Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US.

Importance: High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives. Objective: To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants. Design, Setting, and Participants: This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children's hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded. Exposure: Any opioid exposure and methadone treatment. Main Outcomes and Measures: Regional and institutional variations in opioid exposure. Results: Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital. Conclusions and Relevance: In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

Total Hydrocortisone Dosage in the Neonatal Period May Be Related to Low Developmental Quotient in Extremely Low Birth Weight Infants: A Retrospective Cohort Study.

INTRODUCTION: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. METHODS: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. RESULTS: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.65, 95% CI: -3.73, -1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.66, 95% CI: -3.89, -1.42). CONCLUSION: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

Does faster weight trajectory lead to improved neurodevelopmental outcomes in ELBW infants with bronchopulmonary dysplasia?

OBJECTIVE: Examine the relationship between weight trajectory and 2-year neurodevelopmental outcomes for extremely low birthweight (ELBW) infants with BPD. STUDY DESIGN: Secondary analysis of infants born from 2010 to 2019. The predictor was BPD severity and the outcome was neurodevelopmental impairment, defined as any Bayley Scales of Infant Development (BSID) III score <70 at 24 months' corrected age. Repeated measures logistic regression was performed. RESULTS: In total, 5042 infants were included. Faster weight trajectory was significantly associated with a decreased probability of having at least one BSID III score <70 for infants with grade 1-2 BPD (p < 0.0001) and an increased probability of at least one BSID III score <70 for infants with grade 3 BPD (p < 0.009). There was no significant association between weight trajectory and BSID III score <70 for infants with grade 0 BPD. CONCLUSION: The association between postnatal weight trajectory and neurodevelopmental outcome in this study differs by BPD severity.

Transition to Adulthood for Extremely Preterm Survivors.

OBJECTIVE: To compare transition into adulthood of survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) in the postsurfactant era with term-born controls. METHODS: Prospective longitudinal cohort study of all EP/ELBW survivors born in the State of Victoria, Australia between January 1, 1991 and December 31, 1992 and matched term-born controls. Outcomes include educational attainment, employment, financial status, romantic partnering, living arrangements, parenthood, physical health and mental health, risk-taking behaviors, life satisfaction, and interpersonal relationships at 25 years. RESULTS: Data were available from 165 EP/ELBW and 127 control participants. Overall, there was little evidence for differences between the EP/ELBW and control groups on most comparisons after adjustment for social risk and multiple births. However, compared with controls, the EP/ELBW group was more likely to have their main source of income from government (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.21-5.13; P = .01) and to have never moved out of the parental home (aOR 2.13, 95% CI 1.27-3.58; P = .01), and fewer had ever engaged in smoking (aOR 0.52, 95% CI 0.28-0.98; P = .04), binge drinking (aOR 0.41, 95% CI 0.18-0.93; P = .03), or street drugs (aOR 0.56, 95% CI 0.32-0.98; P = .04). CONCLUSIONS: Aside from clinically important differences in main income source, leaving the parental home, and reduced risk-taking behavior, survivors born EP/ELBW in the era since surfactant was introduced are transitioning into adulthood similarly to term-born controls in some areas assessed but not all.

Management of bronchopulmonary dysplasia in Japan: A nationwide survey.

BACKGROUND: The incidence of bronchopulmonary dysplasia (BPD) and respiratory management practices for extremely low birth weight infants (ELBWIs) widely vary among institutions and countries. AIMS: To clarify the variation and characteristics of the current practices of Japanese neonatologists managing patients with BPD. STUDY DESIGN: Questionnaire-based survey. PARTICIPANTS: Level II and III perinatal centers certified by the Japan Society of Perinatal and Neonatal Medicine. OUTCOME MEASURES: Policies of the neonatal intensive care units (NICUs) regarding respiratory care and medications for BPD prevention and treatment. RESULTS: A total of 76 % of facilities (207/274) responded to our survey. The response rates of level III and II facilities were 91 % (102/112) and 35 % (105/296), respectively. INtubation-SURfactant-Extubation and Less Invasive Surfactant Administration methods were performed in 23 % (47/206) and 1 % (3/206) of facilities, respectively. For the prophylactic purpose, systemic and inhaled steroids were administered "frequently" or "occasionally" in 14 % (28/205) and 42 % (86/204) of NICUs, respectively. For the therapeutic purpose, systemic and inhaled steroids were administered "frequently" or "occasionally" in 84 % (171/204) and 29 % (59/204) of NICUs, respectively. Approximately half of the NICUs (99/202) used volume-targeted ventilation (VTV) "frequently" or "occasionally" in progressing BPD. High-frequency oscillation ventilation (HFOV) was used for progressing BPD "frequently" and "occasionally" in 89 % (180/202) of the facilities. CONCLUSIONS: Our study provided an overview and characteristics of BPD management in Japan in recent years. Noninvasive approaches with surfactant administration remain not widely used in Japan. HFOV is a widely accepted management for progressing BPD.

