Changes in Lung Function Among Infants Born Extremely Preterm over a 20-Year Period in the Post-Surfactant Era: A Retrospective Study.

Lung function was assessed at 8 years in 308 infants born extremely preterm between 1994 and 2013. Although lung function of those infants born at 22 through 25 weeks remained unchanged, those who were born at 26-27 weeks showed a significant improvement over the past 2 decades.

Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs. RESULTS: This review included three RCTs (162 infants). There were no significant differences between the prophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.

Skin-to-Skin Contact and Diaphragm Electrical Activity in Preterm Infants During Noninvasive Pressure Control.

BACKGROUND: Skin-to-skin contact (SSC) is widely implemented in the neonatal intensive care unit (NICU) due to its established role in reducing mortality and morbidity. However, the impact of SSC on diaphragmatic electrical activity (Edi) in premature infants undergoing noninvasive pressure control (NIV-PC) for respiratory management remains insufficiently explored. PURPOSE: To assess the effects of SSC on Edi and vital signs in preterm infants managed with NIV-PC. METHODS: A prospective, observational, crossover study was conducted, involving preterm infants admitted to a level III NICU between May 2020 and August 2021, who were receiving respiratory support with NIV-PC. Data were collected at 3 distinct time points: before SSC (pre-SSC period), during SSC (SSC period), and after SSC (post-SSC period). Thirty-minute periods of stable data were extracted for analysis. RESULTS: A total of 21 SSC sessions were performed on 14 preterm infants, with a median age at the initiation of SSC of 62 days. The median (interquartile range) Edi peak (in microvolts) before, during, and after SSC was 7.1 (5.8-10.8), 6.8 (4.3-8.8), and 7.1 (5.5-8.8), respectively. No statistically significant differences were observed in Edi peak or minimum values during SSC, when compared with the periods before and after the SSC procedure. Likewise, no significant changes were noted in respiratory rate, oxygen saturation, heart rate, or the incidence of apnea. IMPLICATIONS FOR PRACTICE AND RESEARCH: SSC in preterm infants undergoing NIV-PC does not exacerbate their clinical condition. Further investigations involving diverse patient cohorts are warranted.

The Association between Early Gram-Negative Bacteria in Tracheal Aspirate Cultures and Severe Bronchopulmonary Dysplasia among Extremely Preterm Infants Requiring Prolonged Ventilation.

OBJECTIVE: The study aimed to evaluate the association between bronchopulmonary dysplasia (BPD) development at 36 weeks' postmenstrual age (PMA) and Gram-negative bacteria in tracheal aspirate cultures among extremely preterm infants. STUDY DESIGN: This study has a retrospective cohort. Patients were 155 infants aged less than or equal to 26 gestational weeks who were admitted to the neonatal intensive care unit of Osaka Women's and Children's Hospital from 2009 to 2018. Primary outcome was respiratory outcomes expressed as BPD development.Multivariable logistic regression analysis was used to identify neonatal and bacterial factors associated with BPD. RESULTS: After adjusting for gestational age, birth weight, sex, chorioamnionitis, Gram-positive cocci (GPC) and Gram-negative rods (GNRs) in tracheal aspirate cultures within 28 days after birth, GNRs were significantly associated with BPD development (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.68-8.94). In contrast, GPCs were not associated with BPD development (OR: 0.47, 95% CI: 0.05-1.61). CONCLUSION: Gram-negative bacteria in tracheal cultures within 28 days of birth are associated with BPD development in infants aged less than or equal to 26 gestational weeks. KEY POINTS: · BPD is a factor for morbidity in extremely preterm infants.. · Respiratory infection is an adverse outcome of BPD.. · GNRs in tracheal cultures soon after birth disturb BPD development.. · GPC was not associated with BPD development..

Feasibility of portable capnometer for mechanically ventilated preterm infants in the delivery room.

