Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor Respiratory Function at 7-8 Years of Age.

OBJECTIVE: To clarify the relationships of 3 definitions of severity of bronchopulmonary dysplasia (BPD) with adverse neurodevelopmental and respiratory outcomes at early school-age. STUDY DESIGN: Participants comprised 218 consecutive survivors to 7-8 years of age born either <28 weeks' gestation or weighing <1000 g in Victoria, Australia, in 2005. BPD was classified as none, grade 1 (mild), grade 2 (moderate), or grade 3 (severe), using 2 commonly accepted definitions: 1) Jobe2001, and 2) Higgins2018, and our own 3) Victorian Infant Collaborative Study (VICS) 2005, adapted from Jensen2019. Outcomes included major neurodevelopmental disability, low IQ and academic achievement, poor motor function, and poor respiratory function as assessed by spirometry. Outcomes for children with each grade of BPD were compared with children with no BPD. RESULTS: Of the 218 survivors, 132 (61%) had BPD on Jobe2001 criteria, and 113 (52%) had BPD on both Higgins2018 and VICS2005 criteria. Grade 1 on any criteria was not associated with any adverse neurodevelopmental outcomes. Grade 1 on both Higgins2018 and VICS2005 was associated with reduced spirometry, grade 2 on both Higgins2018 and VICS2005, and grade 3 on all criteria were associated with increased risk for both adverse neurodevelopmental and respiratory outcomes. CONCLUSIONS: Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes.

Neurodevelopment and physical measurements in infants with birthweight of 500 grams or less.

BACKGROUND: In infants born weighing ≤500 g, little has been studied about the association between neurodevelopmental prognosis and growth. This study aimed to evaluate the association between neurodevelopmental impairment (NDI) and z-scores of physical measurements in infants born weighing ≤500 g. METHODS: A single-center, retrospective cohort study in a level IV neonatal intensive care unit in Japan. Infants born weighing ≤500 g between 2010 and 2019 were eligible. Z-scores in weight, length/height, and head circumference at birth, due date (or discharge), 6 and 18 months of corrected age, and 3 years of age were compared between infants with and without NDI at 3 years of age. Three infants with severe intraventricular hemorrhage or periventricular leukomalacia were excluded from the comparison analyses. NDI was defined as having a developmental quotient of ≤70, cerebral palsy, visual impairment, or hearing impairment. RESULTS: Of 22 eligible infants, the incidence of NDI at 3 years of age was 54.5%. The z-score was significantly smaller in the NDI group (n = 10) than that in the non-NDI group (n = 9) in head circumference at birth (median, -1.94 vs. -0.75; Z = 0.54; p = 0.020), and in height at 18 months of corrected age (median, -2.84 vs. -1.79; Z = 0.58; p = 0.013) and 3 years of age (median, -2.02 vs. -1.21; Z = 0.47; p = 0.046). CONCLUSIONS: NDI at 3 years of age was associated with a small head circumference z-score at birth, height at 18 months of corrected age, and height at 3 years of age in infants born weighing ≤500 g.

Hemodynamic evaluation of extremely low birth weight infants during the first 7 days of life.

BACKGROUND AND AIM: We aimed to investigate the hemodynamic status of extremely low birth weight (ELBW) infants during the transitional period under intensive management. METHODS: This retrospective cohort study analyzed left ventricular ejection fraction (LVEF), left ventricular end-systolic wall stress (ESWS), left ventricular internal dimension in diastole (LVIDd), and mean arterial pressure (MAP) of ELBW infants during their first week of life. Small for gestational age (SGA), histological chorioamnionitis (hCAM), severe intraventricular hemorrhage (IVH), and non-survival to discharge infants were compared to their counterparts. RESULTS: Sixty-two infants (25.7 ± 2.1 weeks, 700.7 ± 165.4 g) were analyzed. MAP gradually increased. Median LVEF was 69.8 % on day 1, decreased to 62.7 % on day 2, then increased throughout the week. ESWS was lowest at birth, rose to 28.2 g/cm2 on day 2, and decreased on day 6. There were no significant changes in LVIDd. SGA infants had higher MAP throughout, higher LVEF on day 2 and 3, but lower LVEF on day 5 to 7. LVIDd was lower in hCAM group. Severe IVH group had a more significant drop in LVEF on day 2, higher ESWS, and a higher incidence of hemodynamic significant patent ductus arteriosus (hsPDA). Non-survival had lower LVIDd. CONCLUSIONS: MAP increased gradually. Hemodynamic instability was observed in the first two days, with decreased LVEF and increased ESWS before stabilization. We observed an alteration in hemodynamic adaptation in SGA and hCAM infants. Severe IVH group experienced early hemodynamic instability and a higher incidence of hsPDA.