Neurodevelopmental Correlates of Brain Magnetic Resonance Imaging Abnormalities in Extremely Low-birth-weight Infants.

OBJECTIVE: To evaluate the relationship between impaired brain growth and structural brain abnormalities at term-equivalent age (TEA) and neurodevelopment in extremely low-birth-weight (ELBW) infants over the first 2 years. METHODS: ELBW infants born from 2009 through 2018 and undergoing brain magnetic resonance imaging (MRI) at TEA were enrolled in this retrospective cohort study. MRI scans were reviewed using a validated quali-quantitative score, including several white and gray matter items. Neurodevelopment was assessed at 6, 12, 18, and 24 months using the Griffiths scales. The independent associations between MRI subscores and the trajectories of general and specific neurodevelopmental functions were analyzed by generalized estimating equations. RESULTS: One hundred-nine ELBW infants were included. White matter volume reduction and delayed myelination were associated with worse general development (b = -2.33, P = .040; b = -6.88, P = .049 respectively), social skills (b = -3.13, P = .019; b = -4.79, P = .049), and eye-hand coordination (b = -3.48, P = .009; b = -7.21, P = .045). Cystic white matter lesions were associated with poorer motor outcomes (b = -4.99, P = .027), while white matter signal abnormalities and corpus callosum thinning were associated with worse nonverbal cognitive performances (b = -6.42, P = .010; b = -6.72, P = .021, respectively). Deep gray matter volume reduction correlated with worse developmental trajectories. CONCLUSIONS: Distinctive MRI abnormalities correlate with specific later developmental skills. This finding may suggest that TEA brain MRI may assist with neurodevelopmental prediction, counseling of families, and development of targeted supportive interventions to improve neurodevelopment in ELBW neonates.

Complication rates in very low and extremely low birth weight infants following laparotomy: a prospective study.

INTRODUCTION: Surgical site occurrences (SSO), including surgical site infection, dehiscence, and incisional hernia, are complications following laparotomy. SSO rates in premature neonates are poorly understood. We hypothesize that SSO rates are higher among extremely low birth weight (ELBW) infants compared to very low birth weight (VLBW) infants and strive to determine the optimal abdominal closure method for these infants. METHODS: We conducted a prospective observational study of infants < 1.5 kg (kg) undergoing laparotomy at two institutions from 1/1/2020 to 5/1/2022. Patients were grouped by weight and closure; SSO rates were computed and the association tested using Fisher's exact test. RESULTS: We identified 59 patients and 104 total operations. At initial surgery, 37 patients weighed < 1 kg (ELBW); 22 patients weighed 1-1.5 kg (VLBW). Complication rate for ELBW was 6(16%) vs. 2(9%) in VLBW, but not significant (p = 0.45). More complications followed a single-layer compared to a two-layer closure (18 vs. 2), but not significant (p = 0.30). CONCLUSIONS: SSO rates are higher for ELBW infants undergoing laparotomy, and fewer complications follow two-layer closure. However, these findings did not reach statistical significance. Further studies are needed to identify modifiable factors to reduce postoperative complications in these infants.

The effect of patient volume on mortality and morbidity of extremely low birth weight infants in Taiwan.

BACKGROUND: To assess whether the number of extremely low birth weight (ELBW) infants treated annually in neonatal intensive care units (NICUs) in Taiwan affects the mortality and morbidity of this patient population. METHODS: This retrospective cohort study included preterm infants with ELBW (≤1000 g). NICUs were divided into three subgroups according to the annual admissions of ELBW infants (low, ≤10; medium, 11-25; and high, >25). Perinatal characteristics, mortality, and short-term morbidities were compared between groups. RESULTS: A total of 1945 ELBW infants from 17 NICUs were analyzed (low-volume, n = 263; medium-volume, n = 420; and high-volume, n = 1262). After risk adjustments, infants from NICUs with low patient volumes were at a higher risk of death. The risk-adjusted odds ratios (aOR) for mortality were 0.61 (95% CI, 0.43-0.86) in the high-volume NICUs and 0.65 (95% CI, 0.43-0.98) in medium-volume NICUs, compared with infants admitted to low-volume NICUs. Infants in medium-volume NICUs had the lowest incidence of prenatal steroid exposure (58.1%, P < 0.001) and were associated with the highest risk of necrotizing enterocolitis (aOR, 2.35 [95% CI, 1.48-3.72]), severe intraventricular hemorrhage (aOR, 1.55 [95% CI, 1.01-2.28]), and bronchopulmonary dysplasia (aOR, 1.61 [95% CI, 1.10-2.35]). However, survival without major morbidity did not differ between the groups. CONCLUSION: The mortality risk was higher among ELBW infants admitted to NICUs with a low annual patient volume. This may emphasize the importance of systematically referring patients from these vulnerable populations to appropriate care settings.

