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..

Intrauterine Ureaplasma is associated with small airway obstruction in extremely preterm infants.

BACKGROUND: The long-term follow-up of lung function (LF) in extremely preterm (EP) infants with bronchopulmonary dysplasia (BPD) has shown a worldwide increase in small airway obstructions (SAO). OBJECTIVES: We investigated the relationships between intrauterine Ureplasma infection in EP infants and bubbly/cystic lung, BPD, and SAO at school age. METHODS: Placental pathology, placental Ureaplasma DNA (pU-DNA), and cord blood immunoglobulin M (IgM) (C-IgM) were investigated in 360 EP infants born from 1981 to 2004. Maternal amniotic inflammatory response (M-AIR) scores and hemosiderin deposition (HD) were estimated in the chorioamnion. The study subjects were divided into groups based on their M-AIR scores. Their LF at school age was compared with those of 33 healthy siblings. FINDINGS: pU-DNA and C-IgM were significantly related to SAO at school age (p < 0.012). M-AIR score 3 and pU-DNA >1000 units had an odds ratio (OR) of 35 (95% confidence interval: 10-172) and 18 (5.6-67) for bubbly/cystic lung, and 11 (3.1 - 43) and 31 (4.5-349) for severe BPD, and 5.3 (2.1-11) and 12 (2.4-74) for SAO, respectively. The ORs of surfactant treatment, BPD grade III, O2 at 40 weeks, HD, and C-IgM >30 mg/dl for SAO were 0.21 (0.075-0.58), 5.3 (2.1-15), 2.5 (1.4-4.6), 3.6 (1.5-9.1) and 2.5 (1.0-5.2). 84% (90/107) SAO infants showed no or mild BPD in infancy, and 61% of infants had no severe CAM. CONCLUSION: Our long-term cohort study of LF in EP infants revealed that intrauterine Ureaplasma was associated with bubbly/cystic lung, severe BPD, and SAO at school age.

Epidemiology of Congenital Rubella Syndrome Related to the 2012-2013 Rubella Epidemic in Japan.

This study assessed the epidemiological characteristics of 45 congenital rubella syndrome cases in Japan following the 2012-2013 rubella epidemic. Rubella still poses significant health burdens and the uptake of rubella-containing vaccines among women of childbearing age should be improved.

Japanese original delayed hepatitis B vaccination provides adequate immunogenicity against mother-to-child hepatitis B virus infection in preterm infants: A nationwide survey in Japan.

OBJECTIVE: We aimed to evaluate immunogenicity following Japanese original delayed hepatitis B (HB) vaccinations for prevention of mother-to-child HB infection in preterm infants. METHODS: A nationwide survey in Japan was conducted at certified neonatology facilities in 2014. Eighty-four preterm infants born from a serum hepatitis B surface (HBs) antigen-positive mother were included. We collected data on the following parameters: gestational age, birth weight (BW), age at HB vaccination, age at examination of serum anti-HBs titer, and serum anti-HBs titer. The delayed HB vaccination schedule was 3 doses of HB vaccines at 2, 3 and 5 months of age. A seropositive immunogenic response to HB vaccination was defined as an anti-HBs titer ≥10 mIU/mL. Seropositive rates were calculated in all participants. Four subgroups based on BW were as follows: <1000 g (n = 13), 1000-1499 g (n = 16), 1500-1999 g (n = 26), and ≥2000 g (n = 29). RESULTS: Among 84 preterm infants who completed the delayed vaccination schedule, 82 (98%) achieved seropositive anti-HBs titer at a median age of 6 months. Seropositive rates of infants <1000 g, 1000-1499 g, 1500-1999 g, and ≥2000 g were 92%, 94%, 100%, and 100%, respectively. CONCLUSION: The Japanese original delayed HB vaccinations achieved sufficient seropositive rates in preterm infants and provide immunogenicity against mother-to-child HB infection.

Development of a Novel Algorithm to Detect Atrial Fibrillation Using an Automated Blood Pressure Monitor With an Irregular Heartbeat Detector.

BACKGROUND: Atrial fibrillation (AF), which contributes to an increased risk of stroke, frequently remains undetected, suggesting an unmet need for easier and more reliable AF screening. The reports on screening AF using an Omron blood pressure (BP) monitor with an irregular heartbeat (IHB) detector show inconsistent results, so the aim of this study was to develop a novel algorithm to accurately diagnose AF with 3 BP measurements using an Omron automated BP monitor with IHB detector.Methods and Results:In total, 303 general cardiac patients were included. Real-time single-lead ECG revealed AF in 44 patients. BP measurement was performed 3 times per patient using the Omron BP monitor HEM-907, and the number of IHBs detected was recorded. Based on these data, we developed the following algorithm: ≥1 IHB is detected during at least 2 of 3 BP measurements and the maximum number of IHBs detected is ≥2. Using this algorithm, we achieved a sensitivity of 95.5% and specificity of 96.5%, for diagnosing AF. CONCLUSIONS: The novel algorithm with 3 BP measurements using the Omron automated BP monitor with IHB detector showed high sensitivity and specificity for diagnosing AF in general cardiac patients.

