Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

The role of fetal hemoglobin in the artificial placenta: A premature ovine model.

INTRODUCTION: A radical paradigm shift in the treatment of premature infants failing conventional treatment is to recreate fetal physiology using an extracorporeal Artificial Placenta (AP). The aim of this study is to evaluate the effects of changing fetal hemoglobin percent (HbF%) on physiology and circuit function during AP support in an ovine model. METHODS: Extremely premature lambs (n = 5) were delivered by cesarean section at 117-121 d estimated gestational age (EGA) (term = 145d), weighing 2.5 ± 0.35 kg. Lambs were cannulated using 10-14Fr cannulae for drainage via the right jugular vein and reinfusion via the umbilical vein. Lambs were intubated and lungs were filled with perfluorodecalin to a meniscus with a pressure of 5-8 cm H2O. The first option for transfusion was fetal whole blood from twins followed by maternal red blood cells. Arterial blood gases were used to titrate AP support to maintain fetal blood gas values. RESULTS: The mean survival time on circuit was 119.6 ± 39.5 h. Hemodynamic parameters and lactate were stable throughout. As more adult blood transfusions were given to maintain hemoglobin at 10 mg/dL, the HbF% declined, reaching 40% by post operative day 7. The HbF% was inversely proportional to flow rates as higher flows were required to maintain adequate oxygen saturation and perfusion. CONCLUSIONS: Transfusion of adult blood led to decreased fetal hemoglobin concentration during AP support. The HbF% was inversely proportional to flow rates. Future directions include strategies to decrease the priming volume and establishing a fetal blood bank to have blood rich in HbF.

Prediction scores based on neonatal inflammatory markers for chorioamnionitis and funisitis in extremely low gestational age neonates.

AIM: The aim of the study was to examine the predictive value of inflammatory markers for chorioamnionitis and funisitis in extremely low gestational age neonates. METHODS: According to the Redline histopathological classification, extremely low gestational age neonates were classified into: (1) maternal inflammatory response ≤1 or ≥2, based on inflammatory findings of the placenta and (2) foetal inflammatory response ≤1 or ≥2, based on inflammatory findings of the umbilical cord. On admission and 12-36 h postnatally, procalcitonin and high-sensitivity C-reactive protein levels and white blood cell and neutrophil counts were compared. For both maternal and foetal inflammatory responses ≥2, the predictive value of each inflammatory marker was calculated. RESULTS: On admission, procalcitonin had the best predictive value for maternal and foetal inflammatory response ≥2. The maternal inflammatory response ≥2 prediction score includes procalcitonin level on admission, high-sensitivity C-reactive protein level and white blood cell count at 12-36 h postnatally. Foetal inflammatory response ≥2 prediction score includes procalcitonin level and white blood cell count on admission and 12-36 h postnatally. The sensitivities were 96.4% and 96.3%, respectively. CONCLUSION: Procalcitonin, high-sensitivity C-reactive protein levels and white blood cell count provide highly sensitive prediction scores for chorioamnionitis and funisitis in extremely low gestational age neonates.

Physiological aspects of cardiopulmonary dysanapsis on exercise in adults born preterm.

Progressive improvements in perinatal care and respiratory management of preterm infants have resulted in increased survival of newborns of extremely low gestational age over the past few decades. However, the incidence of bronchopulmonary dysplasia, the chronic lung disease after preterm birth, has not changed. Studies of the long-term follow-up of adults born preterm have shown persistent abnormalities of respiratory, cardiovascular and cardiopulmonary function, possibly leading to a lower exercise capacity. The underlying causes of these abnormalities are incompletely known, but we hypothesize that dysanapsis, i.e. discordant growth and development, in the respiratory and cardiovascular systems is a central structural feature that leads to a lower exercise capacity in young adults born preterm than those born at term. We discuss how the hypothesized system dysanapsis underscores the observed respiratory, cardiovascular and cardiopulmonary limitations. Specifically, adults born preterm have: (1) normal lung volumes but smaller airways, which causes expiratory airflow limitation and abnormal respiratory mechanics but without impacts on pulmonary gas exchange efficiency; (2) normal total cardiac size but smaller cardiac chambers; and (3) in some cases, evidence of pulmonary hypertension, particularly during exercise, suggesting a reduced pulmonary vascular capacity despite reduced cardiac output. We speculate that these underlying developmental abnormalities may accelerate the normal age-associated decline in exercise capacity, via an accelerated decline in respiratory, cardiovascular and cardiopulmonary function. Finally, we suggest areas of future research, especially the need for longitudinal and interventional studies from infancy into adulthood to better understand how preterm birth alters exercise capacity across the lifespan.