Axillary skin crease incision versus conventional posterolateral incision in open repair of patent ductus arteriosus for extremely low birth weight infants: a retrospective study.

BACKGROUND: Thoracotomy with posterolateral incision (PLI) is commonly used for surgical repair of patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Some reports have described thoracotomy for PDA using an axillary skin crease incision (ASCI) in consideration of cosmetic problems such as surgical wounds and thoracic deformities, but the details remain unclear. METHODS: In this study, we performed clipping ligation by thoracotomy with ASCI for ELBW infants with PDA from 2011 to 2015 for the purpose of improving cosmetic results, and retrospectively compared the results with those for conventional PLI cases performed from 2016 to 2020. RESULTS: ASCI was found to be associated with serious surgical complications and showed a significant difference in outcome parameters only for surgery time, suggesting a safety problem for ASCI. Considering these results, PLI allows clipping of the nearby PDA from the thoracotomy wound while looking straight ahead, whereas the PDA in ASCI is positioned deep and oblique to the thoracotomy wound, so the clipping angle is limited and accurate completion of the procedure is difficult. CONCLUSIONS: Regarding PDA repair in ELBW infants, ASCI shows a high risk of serious surgical complications. Conventional PLI remains preferable for safe and accurate results.

A case of breast milk-acquired cytomegalovirus infection in an extremely low birth weight infant.

INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection. Preterm infants with postnatal CMV infections are susceptible to a variety of life-threatening conditions. CASE SUMMARY: Twin male infants were delivered via emergency caesarian section at 27 weeks' gestation secondary to maternal complete uterine rupture. The Apgar scores at 1 and 5 min were 1 and 1 for the older twin (Twin A) and 0 and 3 for the younger twin (Twin B). Their birth weights were 1203 g (+ 0.65SD) and 495 g (- 3.79SD) respectively. On day 41, laboratory blood test results for Twin B showed a moderate elevation in C-reactive protein (CRP), thrombocytopenia. CMV quantitative polymerase chain reaction (qPCR) tests in Twin B's urine and blood as well as in the mother's breast milk were positive, but stored, dried umbilical cord CMV qPCR tests were negative. Twin B was diagnosed with a postnatal CMV infection secondary to infected breast milk and ganciclovir was commenced on day 52. Treatment was switched to valganciclovir at 74 days of age, but a negative CMV-DNA level in the blood was not achieved. Postnatal CMV infection in this infant led to an exacerbation of pre-existing bronchopulmonary dysplasia (BPD) and he demised at 182 days of age. CONCLUSION: Postnatal cytomegalovirus infections may lead to exacerbations of BPD. Early use of raw breast milk in preterm infants should be done with careful consideration of this potential complication.

Proteinuria and Renal Dysfunction Due to Extremely Low Birth Weight in a Patient with Silver-Russell Syndrome.

A 36-year-old woman diagnosed with Silver-Russell syndrome during childhood presented to our department after a primary care physician suspected renal dysfunction. At birth, she had an extremely low weight (1210 g), and in childhood, she was diagnosed with Silver-Russell syndrome. At the age of 14 she was found to have proteinuria; however, the condition was never further examined. One month prior to her presentation to our department, the following were noted: 3+ urinary protein, 3.9 urinary protein/creatinine ratio, and 48 mL/min/1.73 m2 estimated glomerular filtration rate. Abdominal computed tomography revealed small kidneys difficult to visualize using ultrasound. Therefore, an open renal biopsy was performed. The renal biopsy revealed no significant findings in the glomerulus except glomerular hypertrophy, and the glomerular density in the cortical area was low (0.6/mm2). The patient was diagnosed with oligomeganephronia. Proteinuria and renal dysfunction were likely due to glomerular hyperfiltration resulting from a low nephron count caused by low birth weight. Silver-Russell syndrome is characterized by intrauterine growth retardation and additional developmental disorders after birth. Here, we detected oligomeganephronia following kidney biopsy in a patient with Silver-Russell syndrome. We suspect that a reduced number of nephrons due to low birth weight caused proteinuria and renal dysfunction.