Physical fitness of non-disabled school-aged children born with extremely low birth weights.

BACKGROUND: The assessment of long-term outcomes in survivors born with extremely low birth weights (ELBWs) has become increasingly important. However, little has been reported on the physical fitness of non-disabled school-aged children born with ELBWs. AIMS: To assess the physical fitness of non-disabled school-aged children born with ELBWs. STUDY DESIGN: Retrospective cohort study. SUBJECTS: We analyzed 169 ELBW infants without cerebral palsy or intellectual disability (based on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) Full Scale intelligence quotient (IQ) test < 70). OUTCOME MEASURES: Physical fitness was assessed using the grip strength, sit-up repetitions, sit & reach, side steps, standing long jump, and softball throw tests. T-scores were calculated using national survey data. RESULTS: The T-scores for the grip strength, sit-up repetitions, sit & reach, side steps, standing long jump, softball throw tests, and the overall T-score were 43.7 ±â€¯7.5, 44.2 ±â€¯10.5, 46.0 ±â€¯9.7, 40.9 ±â€¯8.0, 40.0 ±â€¯9.8, 42.4 ±â€¯8.1, and 42.9 ±â€¯5.5, respectively. After adjusting for other age-related factors, the height (SD score), WISC-III Performance IQ score, and percent predicted forced vital capacity (FVC) independently predicted the overall T-scores. Their standardized partial regression coefficients (ß) were 0.334 (p = 0.009), 0.190 (p = 0.022), and 0.187 (p = 0.032), respectively. CONCLUSIONS: Our cohort's physical fitness at approximately 8 years of age was significantly impaired compared to average Japanese children of the same age. Height, FVC, and Performance IQ independently predicted physical fitness, with height being the strongest predictor.

Nationwide survey of neonatal invasive fungal infection in Japan.

Invasive fungal infection (IFI) is a life-threating infectious disease in high-risk neonates. Strategies for the treatment and prevention of IFI in neonates in Japan remain unclear. We conducted a nationwide retrospective survey to determine IFI incidence between January 2014 and October 2015. Primary survey questionnaires were submitted to 309 medical facilities that regularly treat high-risk neonates. The questionnaire assessed IFI incidence during the study period, methods for preventing fungal infection in early delivery neonates, and methods for preventing mother-to-child fungal transmission. The secondary questionnaire was for facilities that had IFI cases and replied to the primary questionnaire. In total, 128 medical facilities (41.4%) completed the primary questionnaire, 17/128 facilities recorded 23 proven or probable IFI cases. Estimated annual IFI incidence was 0.33/1000 live births of hospitalized neonates. Patient data at IFI onset were available for all 23 patients. Birth weight was < 1000 g in 18 patients. Causative microorganisms were identified in 22 patients. Candida species (n = 21) were the most common pathogens, and one patient had mucormycosis. The mortality rate was 17.4%. Regarding neonatal fungal prophylaxis, 55/128 facilities (43.0%) reported administering therapy. The most frequently used prophylactic drugs were fluconazole, then micafungin. Fungal prophylaxis for mothers who showed fungal colonization was performed in 30/128 facilities (23.4%). Oxiconazole vaginal tablets were most commonly used as prophylaxis for high-risk mothers. In Japan, the diagnosis, treatment, and prevention of neonatal IFI varied. Continuous surveillance and treatment regimen for neonatal IFI are required to improve outcomes in high-risk neonates.

Trans fatty acid accumulation in the human placenta.

Trans fatty acid may impair fetal growth and infant neurodevelopment, but the quantity in a placenta and human tissues remains unknown. To address the issue, a simple and reliable method of quantification is needed. We established a method of quantifying trans-octadecenoic acids (trans-6,8,9,11 18:1 fatty acids, TOAs), a major component of trans fatty acid, in human tissue samples, and then determined the TOAs level in the placenta. Oleic acid (OA) (C18:1(9c)) was measured by isotope dilution gas chromatography-mass spectrometry, and the TOAs level was subsequently calculated based on the ratio of the peak areas for TOAs and OA (TOAs/OA) in the mass chromatogram. Lipids were extracted from 28 human placentas at different gestational ages from 28 to 41 weeks, and the TOAs and OA levels were measured. In method validation, the limit of detection for elaidic acid (trans-9,18:1 fatty acid), a major component of TOAs, was 0.57 ng, and linearity of calibration ranging from 7.7 to 68.0 µg/g placenta for TOAs. In human placenta analysis, the TOAs level was significantly higher in term (n = 15, 40.2 ± 9.7 µg/g placenta) than in preterm placentas (n = 13, 18.9 ± 7.4 µg/g placenta) (p < 0.001), while OA levels were similar in term (n = 15, 863 ± 132 µg/g placenta) and preterm (n = 13, 743 ± 283 µg/g placenta) placentas (p = 0.15). TOAs accumulate in the placenta as pregnancy progresses and have a fate different from that of OA in vivo. To our knowledge, this is the first report of TOA quantification in human tissue samples. Copyright © 2017 John Wiley & Sons, Ltd.