This study aimed to determine whether a specific portable capnometer (EMMA™) can facilitate the maintenance of an appropriate partial pressure of arterial carbon dioxide (PaCO2) in intubated preterm infants in the delivery room. This study included preterm infants with a gestational age of 26 + 0 to 31 + 6 weeks who required intubation in the delivery room. We prospectively identified 40 infants who underwent the EMMA™ monitoring intervention group and 43 infants who did not undergo monitoring (historical control group). PaCO2 was evaluated either at admission in the neonatal intensive care unit or at 2 h after birth. The proportion of infants with an appropriate PaCO2 (35-60 mmHg) was greater in the intervention group than in the control group (80% vs. 42%; p = 0.001). There were no significant differences in the rate of accidental extubation (5.0% vs. 7.0%, p = 1.00) or in the proportion of infants with an appropriate PaCO2 among infants whose birth weight was < 1000 g (54% vs. 40%, p = 0.49). However, among infants whose birth weight was ≥ 1000 g, the PaCO2 tended to be more appropriate in the intervention group than in the control group (93% vs. 44%; p < 0.001).Conclusion: The EMMA™ facilitated the maintenance of an appropriate PaCO2 for mechanically ventilated preterm infants, especially infants with birth weight ≥1000 g, in the delivery room. What is Known: • An inappropriate partial pressure of arterial carbon dioxide has been associated with intraventricular hemorrhage in preterm infants. • There is a need to appropriately control the partial pressure of arterial carbon dioxide in preterm infants. What is New: • This is the first report regarding the feasibility of a portable capnometer, the EMMA™, in the delivery room. • The EMMA™ may be considered a feasible monitoring device in the delivery room for intubated preterm infants, especially infants with birth weight ≥1000 g.

Long-term outcomes of children with neonatal transfer: the Japan Environment and Children's Study.

This study aimed to evaluate the association of neonatal transfer with the risk of neurodevelopmental outcomes at 3 years of age. Data were obtained from the Japan Environment and Children's Study. A general population of 103,060 pregnancies with 104,062 fetuses was enrolled in the study in 15 Regional Centers between January 2011 and March 2014. Live-born singletons at various gestational ages, including term infants, without congenital anomalies who were followed up until 3 years were included. Neurodevelopmental impairment was assessed using the Ages and Stages Questionnaire, third edition (ASQ-3) at 3 years of age. Logistic regression was used to estimate the adjusted risk and 95% confidence interval (CI) for newborns with neonatal transfer. Socioeconomic and perinatal factors were included as potential confounders in the analysis. Among 83,855 live-born singletons without congenital anomalies, 65,710 children were studied. Among them, 2780 (4.2%) were transferred in the neonatal period. After adjustment for potential confounders, the incidence of neurodevelopmental impairment (scores below the cut-off value of all 5 domains in the ASQ-3) was higher in children with neonatal transfer compared with those without neonatal transfer (communication: 6.5% vs 3.5%, OR 1.42, 95% CI 1.19-1.70; gross motor: 7.6% vs 4.0%, OR 1.26, 95% CI 1.07-1.49; fine motor: 11.3% vs 7.1%, OR 1.19, 95% CI 1.03-1.36; problem solving: 10.8% vs 6.8%, OR 1.29, 95% CI 1.12-1.48; and personal-social: 6.2% vs 2.9%, OR 1.52, 95% CI 1.26-1.83).   Conclusion: Neonatal transfer was associated with a higher risk of neurodevelopmental impairment at 3 years of age. What is Known: • Neonatal transfer after birth in preterm infants is associated with adverse short-term outcomes. • Long-term outcomes of outborn infants with neonatal transfer in the general population remain unclear. What is New: • This study suggests that neonatal transfer at birth is associated with an increased risk of neurodevelopmental impairment. • Efforts for referring high-risk pregnant women to higher level centers may reduce the incidence of neonatal transfer, leading to improved neurological outcomes in the general population.

The status of chronic lung disease diagnosis in Japan: Secondary publication.