Extended minimal enteral feeding and time to regain birth weight in extremely low-birth-weight infants.

BACKGROUND: Minimal enteral feeding after birth has been developed as a strategy to enhance the functional maturation of the gastrointestinal tract. This study aimed to examine the relationship between the duration of minimal enteral feeding and time to regain birth weight in extremely low-birth-weight infants. METHODS: This retrospective study included all extremely low-birth-weight infants born between January 2018 and December 2020. Infants with major congenital anomalies and conditions requiring surgery and those who died or received palliative care in the first 10 days of life were excluded from the analysis. Minimal enteral feeding courses were categorized as extended if the feeding was continued for > 72 hours and short if the feeding was < 72 hours. The primary measured outcome was the time taken to regain birth weight. RESULTS: Of 217 study infants, 180 received an extended minimal enteral feeding for > 72 h. The median time to regain birth weight was not significantly different between the extended and short minimal enteral feeding groups, median (IQR) was 10 (7-13) versus 8 (6-11), respectively (p = 0.15). Extended minimal enteral feeding is associated with a significant increase in the mean duration of the total parenteral nutrition, (21.3±10 versus 17.2±9.3 days; p = 0.021). Infants with prolonged minimal enteral feeding courses experienced non-significantly higher levels of necrotizing enterocolitis, late-onset sepsis, and retinopathy of prematurity. CONCLUSIONS: Extended minimal enteral feeding in extremely low-birth-weight infants may not affect the time taken to regain birth weight.

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.

Association between gastrointestinal perforation and patent ductus arteriosus in extremely-low-birth-weight infants: a retrospective study of our decade-long experience.

PURPOSE: Management of persistently patent ductus arteriosus (PDA) in extremely low-birth-weight infants (ELBWIs) requires attention due to the risk of tissue hypoperfusion. We investigated the association between PDA and gastrointestinal perforation. METHODS: We performed a retrospective chart review from 2012 to 2021. Preterm (≤ 32 weeks) ELBWIs with PDA after birth who developed necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and idiopathic gastric perforation were included; ELBWIs with congenital heart disease were excluded. Data were analyzed using chi-squared tests with Yates; correction, and Student's t test. RESULTS: Five hundred thirty-five preterm ELBWIs were analyzed, including 20 with NEC, 22 with FIP, and 1 with gastric perforation. In NEC and FIP, the ductus arteriosus remained open in 40% (4/10) and 63.6% (14/22) of cases, respectively, and cyclo-oxygenase inhibitor treatment showed poor efficacy (p = 0.492 and 0.240). The incidence of perforation in NEC (4/9 vs. 6/11, p = 0.653), mortality in NEC (3/4 vs. 3/6, p = 0.895) and FIP (6/14 vs. 3/8, p = 0.838) did not differ according to whether the PDA persisted or resolved. CONCLUSION: The presentation of PDA did not affect the mortality or morbidity of ELBWIs. However, it is essential to consider the possibility of gastrointestinal perforation due to decreased organ blood flow caused by ductal steal.

[A multicenter prospective cohort study of late-onset sepsis and its poor prognosis in very low birth weight infants].