Incidence and risk factors for retinopathy of prematurity in premature, extremely low birth weight and extremely low gestational age infants.

BACKGROUND: The aim of the study was to determine the incidence and risk factors of retinopathy of prematurity (ROP) in premature, extremely low birth weight (BW, ELBW) and extremely low gestational age (GA, ELGA) infants. METHODS: The medical records of preterm infants who were screened for ROP between January 2012 and December 2020 were retrospectively reviewed. Only one eye of each infant with higher grade ROP was included in the study. BW; GA; medical characteristics; the presence, severity, and need for treatment of ROP were recorded. Infants were divided into groups according to BW (≤1000 g, 1001-1750 g, > 1750 g) and GA (≤25w, 26-28w, 29-31w, 32-34w, ≥35w) and data were analyzed. RESULTS: Data of 2186 infants were evaluated. The overall incidences of any stage ROP and ROP requiring treatment were 43.5 and 8.0%, respectively. These rates were 81.1 and 23.9% in ELBW (≤1000 g) infants and were 92.9 and 64.3% in ELGA (≤25w) infants, respectively. The rates of ROP, the median duration of oxygen therapy and systemic diseases increased significantly as BW and GA decreased. The median duration of oxygen therapy and the rates of sepsis, pulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH) were statistically higher in infants with ROP compared to those without ROP (p < 0.001). Multivariate regression analysis demonstrated that low BW and GA; prolonged duration of oxygen therapy; presence of PDA and necrotizing enterocolitis (NEC) were important risk factors for ROP. CONCLUSIONS: ELBW and ELGA infants develop higher rates of ROP and severe ROP. Prolonged duration of oxygen therapy, the presence of concomitant neonatal sepsis, BPD, IVH, PDA, and NEC further increases the risk of ROP.

Amino acid infusions in umbilical artery catheters enhance protein administration in infants born at extremely low gestational age.

AIM: It is challenging to provide extremely low gestational age neonates (ELGANs) with adequate protein supply. This study aimed to investigate whether amino acid (AA) infusion in the umbilical artery catheter (UAC) in ELGANs is safe and enhances protein supply and growth. METHOD: A before and after study including infants born <27 weeks, treated in Uppsala, Sweden, during 2004-2007, compared those receiving normal saline/10% dextrose in water with those receiving AA infusion in the UAC. Data were retrieved from the Extremely Preterm Infants in Sweden Study, hospital records and the Swedish Neonatal Quality Register. Group comparisons, univariate and multivariate analyses were conducted. RESULTS: AA group (n = 41, females 39%) received on average approximately 0.3 g/kg/day more protein during the first postnatal week, compared to control group (n = 30, females 40%) (unstandardised coefficient (B) 0.26, p .001) but no difference was noted during 8-28 postnatal days. The type of infusion was not associated with growth variables. The incidence of neonatal morbidities and UAC-related thrombosis did not differ between the groups. CONCLUSION: AA infusions in the UACs in ELGANs is safe and enhances protein supply during the first postnatal week. However, this practice is not associated with growth during the first 28 postnatal days.

Antenatal and neonatal risk factors in very preterm children were associated with language difficulties at 9 years of age.

AIM: This Finnish study compared language and reading abilities between schoolchildren born at a very low gestational age (VLGA) of <32 weeks and at term and analysed any associations between antenatal and neonatal risk factors and language skills in the VLGA group. METHODS: We prospectively followed 76 children born at a VLGA and 50 children born at term when they reached a mean age of 9.0 (8.1-10.0) years. They attended mainstream schools and had no severe neurosensory disabilities. Receptive language ability, rapid naming and word reading were evaluated using standardised tests. RESULTS: Children in the VLGA group had lower scores for receptive language abilities (median 55.0 vs. 57.0, p = 0.01) and word reading (mean 4.4 vs. 5.1, p = 0.03) than the children in the term group. In the VLGA group, foetal growth restriction was associated with lower scores for rapid naming, early intraventricular haemorrhage was associated with poor word reading and respiratory distress syndrome was associated with poor rapid naming (p < 0.05). CONCLUSION: Schoolchildren born at a VLGA had more difficulties with receptive language abilities and word reading than children born at term. Foetal growth restriction and early neonatal morbidities were associated with language difficulties.

Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial.

OBJECTIVES: To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN: This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS: In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. CONCLUSIONS: A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01378273.