BACKGROUND: In Japan, the definition and classification of neonatal chronic lung disease (CLD) used for its diagnosis are a combination of those used in Japan and abroad. METHODS: To clarify the current state of CLD diagnosis, a questionnaire survey was conducted. RESULTS: Half of the patients of the medical centers included in the study were diagnosed with CLD in real time, while the other half were diagnosed after discharge. In addition, in approximately 70% of the facilities, diagnosis was made after discussions various among medical teams. In approximately 80% of the centers, the chest radiography used for CLD diagnosis were evaluated by multiple doctors. Furthermore, some centers used chest X-rays that were taken at approximately 28 days of age for CLD diagnosis, whereas at other facilities, diagnosis was made regardless of time at which the chest radiography were obtained. Only a small number of centers have established criteria for determining the necessity of oxygen at the corrected age of 36 weeks, and the target saturation of peripheral oxygen levels also tend to vary for each facility. Whether the conditions wherein the patient receives respiratory support for apnea or respiratory tract diseases should be considered as CLD also differed among the facilities. CONCLUSIONS: It is necessary to reassess the definition and classification of CLD in Japan to accurately evaluate and improve the quality of respiratory management based on the long-term prognosis.

Pregnancy outcomes after preterm premature rupture of membranes: The Japan Environment and Children's Study.

AIM: To evaluate the pregnancy outcomes of preterm premature rupture of membranes (preterm PROM; PPROM) by gestational age. METHODS: This cohort study analyzed data from the Japan Environment and Children's Study. Pregnancy outcomes were documented using descriptive statistics. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of complications. RESULTS: Data were collected for 104 062 fetuses, and 99 776 were eligible for inclusion. The incidences of early (18-23 weeks) and late (24-36 weeks) PPROM were 0.1% (n = 102) and 1.2% (n = 1205), respectively. Of the 1307 cases, 66 (5.0%) resulted in miscarriage or stillbirth. Overall, 85.6% (1119/1307) resulted in preterm births, and 9.3% (122/1307) in term births. There was a higher incidence of oligohydramnios (OR 6.82, 95% CI 4.07, 11.4; OR 2.42, 95% CI 1.72, 3.40), intrauterine infection (OR 11.9, 95% CI 7.06, 19.9; OR 4.39, 95% CI 3.01, 6.41), cesarean delivery (OR 3.31, 95% CI 2.32, 4.71; OR 1.34, 95% CI 0.97, 1.85), placental abruption (OR 5.57, 95% CI 2.30, 13.5; OR 5.40, 95% CI 3.58, 8.14), and 5-min Apgar score <7 (OR 35.3, 95% CI 21.5, 57.9; OR 2.66, 95% CI 1.75, 4.05) for early and late, compared to no, PPROM, respectively. Miscarriage or stillbirth was higher in early (OR 5.84, 95% CI 3.72, 9.15) and lower in late (OR 0.21, 95% CI 0.06, 0.68) compared to those without PPROM. CONCLUSIONS: This study described the epidemiology of pregnancy outcomes of early (occurring at the limit of viability) and late PPROM.

Urine Desmosine as a Novel Biomarker for Bronchopulmonary Dysplasia and Postprematurity Respiratory Disease in Extremely Preterm or Low Birth Weight Infants.

OBJECTIVE: This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants. STUDY DESIGN: This study recruited 37 EP (22-27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis. RESULTS: Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67-105) and PRD (OR, 13.8; 95% CI, 1.31-144). CONCLUSION: Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants. KEY POINTS: · Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.. · Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.. · Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants..

Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.

Infantile liver failure syndrome type 1 (ILFS1) is a recently recognized autosomal recessive disorder caused by deleterious mutations in the leucyl-tRNA synthetase 1 gene (LARS1). The LARS1 enzyme is responsible for incorporation of the amino acid leucine during protein polypeptide synthesis. Individuals with LARS1 mutations typically show liver failure from infancy to early childhood during periods of illness or other physiological stress. While 25 patients from 15 families with ILFS1 have been reported in the literature, histological reports from autopsy findings are limited. We report here a premature male neonate who presented with severe intrauterine growth retardation, microcytic anemia, and fulminant liver failure, and who was a compound heterozygote for two novel deleterious mutations in LARS1. An autopsy showed fulminant hepatitis-like hepatocellular injury and fibrogenesis in the liver and a lack of uniformity in skeletal muscle, accompanied by the disruption of striated muscle fibers. Striking dysgenesis in skeletal muscle detected in the present case indicates the effect of LARS1 functional deficiency on the musculature. Whole-exome sequencing may be useful for neonates with unexplained early liver failure if extensive genetic and metabolic testing is inconclusive.