Expiratory airflow at 7-8 years of age in children born extremely low birthweight from 14 years before to 14 years after the introduction of exogenous surfactant.

Background: It is unclear if expiratory airflow in survivors born extremely low birth weight (ELBW; 500-999 g) has improved after the introduction of exogenous surfactant into clinical practice in 1991. The primary aim of this study was to describe the changes in airflow at 7-8 years of age of survivors born ELBW in five discrete cohorts from 14 years before to 14 years after the introduction of exogenous surfactant into clinical practice. Methods: The cohorts comprised consecutive survivors born ELBW in 1977-82 and 1985-87 at the Royal Women's Hospital, Melbourne, and in 1991-92, 1997 and 2005 in the state of Victoria, Australia. Survival rates to 2-years of age for infants born ELBW in the state of Victoria rose from approximately 1-in-4 to 3-in-4 over the time of this study. Expiratory airflow measurements at 7-8 years included the forced expired volume in 1 s (FEV1), converted to z-scores for age, height, sex, and race. Findings: There were 596 ELBW participants with expiratory flow data, 280 (47%) of whom had bronchopulmonary dysplasia (BPD). Overall, there was little change in zFEV1 over the 28-year period (mean change per year; 0.003, 95% CI -0.010, 0.015, P = 0.67). There was, however, evidence of an interaction between BPD and year; zFEV1 in those who had BPD fell over time (mean change per year -0.019, 95% CI -0.037, -0.009, P = 0.035), whereas zFEV1 improved in those who did not have BPD (mean change per year 0.021, 95% CI 0.006, 0.037, P = 0.007). Interpretation: Contrary to recent evidence, expiratory airflow of children born ELBW has not improved with the introduction of surfactant, and may be deteriorating in those who had BPD. Funding: National Health and Medical Research Council (Australia); Victorian Government's Operational Infrastructure Support Program.

Outcomes of patent foramen ovale greater than 3 mm at birth in extremely low birthweight infants.

BACKGROUND: Foramen ovale (FO) is an obligate fetal shunt that typically resolves after birth, although patency throughout life is not uncommon. The natural history of patent FO (PFO) is known in term infants, but less is known about its course in extremely preterm infants. We describe the echocardiographic changes in FO size from birth to discharge in extremely low birth weight (ELBW) infants in this retrospective study. METHODS: Cohort was divided based on size of FO at birth. Size of FO at discharge was measured and evaluated relative to postnatal weight gain. Demographics and clinical outcomes were compared between the two groups. RESULTS: Of the 54 ELBW infants, 50 were born with FO less than 3 mm in diameter (small), and 4 were born with FO greater than 3 mm (large). Of small defects, the majority (44/50, 88%) did not increase in size with weight gain, and minority (6/50, 12%) increased in size, and three of these 6 patients, FO grew to be slightly larger than 3 mm. In contrast, all large defects (4 of 4, 100%) nearly doubled in size with postnatal growth. These 4 ELBW infants with enlargement of FO had a flap valve evident on echocardiogram obtained prior to discharge, and subsequently closed on outpatient follow-up echocardiograms, although time to resolution was variable (6 months - 3 years). One infant had presumptive resolution because of the presence of flap valve. CONCLUSION: No maternal or neonatal demographic characteristics were predictive of FO enlargement, although, demonstrable flap valve on discharge echocardiogram correlated with resolution of FO on outpatient follow-up echocardiogram. Therefore, based on our data, we recommend that ELBW infants born with large FO should have echocardiographic re-evaluation of the atrial septal opening prior to discharge, to specify the presence of a flap valve or lack thereof, which is an important detail that can help a neonatologist determine the need for outpatient cardiac follow-up.

Myocardial function including estimates of myocardial work in young adults born very preterm or with extremely low birthweight - a cohort study.

