a geographic cohort of all survivors born EP/ELBW in 1991-1992 in the state of Victoria, Australia, along with matched normal birth weight controls. RESULTS: Data were available from 194 EP/ELBW and 148 control adolescents. EP/ELBW adolescents reported similar overall quality of life, health status, and self-esteem as controls (P > .05). Birth at younger gestational age or lower birth weight were not related to poorer quality of life within the EP/ELBW cohort (P > .05). EP/ELBW adolescents reported less physical activity (OR, 0.5; 95% CI, 0.3-0.8; P < .01), sexual activity (OR, 0.6; 95% CI, 0.4-0.9; P = .01), and alcohol intake (OR, 0.5; 95% CI, 0.3-0.8; P = .01) compared with controls. Other aspects of risk-taking behavior were similar in the 2 groups (P > .05). CONCLUSION: EP/ELBW individuals born after the introduction of exogenous surfactant are transitioning well into young adulthood, despite the fact that more of the tiniest and most immature infants survive than ever before. They report similar quality of life, self-esteem, and social and risk-taking behaviors as controls.

Self and parent perspectives on health-related quality of life of adolescents born very preterm.

OBJECTIVES: To test whether health-related quality of life (HRQL) based on societal standards differs between very low birth weight/very preterm (VLBW/VP) and full-term (FT) adolescents using self and parent proxy reports. Also, to examine whether self and parent reported HRQL is explained by indicators of objective functioning in childhood. STUDY DESIGN: This prospective cohort study followed 260 VLBW/VP adolescents, 12 VLBW/VP adolescents with disability, and 282 FT adolescents. Objective functioning was assessed at 8.5 years; HRQL was assessed at 13 years with the Health Utilities Index Mark 3 (HUI3). RESULTS: Adolescents reported more functional impairment than their parents especially in the psychological aspects of health. The mean difference in HUI3 multi-attribute utility scores between FT and VLBW/VP adolescents was small (parents: 0.91 [95% CI, 0.90, 0.92] vs 0.88 [95% CI, 0.86, 0.90]; adolescents: 0.87 [95% CI, 0.85, 0.89] vs 0.84 [95% CI, 0.82, 0.86]), but high for VLBW/VP adolescents with disabilities (0.18, 95% CI, -0.04, 0.40). Objective function did not predict HRQL in FT adolescents but contributed to prediction of HRQL in VLBW/VP adolescents without disabilities. Different indicators of objective functioning were important for adolescent vs parent reports. More variation in HUI3 scores was explained by objective function in VLBW/VP parent reports compared with adolescent reports (25% vs 18%). CONCLUSIONS: VLBW/VP adolescents reported poorer HRQL than their FT peers in early adolescence. Improvement in HRQL as VLBW/VP children grow up is, at least partly, explained by exclusion of the most disabled in self reports by VLBW/VP adolescents and the use of different reference points by adolescents compared with parents.

Target fortification of breast milk with fat, protein, and carbohydrates for preterm infants.

OBJECTIVES: Fortification of breast milk is an accepted practice for feeding very low birth weight infants, however, fixed dosage enhancement does not address variations in native breast milk. This could lead to deficiencies in calories and macronutrients. We therefore established the infrastructure for target fortification in breast milk by measuring and adjusting fat, protein, and carbohydrate content daily. We analyzed nutrient intake, growth, and safety variables. STUDY DESIGN: Each 12-hour batch of breast milk was analyzed using near-infrared spectroscopy. Macronutrients were individually added to routine fortification to achieve final contents for fat (4.4 g), protein (3 g), and carbohydrates (8.8 g) (per 100 mL). Fully breast milk fed healthy very low birth weight infants (<32 weeks) were fed the fortified breast milk for at least 3 weeks. Matched pair analysis of 20 infants fed routinely fortified breast milk was performed using birth weight, gestational age, and postnatal age. RESULTS: All 650 pooled breast milk samples required at least 1 macronutrient adjusted. On average, 0.3 ± 0.4 g of fat, 0.7 ± 0.2 g of protein, and 1.2 ± 0.2 g of carbohydrate were added. Biochemistry was normal in the 10 target fortified infants (birth weight: 860 ± 309 g, 26.3 ± 1.6 weeks gestational age); weight gain was 19.9 ± 2.7 g/kg/d; and milk intake was 147 ± 5 mL/kg/d (131 ± 16 kcal/kg/d). Osmolality of fortified breast milk was 436 ± 13 mOsmol/kg. Matched pair analysis of infants indicated a higher milk intake (155 ± 5 mL/kg/d) but similar weight gain (19.7 ± 3.3 g/kg/d). No adverse event was observed. The linear relationship between milk intake and weight gain observed in study babies but not seen in matched controls may be related to the variable composition of breast milk. CONCLUSIONS: Daily target fortification can be safely implemented in clinical routine and may improve growth.

Safety and efficacy of early parenteral lipid and high-dose amino acid administration to very low birth weight infants.

OBJECTIVE: To assess the efficacy and safety of early parenteral lipid and high-dose amino acid (AA) administration from birth onwards in very low birth weight (VLBW, birth weight <1500 g) infants. STUDY DESIGN: VLBW infants (n = 144; birth weight 862 ± 218 g; gestational age 27.4 ± 2.2 weeks) were randomized to receive 2.4 g of AA kg(-1) · d(-1) (control group), or 2.4 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (AA + lipid group), or 3.6 g AA kg(-1) · d(-1) plus 2-3 g lipids kg(-1) · d(-1) (high AA + lipid group) from birth onwards. The primary outcome was nitrogen balance. The secondary outcomes were biochemical variables, urea rate of appearance, growth rates, and clinical outcome. RESULTS: The nitrogen balance on day 2 was significantly greater in both intervention groups compared with the control group. Greater amounts of AA administration did not further improve nitrogen balance compared with standard AA dose plus lipids and was associated with high plasma urea concentrations and high rates of urea appearance. No differences in other biochemical variables, growth, or clinical outcomes were observed. CONCLUSIONS: In VLBW infants, the administration of parenteral AA combined with lipids from birth onwards improved conditions for anabolism and growth, as shown by improved nitrogen balance. Greater levels of AA administration did not further improve the nitrogen balance but led to increased AA oxidation. Early lipid initiation and high-dose AA were well tolerated.

Indomethacin prophylaxis to prevent intraventricular hemorrhage: association between incidence and timing of drug administration.

OBJECTIVE: To test the hypothesis that administration of indomethacin prophylaxis before 6 hours of life results in a lower incidence of intraventricular hemorrhage (IVH) compared with administration after 6 hours of life, and that the effects of early prophylaxis depend on gestational age (GA) and sex in very low birth weight infants (birth weight <1250 g). STUDY DESIGN: Very low birth weight infants admitted to our neonatal intensive care unit between 2003 and 2010 who received indomethacin prophylaxis were analyzed retrospectively. Exclusion criteria included unknown time of indomethacin prophylaxis, death at <12 hours of life, congenital anomalies, and unavailable head ultrasound report. Infants were dichotomized based on the timing of indomethacin prophylaxis (<6 hours or >6 hours of life) to compare incidence of IVH all grades and severe (grade 3-4) IVH. Secondary analyses examined the effects of the time of indomethacin prophylaxis initiation by GA and sex on the incidence of IVH. RESULTS: A total of 868 infants (431 males and 437 females) met the criteria for analysis. Indomethacin prophylaxis was given at <6 hours of life in 730 infants and at >6 hours of life to 168 infants. The 2 groups differed with respect to antenatal steroid exposure, GA, outborn prevalence, and pneumothoraces. After multivariate analysis, there were no between-group differences in all-grade or severe IVH. However, females, but not males, treated at <6 hours of life had a lower incidence of severe IVH (P < .05), particularly at lower GAs. CONCLUSION: Prophylactic indomethacin administered before 6 hours of life is not associated with lower incidence of IVH.