Objective: To investigate the prevalence and poor prognosis of late-onset sepsis (LOS) in very low birth weight infant (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from Sina-Northern Neonatal Network (SNN). The general data, perinatal information and poor prognosis of 6 639 VLBWI, who were admitted to the 35 neonatal intensive care units from 2018 to 2021, were collected and analyzed. According to the occurrence of LOS during hospitalization, the VLBWI were assigned to the LOS group and non-LOS group. The LOS group was further divided into 3 subgroups according to the occurrence of neonatal necrotizing enterocolitis (NEC) and purulent meningitis. The Chi-square test or Fisher exact probability method, independent sample t test, Mann-Whitney U test and multivariate Logistic regression model were used to analyze the relationship between LOS and poor prognosis in VLBWI. Results: A total of 6 639 eligible VLBWI were enrolled, including 3 402 cases (51.2%) of males and 1 511 cases (22.8%) with LOS. The incidences of LOS in extremely low birth weight infants (ELBWI) and extremely preterm infants were 33.3% (392/1 176) and 34.2% (378/1 105), respectively. There were 157 cases (10.4%) who died in the LOS group and 48 cases (24.9%) in the subgroup of LOS complicated with NEC. Multivariate Logistic regression analysis showed that LOS complicated with NEC was associated with increased mortality and incidence of grade Ⅲ-Ⅳ intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), moderate or severe bronchopulmonary dysplasia (BPD), and extrauterin growth retardation (EUGR) (ORadjust=5.27, 2.59, 3.04, 2.04; 95%CI 3.60-7.73, 1.49-4.50, 2.11-4.37, 1.50-2.79; all P<0.01); LOS complicated with purulent meningitis was also associated with increased mortality and incidence of grade Ⅲ-Ⅳ IVH or PVL, and moderate or severe BPD (ORadjust=2.22, 8.13, 3.69, 95%CI 1.30-3.37, 5.22-12.67, 2.49-5.48; all P<0.01); the infants without NEC or purulent meningitis in the LOS group was only associated with increased incidence of moderate or severe BPD (ORadjust=2.20, 95%CI 1.83-2.65, P<0.001). After ruling out contaminated bacteria, a total of 456 cases showed positive blood culture, including 265 cases (58.1%) of Gram-negative bacteria, 126 cases (27.6%) of Gram-positive bacteria, and 65 cases (14.3%) of fungi. The most common pathogenic bacteria was Klebsiella pneumoniae (n=147, 32.2%), followed by coagulase-negative Staphylococcus (n=72, 15.8%) and subsequently Escherichia coli (n=39, 8.6%). Conclusions: The incidence of LOS is high in VLBWI. Klebsiella pneumoniae is the most common pathogenic bacteria, followed by coagulase-negative Staphylococcus and Escherichia coli. LOS is associated with a poor prognosis for moderate to severe BPD. The prognosis of LOS complicated with NEC is poor with the highest mortality, and the risk of brain damage is significantly increased when LOS complicated with purulent meningitis.

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.

Postnatal growth and body composition in extremely low birth weight infants fed with individually adjusted fortified human milk: a cohort study.

This cohort study aimed to evaluate the impact of an individualised nutritional care approach combining standardised fortification with adjustable fortification on postnatal growth and body composition in extremely low birth weight (ELBW) infants. We included ELBW infants admitted to a neonatal intensive care unit and still hospitalised at 35 weeks postmenstrual age (PMA). The fortification of human milk was standardised (multicomponent fortifier) between 70 mL/kg/day and full enteral feeding, and then individualised using adjustable fortification. When weight gain was below 20 g/kg/day, protein or energy was added when serum urea was below or above 3.5 mmol/L, respectively. Postnatal growth failure (PNGF) was defined as being small for gestational age at discharge and/or when the Z-score loss between birth and discharge was higher than 1. Body composition was assessed between 35 and 41 weeks of PMA. Among the 310 ELBW infants included, the gestational age of birth was 26.7 ± 1.8 weeks, and the birth weight was 800 ± 128 g. The mean Z-score difference between birth and discharge was moderately negative for the weight (-0.32), more strongly negative for length (-1.21), and almost nil for head circumference (+ 0.03). Only 27% of infants presented PNGF. At discharge, fat mass was 19.8 ± 3.6%. Multivariable analysis showed that the proportion of preterm formula received and gestational age at birth were independently associated with the percentage of fat mass.  Conclusion: The individualised nutritional care approach applied herein prevented postnatal weight loss in most infants, limited length growth deficit, and supported excellent head circumference growth. What is Known: • At least half of extremely low birth weight infants are small for gestational age at discharge and postnatal growth deficit has been associated with impaired neurocognitive and renal development. • Human milk is the main milk used in neonatology and, although fortification of human milk is a standard of care, there is no consensus regarding the optimal fortification strategy to be adopted. What is New: • Using an approach combining standardised fortification followed by individualised adjustable fortification limited postnatal growth deficit for body weight and head circumference. Postnatal growth failure is not a fatality in extremely low birth weight infants. • Each additional gestational age week at birth resulted in a decrease in fat mass percentage at discharge, which was higher than in foetuses of the same gestational age, likely representing a necessary adaptation to extra-uterine life.

[Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China].

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Postnatal corticosteroids and developmental outcomes in extremely preterm or extremely low birth weight infants: The Victorian Infant Collaborative Study 2016-17 cohort.

AIM: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long-term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. METHODS: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016-2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. RESULTS: Seventy-six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92-3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) -1.3 (-2.7, 0.1) and motor composite score adjusted coefficient (95% CI) -1.3 (-2.8, 0.2). CONCLUSION: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes.