Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).

Oxygen management among infants in neonatal units in sub-Saharan Africa: a cross-sectional survey.

OBJECTIVES: To provide more comprehensive data on the management of oxygen supplementation in neonates in sub-Saharan Africa. STUDY DESIGN: An online survey on the management of oxygen supplementation for infants in neonatal units was sent to 278 healthcare personnel in sub-Saharan Africa. RESULTS: One hundred and nine responses from 82 neonatal care units in 54% (26/48) sub-Saharan African countries were received. All units had the capacity to provide oxygen supplementation. However, only 50% (38/76) had access to blend oxygen with medical air and 1% (1/75) had the capacity to blend oxygen/air for every infant. Although 96% (72/75) of units could monitor oxygen saturation, monitoring was mostly intermittent and only 32% (24/75) were able to monitor oxygen saturation in every infant receiving oxygen supplementation. CONCLUSIONS: Findings indicate that oxygen supplementation is inadequately managed in neonatal units in sub-Saharan Africa, which may put infants at risk of developing severe ROP.

Management of neonatal jaundice in low- and middle-income countries.

Abbreviations: ABE: acute bilirubin encephalopathy; ABR: auditory evoked brainstem response; BIND: bilirubin-induced neurological dysfunction; EBT: exchange blood transfusions; HIC: high-income countries; KSD: kernicterus spectrum disorder; LED: light-emitting diode; LMIC: low- and middle-income countries; SNH: severe neonatal jaundice or hyperbilirubinaemia; TcB: transcutaneous bilirubinometry; TSB: total serum bilirubin.

Lack of social support as measured by the Family Resource Scale screening tool is associated with early adverse cognitive outcome in extremely low birth weight children.

OBJECTIVE: Extremely low birth weight children are at high risk for cognitive impairment. STUDY DESIGN: Cognitive outcome of extremely low birth weight children participating in a Neonatal Research Network, randomized trial was evaluated at 18 and 30 months corrected age using the Bayley Scales of Infant Development, 2nd ed. Family resources and social support were assessed using a Family Resource Scale parent questionnaire. Regression analysis was used to determine independent demographic, medical, and family resource factors influencing longitudinal cognitive outcome. RESULT: Higher Family Resource Scale scores at 18 months were associated with greater improvement in cognitive scores between 18 and 30 months. Cognitive outcome was most adversely affected in children whose families had the least resources and social support. The adverse effect of poor social support was independent of family income. CONCLUSION: Poor interpersonal social support has an independent, adverse impact on cognitive outcomes of extremely low birth weight infants.

Filtered sunlight versus intensive electric powered phototherapy in moderate-to-severe neonatal hyperbilirubinaemia: a randomised controlled non-inferiority trial.

BACKGROUND: Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia. METHODS: We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 µmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%. FINDINGS: Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 µW/cm2/nm (IQR 21·4-56·4) in the FSPT group and 50·4 µW/cm2/nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates. INTERPRETATION: FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants. FUNDING: Thrasher Research Fund and National Center for Advancing Translational Sciences.

Preterm Neuroimaging and School-Age Cognitive Outcomes.

BACKGROUND AND OBJECTIVES: Children born extremely preterm are at risk for cognitive difficulties and disability. The relative prognostic value of neonatal brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear. Our objectives were to relate near-term conventional brain MRI and early and late CUS to cognitive impairment and disability at 6 to 7 years among children born extremely preterm and assess prognostic value. METHODS: A prospective study of adverse early and late CUS and near-term conventional MRI findings to predict outcomes at 6 to 7 years including a full-scale IQ (FSIQ) <70 and disability (FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated associations of neuroimaging with outcomes, adjusting for perinatal-neonatal factors. RESULTS: A total of 386 children had follow-up. In unadjusted analyses, severity of white matter abnormality and cerebellar lesions on MRI and adverse CUS findings were associated with outcomes. In full regression models, both adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0-129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1-6.7) remained associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI 3.6-111) were associated with FSIQ <70. Predictive accuracy of stepwise models was not substantially improved with the addition of neuroimaging. CONCLUSIONS: Severe but rare adverse late CUS findings were most strongly associated with cognitive impairment and disability at school age, and significant cerebellar lesions on MRI were associated with disability. Near-term conventional MRI did not substantively enhance prediction of severe early school-age outcomes.

A Randomized Clinical Trial of Umbilical Cord Milking vs Delayed Cord Clamping in Preterm Infants: Neurodevelopmental Outcomes at 22-26 Months of Corrected Age.

OBJECTIVE: To compare the effect of umbilical cord milking vs delayed cord clamping (DCC) on neurodevelopmental and health outcomes in very preterm infants at 22-26 months of corrected age. STUDY DESIGN: Neurodevelopmental outcomes at 2 years of age were assessed using the Bayley Scales of Infant Development, third edition, and a standardized neurologic examination. Data regarding pulmonary morbidities, neurosensory impairments, and hospitalizations were obtained by parental interview. Intention-to-treat was used for primary analyses. RESULTS: Of the 197 infants enrolled in the original study there were 15 deaths, 5 in the umbilical cord milking group and 10 in DCC group. Of the remaining infants, 135 (74%) were assessed at 22-26 months of corrected age. Demographics in umbilical cord milking (n = 70) and DCC (n = 65) groups were similar. Infants randomized to umbilical cord milking at birth had significantly higher cognitive and language composite scores, and were less likely to have a cognitive composite score of <85 (4% vs 15%; P = .04). Motor function was similar in both groups. There were no differences in the incidences of mild or moderate to severe neurodevelopmental impairment, hearing or visual impairments, pulmonary morbidities, or rehospitalizations between the 2 groups. CONCLUSIONS: Infants randomized to umbilical cord milking had higher language and cognitive scores compared with those randomized to DCC. There was no difference in rates of mild or moderate to severe neurodevelopmental impairment. TRIAL REGISTRATION: clinicaltrials.gov: NCT01434732.

Behavioral Problems and Socioemotional Competence at 18 to 22 Months of Extremely Premature Children.

BACKGROUND: Behavior and socioemotional development are crucial aspects of child development . METHODS: A total of 2505 children born at <27 weeks' gestation was evaluated at 18 to 22 months' corrected age between January 1, 2008 and December 12, 2012 (86% follow-up). The Brief Infant and Toddler Social and Emotional Assessment was used to evaluate behavioral and socioemotional problems. Cognition and language were evaluated by using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Logistic regression analysis was used to evaluate for perinatal and demographic factors associated with behavioral problems (≥75th percentile) and delayed socioemotional competence (≤15th percentile). Structural equation modeling with bootstrapping was used to identify possible associated risk factors and Bayley-III scores as mediators. RESULTS: Thirty-five percent (873) of children had behavioral problems, and 26% (637) displayed deficits in socioemotional competence. Male sex, public insurance, mothers with less than a high school education, and lower maternal age were associated with behavioral problems. Deficits in competence were associated with lower birth weight, public insurance, mothers with less than a high school education, and abnormal neuromotor exam. Bayley-III language and cognitive scores were significant mediators of the relationships between risk factors and both behavioral and competence scores (P < .05). CONCLUSIONS: Extremely premature children are at risk for behavioral problems and deficits in socioemotional competence. Sociodemographic factors were associated with both socioemotional competence and behavioral problems. Deficits in socioemotional competence were also associated with neuromotor abnormalities and cognitive and language function.

ABM Clinical Protocol #10: Breastfeeding the Late Preterm (34-36 6/7 Weeks of Gestation) and Early Term Infants (37-38 6/7 Weeks of Gestation), Second Revision 2016.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

Intubation Attempts Increase the Risk for Severe Intraventricular Hemorrhage in Preterm Infants-A Retrospective Cohort Study.

OBJECTIVE: To evaluate whether neonates exposed to multiple intubation attempts within the first 4 days after birth have an increased incidence of intraventricular hemorrhage (IVH). STUDY DESIGN: This is a retrospective cohort study of infants intubated during the first 4 days after birth. Infants had birth weights (BWs) less than 1500 g and were admitted to the neonatal intensive care unit (NICU) at the University of California, San Diego, between January 1, 2005, and July 30, 2009. A subgroup analysis was done for infants with BW less than 750 g. RESULTS: A total of 308 infants with BW <1500 g, including 102 with a BW <750 g, were intubated within the first 4 days of life. The number of intubation attempts was significantly greater in infants with a BW <750 g who had severe IVH compared with those with mild or no IVH (OR 1.395, 95% CI 1.090-1.786, P = .008). For infants with BW <1500 g, the number of intubation attempts in the delivery room was significantly greater for infants with severe IVH (OR 1.317, 95% CI 1.052-1.649, P = .016). CONCLUSION: Increased intubation attempts were associated with increased incidence of severe IVH in infants with BW less than 750 g and in infants less than 1500 g who were intubated only in the delivery room. Prospective studies are needed to further evaluate the relationship between intubation attempts and severe IVH.

A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates.

BACKGROUND: Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown. METHODS: We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn. RESULTS: We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 µW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0°C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion. CONCLUSIONS: Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810.).

Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels.

Neuroimaging and neurodevelopmental outcome in extremely preterm infants.

BACKGROUND: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age. METHODS: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors. RESULTS: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes. CONCLUSIONS: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging.

Safety and efficacy of filtered sunlight in treatment of jaundice in African neonates.

OBJECTIVES: Evaluate safety and efficacy of filtered-sunlight phototherapy (FS-PT). METHODS: Term/late preterm infants #14 days old with clinically significant jaundice, assessed by total bilirubin (TB) levels, were recruited from a maternity hospital in Lagos, Nigeria. Sunlight was filtered with commercial window-tinting films that remove most UV and significant levels of infrared light and transmit effective levels of therapeutic blue light. After placing infants under an FS-PT canopy, hourly measurements of axillary temperatures, monitoring for sunburn, dehydration, and irradiances of filtered sunlight were performed. Treatment was deemed safe and efficacious if infants were able to stay in FS-PT for $5 hours and rate of rise of TB was ,0.2 mg/dL/h for infants #72 hours of age or TB decreased for infants .72 hours of age. RESULTS: A total of 227 infants received 258 days of FS-PT. No infant developed sunburn or dehydration. On 85 (33%) of 258 treatment days, infants were removed briefly from FS-PT due to minor temperature-related adverse events. No infant met study exit criteria. FS-PT was efficacious in 92% (181/197) of evaluable treatment days. Mean 6 SD TB change was ­0.06 6 0.19 mg/dL/h. The mean 6 SD (range) irradiance of FS-PT was 38 6 22 (2­115) mW/cm2/nm, measured by the BiliBlanket Meter II. CONCLUSIONS: With appropriate monitoring, filtered sunlight is a novel, practical, and inexpensive method of PT that potentially offers safe and efficacious treatment strategy for management of neonatal jaundice in tropical countries where conventional PT treatment is not available.

Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT).

OBJECTIVE: To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT), using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure (CPAP) vs intubation/surfactant. STUDY DESIGN: The Breathing Outcomes Study, a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age (CA). Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention. RESULTS: One or more interviews were completed for 918 of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and 31.0%, respectively, and did not differ between the study arms of either randomized intervention. Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity (except for croup and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs 36.5%; P<.05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%; P<.05), and physician or emergency room visits for breathing problems (68.0% vs 72.9%; P<.05) by 18-22 months CA. CONCLUSION: Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates.

Treatment of neonatal jaundice with filtered sunlight in Nigerian neonates: study protocol of a non-inferiority, randomized controlled trial.

BACKGROUND: Severe neonatal jaundice and its progression to kernicterus is a leading cause of death and disability among newborns in poorly-resourced countries, particularly in sub-Saharan Africa. The standard treatment for jaundice using conventional phototherapy (CPT) with electric artificial blue light sources is often hampered by the lack of (functional) CPT devices due either to financial constraints or erratic electrical power. In an attempt to make phototherapy (PT) more readily available for the treatment of pathologic jaundice in underserved tropical regions, we set out to test the hypothesis that filtered sunlight phototherapy (FS-PT), in which potentially harmful ultraviolet and infrared rays are appropriately screened, will be as efficacious as CPT. METHODS/DESIGN: This prospective, non-blinded randomized controlled non-inferiority trial seeks to enroll infants with elevated total serum/plasma bilirubin (TSB, defined as 3 mg/dl below the level recommended by the American Academy of Pediatrics for high-risk infants requiring PT) who will be randomly and equally assigned to receive FS-PT or CPT for a total of 616 days at an inner-city maternity hospital in Lagos, Nigeria. Two FS-PT canopies with pre-tested films will be used. One canopy with a film that transmits roughly 33% blue light (wavelength range: 400 to 520 nm) will be used during sunny periods of a day. Another canopy with a film that transmits about 79% blue light will be used during overcast periods of the day. The infants will be moved from one canopy to the other as needed during the day with the goal of keeping the blue light irradiance level above 8 µW/cm²/nm. PRIMARY OUTCOME: FS-PT will be as efficacious as CPT in reducing the rate of rise in bilirubin levels. Secondary outcome: The number of infants requiring exchange transfusion under FS-PT will not be more than those under CPT. CONCLUSION: This novel study offers the prospect of an effective treatment for infants at risk of severe neonatal jaundice and avoidable exchange transfusion in poorly-resourced settings without access to (reliable) CPT in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01434810.

Challenges in the practice of human milk nutrition in the neonatal intensive care unit.

The use of human milk for preterm infants has increased over the past decade reflecting an improved awareness of the benefits of human milk. Inherent in this paradigm shift is the recognition that human milk is a living tissue; full of immune cells, probiotics and hundreds of compounds that confer bioactivity and immune protective properties. Together these factors deliver a powerful effect in reducing clinical morbidities such as necrotizing enterocolitis and sepsis in the preterm infant. However, as breastfeeding is not possible for the very premature infant, human milk needs to be introduced in the neonatal intensive care unit through alternative means, resulting in significant handling and manipulation of maternal milk. This presents risks in quality control and provision of optimal nutrition delivery. Therefore, a comprehensive approach to standardizing preterm infant nutrition is essential to optimize the collection, storage, fortification and delivery of human milk to preterm neonates. In this paper we discuss the challenges presented by supporting human milk nutrition, and the rationale for the development of the Supporting Premature Infant Nutrition (SPIN) program at our institution.

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

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

Developmental scores at 1 year with increasing gestational age, 37-41 weeks.

OBJECTIVE: To examine the relationship between gestational age and mental and psychomotor development scores in healthy infants born between 37 and 41 weeks. METHODS: The cohort included 1562 participants enrolled during infancy in an iron deficiency anemia preventive trial in Santiago, Chile. All participants were healthy, full-term (37-41 weeks) infants who weighed 3 kg or more at birth. Development at 12 months was assessed using the Bayley Scales of Infant Development. Using generalized linear modeling, we analyzed the association between gestational age and 1-year-old developmental status, taking into account potential confounders including birth weight percentile, gender, socioeconomic status, the home environment, iron status, and iron supplementation. RESULTS: For each additional week of gestation, the Mental Development Index increased by 0.8 points (95% confidence interval = 0.2-1.4), and the Psychomotor Development Index increased by 1.4 points (95% confidence interval = 0.6-2.1) controlling for birth weight percentile, gender, socioeconomic status, and home environment. CONCLUSIONS: In a large sample of healthy full-term infants, developmental scores obtained using the Bayley Scales of Infant Development at 12 months increased with gestational age (37-41 weeks). There is increasing evidence that birth at 39 to 41 weeks provides developmental advantages compared with birth at 37 to 38 weeks. Because cesarean deliveries and early-term inductions have increased to 40% of all births, consideration of ongoing brain development during the full-term period is an important medical and policy issue.