Availability of portable capnometers in children with tracheostomy.

BACKGROUND: A capnometer is a noninvasive monitor that is used to assess patients' respiratory status. This study was performed to evaluate the availability of a portable capnometer in children with tracheostomy. METHODS: This retrospective study included children with tracheostomy who were treated at the Osaka Women's and Children's Hospital Osaka, Japan, from 1 September 2018 to 31 October 2019. We assessed the correlation between the partial pressure of venous carbon dioxide (PvCO2 ) and end-tidal carbon dioxide tension (EtCO2 ) using a portable capnometer (EMMA; Masimo, Irvine, CA, USA). RESULTS: Nine infants and 43 simultaneous PvCO2 -EtCO2 pairs were analyzed. The correlation coefficient of these pairs was 0.87 (95% confidence interval, 0.77-0.93; P < 0.001). The Bland-Altman plot showed that EtCO2 was on average 10.0 mmHg lower than its paired PvCO2 value (95% limits of agreement, 1.0-19.1). The difference between PvCO2 and EtCO2 was significantly greater in patients on ventilators. CONCLUSIONS: The portable capnometer evaluated in this study (EMMA) was readily available and useful for assessment of the respiratory condition in children with tracheostomy.

Association between amount of dopamine and infections in extremely preterm infants.

This study aimed to assess the effect of dopamine on the development of infections after birth in extremely preterm infants. We retrospectively identified 258 extremely preterm infants (born at < 28 gestational weeks) between July 2009 and December 2018 in a tertiary neonatal intensive care unit (NICU). We extracted data on potential risk factors for infection, total amount of dopamine, and infection history during NICU stay for each infant. We compared the infection group with the non-infection group, and used the Cox proportional hazard regression analysis to identify risk factors for infection during NICU stay. After adjustment for all potential risk factors, factors that significantly affected development of infection were gestational age (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.55-0.89; p = 0.004) and total amount of dopamine (HR, 1.04; 95% CI 1.02-1.07; p = 0.002). The receiver operating characteristic curve of total amount of dopamine for infection suggested that total amount of dopamine greater than 7.271 mg/kg predicted infection development with 80.4% sensitivity and 41.7% specificity.Conclusion: A large amount of dopamine can increase infections in extremely preterm infants. We should avoid using a large amount of dopamine and remain aware of the potential development of infections in extremely preterm infants. What is Known: • Inotropes are often used for extremely preterm infants and dopamine is the most commonly used inotrope. • However, it is suggested that dopamine affects the immune system and related infections. What is New: • This is the first study of the association between the amount of dopamine and infection in extremely preterm infants. • We should avoid using a large amount of dopamine in extremely preterm infants.

Weight-Based Estimation of Insertion Length of the Nasogastric Tube in Extremely Low Birth-Weight Infants.

BACKGROUND: Nasogastric (NG) tubes are used in the neonatal intensive care unit (NICU) for various indications. However, evidence of the best practice for estimating the NG tube insertion length in extremely low birth-weight (ELBW) infants is limited. PURPOSE: To determine a weight-based estimation formula of NG tube length in ELBW infants. METHODS: This prospective study was performed at a single-center level III neonatal intensive care unit. Low birth-weight infants admitted between May 2009 and May 2010 who required radiography for clinical reasons were included. Radiographs of participants whose current body weights (BWs) were less than 2500 g were reviewed, and the appropriate ideal insertion length of the NG tube adjusted based on radiographs and the infant's current BW was assessed. A regression model was used to determine the ideal insertion length of the NG tube with respect to the current BW. RESULTS: Overall, 533 radiographs (152 patients weighing 422-2486 g) were analyzed. Among the patients, 246 had BWs less than 1000 g and 287 had BWs more than 1000 g. Formulas that predicted NG tube length (centimeters) were derived as follows: (5 × weight [kg] + 10 [BW < 1.0 kg]) or (3 × weight [kg] + 12.5 [1.0 < BW <2.5 kg]). IMPLICATIONS FOR PRACTICE: The application of the weight-based formula for estimating the NG tube length derived from the present study together with commonly used morphological methods may improve the accuracy of the NG tube insertion procedure in ELBW infants. IMPLICATIONS FOR RESEARCH: Further studies in other cohorts are needed.

Impact of Time to Neonatal Transport on Outcomes of Transient Tachypnea of the Newborn.

OBJECTIVE: To assess effects of neonatal transport on transient tachypnea of the newborn (TTN) in outborn term neonates. STUDY DESIGN: This retrospective cohort study included 66 term neonates diagnosed with TTN and transported to the Osaka Women's and Children's Hospital neonatal intensive care unit between January 2003 and March 2018. A multivariate logistic regression analysis identified perinatal and neonatal transport factors associated with adverse short-term outcomes defined as mechanical ventilation >48 hours, continuous positive airway pressure >72 hours, pulmonary hemorrhage, and requirement for inhaled nitric oxide, thoracentesis, or surfactant replacement therapy. RESULTS: A lower gestational age (GA) (37.7 [37.2, 38.3] vs. 39.6 [37.8, 40.3] weeks, p = 0.002), longer time to neonatal transport (10.0 [4.3, 25.5] vs. 5.5 [2.7, 9.7] hours, p = 0.01), and higher respiratory rates during transport (70 [60, 85] vs. 60 [55, 78.8] breaths/min, p = 0.04) were significantly associated with adverse short-term outcomes. After adjusting for GA, sex, cesarean section, and time to neonatal transport, GA (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.24-0.87) and time to neonatal transport (OR, 1.07; 95% CI, 1.01-1.13) were significantly associated with adverse outcomes. CONCLUSION: Short-term adverse prognosis of TTN is strongly associated with a lower GA and longer time between birth and neonatal transport.

Mesenteric hernia causing bowel obstruction in very low-birthweight infants.

Internal hernia through a mesenteric defect, called mesenteric hernia, is an uncommon cause of acute intestinal obstruction in newborns. Strangulated mesenteric hernia results in intestinal necrosis or perforation and progressive deterioration with fatal outcome, especially when it occurs in low-birthweight infants. We report two very low-birthweight (VLBW) infants, who presented with acute intestinal obstruction related to mesenteric defect. The initial diagnosis was meconium obstruction in those cases, which is a common cause of bowel obstruction occurring in VLBW infants. Correct diagnosis of mesenteric hernia was difficult in these cases because of rapid deterioration and non-specific radiological findings. Awareness of the possibility of rare mesenteric hernia causing acute intestinal obstruction and surgical intervention in an appropriate timeframe are important for rescuing VLBW infants with such organic abnormalities.

Application of transcutaneous carbon dioxide tension monitoring with low electrode temperatures in premature infants in the early postnatal period.

OBJECTIVE: The aim of this article is to evaluate the accuracy, precision, and safety of transcutaneous carbon dioxide tension (TcPCO2) monitoring at different electrode temperatures in preterm infants in the early postnatal period. STUDY DESIGN: A total of 26 neonates with a median birth weight of 974 g (432-1,694 g) and gestational age of 28.0 weeks (26.1-31.3 weeks) were studied in the first 5 days of life. A total of 252 simultaneous pairs (TcPCO2 and arterial carbon dioxide tension [PaCO2]) were analyzed at 38, 39, and 40°C at 26 and 27 weeks, and at 38, 39, 40, and 42°C at 28 to 31 weeks. RESULTS: The mean difference of TcPCO2 and PaCO2 (bias) increased from 3.93 mm Hg at 42°C to 5.64 mm Hg at 40°C, 6.58 mm Hg at 39°C, and 6.07 mm Hg at 38°C. Standard deviation (SD) of the bias increased from 4.17 mm Hg at 42°C to 4.76 mm Hg at 40°C, 5.29 mm Hg at 39°C, and 5.07 mm Hg at 38°C. Adverse skin lesions were not observed. CONCLUSION: TcPCO2 measurements are the most accurate and precise at an electrode temperature of 42°C. However, in premature babies, monitoring at 38, 39, and 40°C is possible provided a bias correction of 6 mm Hg and SD of 5 mm Hg are applied.

Postneonatal mortality of severely small for gestational age extremely low birth weight infants.

BACKGROUND: Infants born with weights below the 10th percentile of the expected birth weight for gestational age, defined as small for gestational age (SGA), have an increased risk of neonatal mortality and prematurity-related complications. However, the relationship between SGA and postneonatal (28 days to <1 year) mortality among extremely low birth weight infants (ELBWIs) remains uncertain. Hence, this study aimed to investigate the association between birth weight percentiles and postneonatal mortality in ELBWIs. METHODS: A cohort of ELBWIs with a gestational age greater than 23 weeks who were admitted to Osaka Women's and Children's Hospital between 2008 and 2019 were considered eligible. Infants with major congenital anomalies, those large for their gestational age, or those who died within 28 days of birth were excluded. Baseline characteristics and outcomes of the three groups of ELBWIs-severe SGA (sSGA; birth weight, <3rd percentile), moderate SGA (mSGA; birth weight, 3rd to <10th percentile), and appropriate for gestational age (AGA; birth weight, 10th to <90th percentile)-were compared. Logistic regression analysis was used to identify perinatal factors associated with postneonatal mortality in sSGA infants. RESULTS: sSGA ELBWIs demonstrated higher incidence of meconium obstruction (25% vs. 8.3% vs. 7.6%, P < 0.001), cholestasis (21% vs. 4.2% vs. 9.7%, P < 0.003), and postneonatal mortality (7.3% vs. 0% vs. 0.7%, P < 0.004) than mSGA and AGA ELBWIs. In the logistic regression analysis, cholestasis (odds ratio, 30.1; 95% confidence interval, 2.98-304) and sepsis (odds ratio, 13.5; 95% confidence interval, 1.06-173) were significantly related to postneonatal mortality among ELBWIs with sSGA. The leading cause of postneonatal mortality in sSGA ELBWIs was liver failure (55.5%). CONCLUSION: sSGA ELBWIs exhibited a higher rate of postneonatal mortality compared to mSGA and AGA ELBWIs. Therefore, strategies aimed at preventing liver dysfunction in severely cholestatic ELBWIs with sSGA are necessary.

Neurodevelopmental outcomes at age 3 years after moderate preterm, late preterm and early term birth: the Japan Environment and Children's Study.

OBJECTIVE: To assess the association between gestational age classification at birth and the risk of neurodevelopmental impairments at age 3 years. DESIGN: Cohort study using the Japan Environment and Children's Study database. PATIENTS: A total of 86 138 singleton children born without physical abnormalities at 32-41 weeks of gestation enrolled between January 2011 and March 2014. MAIN OUTCOME MEASURES: Neurodevelopmental impairment, evaluated using the Ages and Stages Questionnaire (third edition). METHODS: Logistic regression analysis was used to evaluate the risk of neurodevelopmental impairment in moderate preterm, late preterm and early term children compared with term children after adjusting for socioeconomic and perinatal factors. RESULTS: The respective adjusted ORs (95% CIs) of incidence of scores below the cut-off value (<-2.0 SD) at age 3 years for moderate preterm, late preterm and early term births, compared with full-term births, were as follows: communication, 2.40 (1.54 to 3.73), 1.43 (1.19 to 1.72) and 1.11 (1.01 to 1.21); gross motor, 2.55 (1.69 to 3.85), 1.62 (1.36 to 1.93) and 1.20 (1.10 to 1.30); fine motor, 1.93 (1.34 to 2.78), 1.55 (1.35 to 1.77) and 1.08 (1.01 to 1.15); problem solving, 1.80 (1.22 to 2.68), 1.36 (1.19 to 1.56) and 1.07 (1.00 to 1.14) and personal-social, 2.09 (1.29 to 3.40), 1.32 (1.07 to 1.63) and 1.00 (0.91 to 1.11). CONCLUSION: Moderate preterm, late preterm and early term births were associated with developmental impairment at age 3 years compared with full-term births, with increasing prematurity. Careful follow-up of non-full-term children by paediatricians and other healthcare providers is necessary for early detection of neurodevelopmental impairment and implementation of available intervention.