Physiology of Low Blood Pressure During the First Day After Birth Among Extremely Preterm Neonates.

OBJECTIVE: To investigate the circulatory physiology of hypotension during the first day after birth among stable extremely preterm neonates. STUDY DESIGN: Case-control study of neonates born at ≤276/7 weeks gestational age with hypotension, defined as mean blood pressure in mmHg less than gestational age in weeks for at least 1 hour during the first 24 hours after birth, who underwent comprehensive echocardiography assessment before commencement of cardiovascular drugs. Neonates with hypotension (n = 14) were matched by gestational age and intensity of respiratory support with normotensive neonates (n = 27) who underwent serial echocardiography during the first day after birth, and relatively contemporaneous echocardiography assessments were used for comparison. RESULTS: Neonates with hypotension had a higher frequency of patent ductus arteriosus ≥1.5 mm (71% vs 15%; P < .001) and ductal size (median diameter, 1.6 mm [IQR, 1.4-2.1] vs 1.0 mm [IQR, 0-1.3]; P = .002), higher echocardiography indices of left ventricular systolic function (mean shortening fraction, 34 ± 7% vs 26 ± 4%; P < .001; mean longitudinal strain, -16 ± 5% vs -14 ± 3%; P = .04; and mean velocity of circumferential fiber shortening, 1.24 ± 0.35 circ/s vs 1.01 ± 0.28 circ/s; P = .03), lower estimates of left ventricular afterload (mean end-systolic wall stress, 20 ± 7 g/cm2 vs 30 ± 9 g/cm2; P < .001 and mean arterial elastance, 43 ± 19 mmHg/mL vs 60 ± 22 mmHg/mL; P = .01), without significant difference in stress-velocity index z-score (-0.42 ± 1.60 vs -0.88 ± 1.30; P = .33). Neonates with hypotension had higher rates of any degree of intraventricular hemorrhage (71% vs 22%; P = .006). CONCLUSIONS: Low blood pressure in otherwise well extremely low gestational age neonates was associated with low systemic afterload and larger patent ductus arteriosus, but not left ventricular dysfunction.

Children born before 32 weeks of gestation displayed impaired reading fluency, comprehension and spelling skills at 9 years of age.

AIM: Our aim was to study whether prematurity, associated with prenatal and neonatal risk factors, affects specific literacy skills among school children born at a very low gestational age (VLGA) of <32 weeks. METHODS: The study group comprised 76 prospectively followed VLGA children born between November 1998 and November 2002 at Oulu University Hospital, Finland, and 51 term controls. The median gestational age of the VLGA children was 29.0 (24.1-31.9) weeks. All children were examined at a median age of 8.9 (8.0-9.9) years in Oulu between November 2007 and November 2011. Reading fluency, comprehension and spelling skills were evaluated using standardised tests for Finnish-speaking children. RESULTS: Very low gestational age children had significantly poorer test results in reading comprehension (median 6.9 vs 8.3, P = .014) and spelling (median 35.7 vs 38.0, P = .013) than term children. Furthermore, VLGA children more often performed below the 10th percentile normal values in spelling (P = .012) compared with term controls. Foetal growth restriction was associated with lower scoring in reading fluency (P = .023) and spelling (P = .004) among VLGA children. CONCLUSION: Very low gestational age school children performed poorer in reading comprehension and spelling than term children. In addition, poor foetal growth in VLGA children was associated with literacy problems.

Extremely low gestational age infants: Developing a multidisciplinary care bundle.

BACKGROUND: Clinical experience in managing extremely low gestational age infants, particularly those born <24 weeks' gestation, is limited in Canada. Our goal was to develop a bedside care bundle for infants born <26 weeks' gestation, with special considerations for infants of <24 weeks, to harmonize and improve quality of care. METHODS: We created a multidisciplinary working group with experience in caring for preterm infants, searched the literature from 2000 to 2019 to identify best practices for the care of extremely preterm infants and consulted colleagues across Canada and internationally. Iterative improvements were made following the Plan-Do-Study-Act methodology. RESULTS: A care bundle, created in October 2015, was divided into three time periods: initial resuscitation/stabilization, the first 72 hours and days 4 to 7, with each period subdivided in 8 to 12 care themes. Revisions and practice changes were implemented to improve skin integrity, admission temperature, timing of initiation of feeds, reliability of transcutaneous CO2 monitoring and ventilation. Of 127 infants <26 weeks admitted between implementation and end of 2019, 78 survived to discharge (61%). CONCLUSION: It will be important to determine, with ongoing auditing and further evaluation, whether our care bundle led to improvements of short- and long-term outcomes in this population. Our experience may be useful to others caring for extremely low gestational age infants.

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Infants of Extremely Low Gestational Age.

OBJECTIVE: To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation. STUDY DESIGN: Observational study of infants born April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley Scales of Infant and Toddler Development, 3rd edition, cognitive or motor score <70, blindness, or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education, and parenchymal hemorrhage. RESULTS: Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119 of 815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation, and normal head ultrasound, respectively; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs no intervention (80% vs 65%; aOR 2.2 [1.38-3.8]). Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex, and surgery for retinopathy; odds decreased with each additional gestational week. CONCLUSIONS: PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.

High Prevalence of Iron Deficiency Despite Standardized High-Dose Iron Supplementation During Recombinant Erythropoietin Therapy in Extremely Low Gestational Age Newborns.

OBJECTIVE: To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs). STUDY DESIGN: Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared. RESULTS: The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05). CONCLUSIONS: In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Predictors of Early Extubation after Patent Ductus Arteriosus Ligation among Infants Born Extremely Preterm Dependent on Mechanical Ventilation.

We conducted a retrospective study of 166 ventilator-dependent neonates born extremely preterm in whom patent ductus arteriosus was surgically ligated and evaluated the association of preoperative characteristics and time-to-successful postoperative extubation. Larger patent ductus arteriosus diameter ([>2.5 mm], adjusted hazard ratio 0.51, 95% CI 0.36-0.72) and left-ventricular dilatation (z score ≥2, adjusted hazard ratio 0.61, 95% CI 0.42-0.87) were associated with earlier extubation.

Sustained quality improvement in outcomes of preterm neonates with a gestational age less than 29 weeks: results from the Evidence-based Practice for Improving Quality Phase 3 1.

Quality improvement initiatives in neonatology have yielded positive results; however, few programs have demonstrated sustainability. We evaluated an ongoing, national quality improvement initiative (Evidence-based Practice for Improving Quality Phase 3 (EPIQ-3)) on outcomes of preterm neonates with a gestational age (GA) of 220-286 weeks (i.e., from 22 weeks and 0 days of gestation to 28 weeks and 6 days of gestation). Data from 7459 neonates admitted to 25 Canadian centers between 2013 and 2017 were studied. Trends in mortality and major morbidities were evaluated. The number of neonates with a GA of 220-236 weeks increased from 90 in 2013 to 139 in 2017 without a significant change in any other GA categories. In the entire cohort, the odds of composite outcome of mortality or any major morbidity (adjusted odds ratio (AOR) 0.72, 95% confidence interval (CI) 0.61-0.84) and of necrotizing enterocolitis (AOR 0.66, 95% CI 0.49-0.89) were lower in 2017 than in 2013. When calculated per year, the odds of composite outcome (AOR 0.93, 95% CI 0.89-0.97) and odds of necrotizing enterocolitis (AOR 0.89, 95% CI 0.82-0.96) decreased significantly. Among the subgroup of neonates with a GA of 260-286 weeks, the odds of composite outcome (AOR 0.63, 95% CI 0.51-0.79), necrotizing enterocolitis (AOR 0.44, 95% CI 0.26-0.73), and nosocomial infection (AOR 0.64, 95% CI 0.49-0.84) were reduced. The collaborative, multidisciplinary, nationwide EPIQ-3 program improved outcomes of preterm neonates, and the improvement was sustainable over 5 years.

Assessing Positive Child Health among Individuals Born Extremely Preterm.

OBJECTIVE: To assess the development of a Positive Child Health Index (PCHI) based on 11 adverse outcomes and evaluate the association of PCHI with quality of life (QoL) scores in a preterm cohort. STUDY DESIGN: A total of 889 children enrolled in the Extremely Low Gestational Age Newborn (ELGAN) study in 2002-2004 were followed up at 10 years of age. A parent/caregiver completed questionnaires for child QoL, asthma, visual or hearing impairment, gross motor function impairment, epilepsy, attention deficit/hyperactivity disorder, anxiety, and depression. The child was assessed for cognitive impairment, autism, and obesity. PCHI scores were computed and linear regression models were used to evaluate the relationship between QoL categories (psychosocial, physical, emotional, social, school, and total) and the PCHI (dichotomized and coded as a multilevel categorical predictor) and to assess sex differences. RESULTS: Among ELGAN children, higher PCHI scores were associated with higher reported QoL scores for all QoL categories. Children with no disorders and a PCHI of 100% had Pediatric Quality of Life Inventory total scores that were 11 points higher than children with 1 or more adverse outcomes (PCHI of <100%). Boys had lower QoL scores for the total, psychosocial, social, and school categories. CONCLUSIONS: Positive child health assessed using a quantitative PCHI was associated with QoL across the ELGAN cohort at school age. In the current study, the PCHI encompassed 11 outcomes assessed in ELGANs. Future research could include an enhanced panel of child health outcomes to support the use of PCHI as an indicator of positive child health.

Role of Genetic Susceptibility in the Development of Bronchopulmonary Dysplasia.

OBJECTIVE: To assess heritable contributions to bronchopulmonary dysplasia (BPD) risk in a twin cohort restricted to gestational age at birth <29 weeks. STUDY DESIGN: A total of 250 twin pairs (192 dichorionic, 58 monochorionic) born <29 weeks gestational age with known BPD status were identified. Three statistical methods applicable to twin cohorts (χ2 test, intraclass correlations [ICCs], and ACE modeling [additive genetic or A, common environmental or C, and unique environmental or E components]) were applied. Heritability was estimated as percent variability from A. Identical methods were applied to a subcohort defined by zygosity and to an independent validation cohort. RESULTS: χ2 analyses comparing whether neither, 1, or both of monochorionic (23, 19, 16) and dichorionic (88, 56, 48) twin pairs developed BPD revealed no difference. Although there was similarity in BPD outcome within both monochorionic and dichorionic twin pairs by ICC (monochorionic ICC = 0.34, 95% CI [0.08, 0.55]; dichorionic ICC = 0.39, 95% CI [0.25, 0.51]), monochorionic twins were not more likely than dichorionic twins to have the same outcome (P = .70). ACE modeling revealed no contribution of heritability to BPD risk (% A = 0.0%, 95% CI [0.0%, 43.1%]). Validation and zygosity based cohort results were similar. CONCLUSIONS: Our analysis suggests that heritability is not a major contributor to BPD risk in preterm infants <29 weeks gestational age.

Statewide Initiative to Reduce Postnatal Growth Restriction among Infants <31 Weeks of Gestation.

OBJECTIVE: To decrease the incidence of postnatal growth restriction, defined as discharge weight <10th percentile for postmenstrual age, among preterm infants cared for in New York State Regional Perinatal Centers. STUDY DESIGN: The quality improvement cohort consisted of infants <31 weeks of gestation admitted to a New York State Regional Perinatal Center within 48 hours of birth who survived to hospital discharge. Using quality improvement principles from the Institute for Healthcare Improvement and experience derived from successfully reducing central line-associated blood stream infections statewide, the New York State Perinatal Quality Collaborative sought to improve neonatal growth by adopting better nutritional practices identified through literature review and collaborative learning. New York State Regional Perinatal Center neonatologists were surveyed to characterize practice changes during the project. The primary outcome-the incidence of postnatal growth restriction-was compared across the study period from baseline (2010) to the final (2013) years of the project. Secondary outcomes included differences in z-score between birth and discharge weights and head circumferences. RESULTS: We achieved a 19% reduction, from 32.6% to 26.3%, in postnatal growth restriction before hospital discharge. Reductions in the difference in z-score between birth and discharge weights were significant, and differences in z-score between birth and discharge head circumference approached significance. In survey data, regional perinatal center neonatologists targeted change in initiation of feedings, earlier breast milk fortification, and evaluation of feeding tolerance. CONCLUSIONS: Statewide collaborative quality improvement can achieve significant improvement in neonatal growth outcomes that, in other studies, have been associated with improved neurodevelopment in later infancy.

The Youngest Survivor with Gestational Age of 215/7 Weeks.

The decision whether or not to resuscitate extremely low gestational age (GA) infants is recommended to be individualized according to antenatal counseling with parents, neonatologists, and obstetricians. A GA of 22°/7-236/7 weeks is generally considered as the lower end of the range where infants can be candidates for selective resuscitation. Below this lower end of periviable gestation, resuscitation is usually not considered and survivors are rarely reported. To date, the youngest survivor is an infant with a GA of 216/7 weeks reported in the English medical literature. Here, we report the case of a female infant, the first twin conceived through in vitro fertilization, with a GA of 215/7 weeks, who was resuscitated initially according to strong parental wishes after antenatal counseling and is still surviving at 43 months of age with fairly good neurodevelopmental outcome.