BACKGROUND: Preterm birth and low birthweight have been associated with increased risk of heart failure and cardiovascular disease in young adulthood. However, results from clinical studies of myocardial function are not consistent. Echocardiographic strain analyses allow detection of early stages of cardiac dysfunction, and non-invasive estimates of myocardial work can provide additional information on cardiac function. We aimed to evaluate left ventricular (LV) myocardial function including measures of myocardial work in young adults born very preterm (gestational age < 29 weeks) or with extremely low birthweight (< 1000 g) (PB/ELBW), compared with term-born age- and sex matched controls. METHODS: 63 PB/ELBW and 64 controls born in Norway in the periods 1982-1985, 1991-1992, and 1999-2000 were examined with echocardiography. LV ejection fraction (EF) and LV global longitudinal strain (GLS) were measured. Myocardial work was estimated from LV pressure-strain loops after determination of GLS and construction of a LV pressure curve. Diastolic function was evaluated by determination of the presence or absence of elevated LV filling pressure, including measures of left atrial longitudinal strain. RESULTS: The PB/ELBW with mean birthweight 945 (standard deviation (SD) 217) grams, mean gestational age 27 (SD 2) weeks, and mean age 27 (SD 6) years had LV systolic function mainly within normal range. Only 6% had EF < 50% or impaired GLS >-16%, but 22% had borderline impaired GLS between - 16% and - 18%. Mean GLS in PB/ELBW (-19.4% (95% confidence interval (CI) -20.0, -18.9)) was impaired compared to controls (-20.6% (95% CI -21.1, -20.1)), p = 0.003. Lower birthweight was associated to more impaired GLS (Pearson correlation coefficient - 0.2). Means of EF, measures of diastolic function including left atrial reservoir strain, global constructive and wasted work, global work index and global work efficiency was similar in PB/ELBW and controls. CONCLUSION: The young adults born very preterm or with extremely low birthweight had impaired LV-GLS compared to controls, although systolic function mainly within normal range. Lower birthweight was associated with more impaired LV-GLS. These findings could indicate an elevated lifetime risk of developing heart failure in preterm born individuals. Measures of diastolic function and myocardial work were similar compared to controls.

Effects of a small-baby protocol on early and long-term outcomes in extremely preterm infants: A quality improvement study.

BACKGROUND: Extremely preterm (EPT) infants (≤28 weeks) remain at risk for poor outcomes. Small baby protocols (SBPs) may improve outcomes, but optimal strategies are unknown. METHODS: This study evaluated whether EPT infants managed using an SBP would have better outcomes compared to a historical control (HC) group. The study compared a HC group of EPT infants 23 0/7 weeks to 28 0/7 weeks GA (2006-2007), to a similar SBP group (2007-2008). Survivors were followed until 13 years of life. The SBP emphasized antenatal steroids, delayed cord clamping, respiratory and hemodynamic minimalism, prophylactic indomethacin, early empiric caffeine, and control of sound and light. RESULTS: There were 35 HC subjects and 35 SBP subjects. The SBP group had less severe IVH-PVH (9 % vs. 40 %, risk ratio 0.7, 95 % CI 0.5-0.9, P = 0.002) mortality (17 % vs. 46 %, risk ratio 0.6, 95 % CI 0.5-0.9, P = 0.004), and acute pulmonary hemorrhage (6 % vs. 23 %, risk ratio 0.8, 95 % CI 0.7-1.0, P = 0.04). Compliance with the SBP protocol was excellent. For the SBP group in the first 72 h, no subjects received inotropes, hydrocortisone, or sodium bicarbonate. Intubation, mechanical ventilation, fluid boluses, sedation, red blood cell transfusions, and insulin use decreased. At 10-13 years, more SBP subjects had survived without NDI (51 % vs. 23 %, risk ratio = 1.6, 95 % CI = 1.1-2.4, P = 0.01). More SBP subjects also survived without NDI and with a Vineland Adaptive Behavior Composite score > 85 (44 % vs. 11 %, risk ratio = 2.0, 95 % CI = 1.2-3.2, P ≤0.001). The SBP group had less visual impairment. CONCLUSION: An SBP was associated with improved outcomes, including normal neurologic survival after 10 years.

Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

Intellectual functioning in survivors of extremely low birthweight: Cognitive outcomes in childhood and adolescence.

BACKGROUND: Infants born at extremely low birthweight (ELBW: ≤1000 g) are vulnerable to intellectual disabilities, but the factors that may distinguish between ELBW survivors with and without these impairments are not well understood. In this study, prospective associations between neonatal factors and functional outcomes in childhood and adolescence were compared in ELBW survivors with and without borderline intellectual functioning (BIF). METHODS: Borderline intellectual functioning was defined by IQ < 85, assessed at 8 years. Among 146 ELBW survivors, 48 (33%) had IQ scores under 85, and 98 (67%) had scores equal to or over 85. Group differences in demographic and risk factors were assessed via t-test, chi-squared analysis or non-parametric tests. Neonatal factors that differed between ELBW groups were tested for association with adaptive behaviour assessed at age 5 years, and reading and arithmetic skills assessed at ages 8 and 15 years, using hierarchical regression models. RESULTS: Extremely low birthweight survivors with BIF had significantly lower birthweights than ELBW survivors without BIF (790 vs. 855 g, P < 0.01) and were more likely to be born to mothers with lower socioeconomic status (SES) (78% vs. 48%, P < 0.01). These ELBW survivors also were more likely to be diagnosed with significant neurosensory impairment (NSI; 35% vs. 19%, P < 0.04), experienced more bronchopulmonary dysplasia (56% vs. 38%, P < 0.04), received more days of respiratory support (median 33 vs. 14 days, P < 0.01) and remained in hospital for longer periods (median 81 vs. 63 days, P < 0.03). Birthweight, familial SES, NSI and duration of respiratory support were significant predictors for one or more outcomes. Across groups, lower familial SES was associated with lower academic scores (Ps < 0.05), and NSI predicted lower adaptive functioning (Ps < 0.001). Other associations were moderated by group: among ELBW survivors with BIF, heavier birthweights predicted better arithmetic skills, the presence of NSI was associated with poorer arithmetic skills and more ventilation days predicted poorer reading skills. CONCLUSIONS: At birth, ELBW survivors with BIF faced more physiological and social disadvantages and required more medical intervention than their ELBW peers without BIF. Smaller birth size, NSI burden and prolonged neonatal ventilatory support displayed gradients of risk for childhood and adolescent academic outcomes across groups. Whereas academic performance in ELBW survivors with BIF was sensitive to variation in birth size, NSI or ventilation days, ELBW survivors without BIF attained thresholds of intellectual ability that were sufficient to support higher levels of academic performance at both ages, regardless of their status on these factors. The findings are discussed in relation to Zigler's developmental theory of intellectual disability.

Dexamethasone may affect the occurrence of parenteral nutrition-associated cholestasis in preterm neonates.

Introduction: Glucocorticoids are currently used for the co-therapeutic management of autoimmune hepatitis and some cholestatic diseases. Thus far, we do not know the efficacy of glucocorticoids in the treatment of parenteral nutrition-associated cholestasis. We aimed to analyze whether the administration of late postnatal dexamethasone for treating bronchopulmonary dysplasia influence the occurrence of parenteral nutrition-associated cholestasis in preterm neonates. Methods: A retrospective study was conducted for 78 preterm neonates without major anomalies (gestational age was <30 weeks, and birthweight was ≤1000 g) hospitalized in a neonatal unit. Total and direct serum bilirubin levels were measured about every two weeks for all neonates. Data including the administration of dexamethasone, intravenous nutrition, and enteral feeding were collected by at least three audits. Results: A total of 15 preterm neonates were diagnosed with parenteral nutrition-associated cholestasis, and after stopping parenteral nutrition, the direct bilirubin value decreased to the normal level for no longer than 150 days. The prolonged duration of parenteral nutrition was a risk factor, and late postnatal dexamethasone treatment was a protective factor in reducing the incidence of parenteral nutrition-associated cholestasis. Conclusion: Dexamethasone treatment may reduce the occurrence of parenteral nutrition-associated cholestasis in preterm neonates.

Less-Invasive Diagnostic Approaches for Infants with Suspected Differences of Sex Development: A Case Report of a 297-g Neonate with Ambiguous Genitalia.

Less-invasive diagnostic approaches for low-birthweight preterm neonates with suspected differences of sex development have not been established. Herein, we describe our diagnostic approaches for a 297-g neonate with ambiguous genitalia. Using a fiberscope, the external genitalia were inspected in an incubator to minimize the risk of hypothermia and infection. Endotracheal aspirate, collected during routine care, was used for genetic testing to avoid anemia and vital signs fluctuations caused by peripheral blood sampling. Array comparative genomic hybridization indicated a 46,XY karyotype. No pathogenic variants of AR and SRD5A2 were found. Endocrinological data could not be evaluated owing to the absence of reference data. Identification and structural evaluation of the internal genitalia and gonads were difficult. On postnatal day 42, the parents assigned their baby's sex as male. Our less-invasive diagnostic approaches of inspection and genetic testing are useful for management, including sex assignment in extremely low-birthweight preterm neonates with ambiguous genitalia.

The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants.

BACKGROUND: Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants. METHODS: The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity. DISCUSSION: The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery. TRIAL REGISTRATION: Trial registration data: June 25, 2019  NCT03997266 .

Trends in survival, perinatal morbidities and two-year neurodevelopmental outcomes in extremely low-birthweight infants over four decades.

BACKGROUND: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. OBJECTIVE: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. METHODS: Analysis of data from discrete population-based prospective cohort studies of all live births free of lethal anomalies with birthweight 500-999 g in the state of Victoria, Australia, over 6 eras: 1979-80, 1985-87, 1991-92, 1997, 2005 and 2016-17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two-year neurodevelopmental outcomes. RESULTS: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979-80, 70%; 2016-17, 84%), and more were offered active care (1979-80, 58%; 2016-17, 90%). Survival to 2 years rose substantially, from 25% in 1979-80 to 80% in 2016-17. In survivors, rates of any assisted ventilation rose from 75% in 1979-80 to 99% in 2016-17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two-year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979-80 to 30 in 2016-17, but annual numbers free of major disability increased much more, from 31 in 1979-80 to 147 in 2016-17. CONCLUSIONS: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability.

Evaluation of postoperative complications for patent ductus arteriosus in extremely-low-birthweight infants.

BACKGROUND: Patent ductus arteriosus (PDA), which disrupts the hemodynamics early after birth, causes intraventricular hemorrhage and neonatal necrotizing. Unlike medical treatment for hemodynamically significant PDA, there are institutional disparities in the criteria for surgical treatment METHODS: We aimed to clarify the postoperative indications of surgery for hemodynamically significant PDA and the postoperative complications associated with surgery. RESULTS: Thirty-six extremely-low-birthweight infants (median gestational age 25.2 weeks, median birthweight 699 g) required video-assisted thoracoscopic surgery for PDA (VATS-PDA). The treatment indication of VATS-PDA was resistance to medical treatment in 17 cases, relapsed PDA in 15 cases, and no additional administration of indomethacin because of severe side effects in four cases. Complications with VATS-PDA occurred in eight of 36 cases. There were three cases of pneumothorax, two of thoracotomy transition, two of pulmonary hemorrhage, and four of post-ligation cardiac syndrome (PLCS). VATS-PDA-related death occurred in two cases due to PLCS. The frequency of four or more administrations of indomethacin, with or without postoperative complications, was 88% vs. 39%, respectively (P = 0.04). CONCLUSIONS: All postoperative deaths were caused by PLCS, which had the highest risk of poor prognosis. VATS-PDA should be considered for unclosed PDA after one course of indomethacin administration.

The causal effect of being born extremely preterm or extremely low birthweight on neurodevelopment and social-emotional development at 2 years.

AIM: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social-emotional development at 2 years' corrected age. METHODS: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term-born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development-3rd edition and the Infant-Toddler Social and Emotional Assessment. Delay was defined as <-1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. RESULTS: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social-emotional competence (4.1 [1.6, 10.2]). CONCLUSION: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social-emotional competence at 2 years' corrected age. Close developmental surveillance, including social-emotional development, is recommended.

Case Report: Treatment of Extremely Preterm Infants With Birthweight Below 300 g: Case Series.

Reports on the birth of infants weighing <300 g are quite rare and little is known about the best practices in treating such micropreemies. Therefore, we report here on three cases of low birthweight infants weighing <300 g, of whom two infants survived. The birthweights and gestational ages were ranging 279-293 g and 22 + 6/7 - 23 + 6/7 weeks, respectively. All the infants had severe fetal growth restriction and prematurity. The infant in case 1 died of hepatic rupture, perhaps due to birth trauma, which emphasized the need for less invasive obstetric procedures including en caul delivery. The infant in case 2 managed to survive through severe prematurity secondary to hydrops fetalis. However, complications followed soon as tracheal granulation tissue was formed with neurodevelopmental impairment. The infant in case 3 was born recently and her clinical course was less remarkable without severe complications, despite having the least gestational age and birthweight among the three patients. The improved care protocols for extremely low birthweight infants over these years through experiential learning including that with cases 1 and 2 may have ensured the better outcome of case 3. Accumulating evidence and recording the experience of such cases with continuous constructive discussion can contribute to better outcomes and appropriate parental counseling for extremely small babies in the future.