Longitudinal impairment of lung function in school-age children with extremely low birth weights.

OBJECTIVES: To assess lung function and long-term respiratory outcomes in extremely low birth weight (ELBW) survivors. WORKING HYPOTHESIS: ELBW, especially with respiratory complications in the neonatal period, affects lung function at a later age. STUDY DESIGN: Longitudinal retrospective study. PATIENT-SUBJECT SELECTION: Lung function was evaluated in 89 ELBW survivors (at ages 8 and 12) with or without a history of bronchopulmonary dysplasia (BPD) or a bubbly/cystic lung appearance in the neonatal period. METHODOLOGY: FVC, FEV1 , FEF50 , and FEF75 were measured using spirometry. Two-way repeated-measures ANOVA was used to compare lung function and deterioration time course from 8 to 12 years of age. RESULTS: Lung function variables were significantly and positively correlated between 8 and 12 years: %FVC (R2 = 0.558), %FEV1 (R2 = 0.539), %FEF50 (R2 = 0.412), and %FEF75 (R2 = 0.429). Lung function values were lower than Japanese reference values, especially in children with a history of severe BPD or a bubbly/cystic appearance. %FEV1 and FEV1 /FVC ratio worsened from 8 to 12 years of age: 83.0 ± 17.0% versus 76.6 ± 17.8% (mean difference, 95%CI: -6.43, -9.10 to -3.75) and 84.0 ± 10.1% versus 78.2 ± 13.4% (mean difference, 95%CI: -5.82, -8.56 to -3.08), regardless of whether or not there was a history of neonatal respiratory disease. CONCLUSIONS: In ELBW survivors, the obstructive pattern of lung function impairment deteriorated from 8 to 12 years of age, independent of the presence of severe BPD or bubbly/cystic appearance in the neonatal period.

Safety of Bifidobacterium breve (BBG-01) in preterm infants.

BACKGROUND: Since 1982, viable cells of Bifidobacterium breve (BBG-01) have been used in pediatric patients for clinical conditions such as intractable infantile diarrhea, preterm status, and pediatric surgery. Although the efficacy of BBG-01 has been widely reported, adverse events related to the use of BBG-01 have been reported in very few cases. METHODS: In order to trace adverse events seen by 109 doctors in 88 medical institutions where BBG-01 was used, a questionnaire survey of the number of occurrences and details of each case was conducted. RESULTS: Eighty-six clinicians (70 institutions) responded to the questionnaire (response rate, 78.9%). Number of respondents according to department of diagnosis (no. BBG-01-treated infants) was as follows: pediatrics, 29 respondents (10 938 patients); premature and newborn medicine, 26 (10 677 patients); obstetrics and gynecology, 1 (1212 patients) and pediatric surgery, 22 (169 patients). More than 90% of the total BBG-01-treated patients (23 092 patients) were in the departments of premature and newborn medicine and pediatrics, and BBG-01 had been used mainly in preterm infants and children with intractable diarrhea. Adverse events occurred in two extremely premature infants with functional ileus due to starch aggregates as vehicle, and in two surgical neonates with bacteremia caused by B. breve genetically identical to BBG-01, and no serious adverse events with poor outcome were reported. CONCLUSION: Adverse events related to the use of BBG-01 have an extremely low incidence and are mild in severity, thus ensuring the superior safety of this preparation.

Risk factors associated with a decreased estimated glomerular filtration rate based on cystatin C levels in school-age children with extremely low birthweight.

AIM: A single centre retrospective cohort study was designed to investigate the estimated glomerular filtration rate (eGFR) in school-age children born with extremely low birthweight (ELBW) and to determine risk factors predictive of decreased eGFR. METHODS: We compared eGFR based on cystatin C (CysC-eGFR) between school-age children born with ELBW (ELBW group, n = 48; median gestational age: 26.9 weeks; median birthweight: 792 g) and children born at term (control group, n = 48). The ELBW group was then further divided into a decreased CysC-eGFR subgroup (eGFR <90 mL/min per 1.73 m2 , n = 20) and a normal CysC-eGFR subgroup (n = 28), and perinatal background factors were compared. RESULTS: The ELBW group showed a significantly lower CysC-eGFR compared with the control group (P < 0.001). Comparison between the decreased and normal CysC-eGFR subgroups in the ELBW group showed that children with lower birthweight, shorter gestational age, lower 5-min Apgar score, longer length of mechanical ventilation, lower weight gain in the first 11 weeks, chronic lung disease, and postnatal corticosteroid administration had significantly decreased CysC-eGFR. Multivariate logistic regression showed that a lower 5-min Apgar score was the only independent risk factor for decreased CysC-eGFR. CONCLUSIONS: CysC-eGFR might already be decreased at school age in children born with ELBW. Renal assessment in regular follow-up examinations is recommended.

Vulnerability of Purkinje Cells Generated from Spinocerebellar Ataxia Type 6 Patient-Derived iPSCs.

Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies. Patient-derived Purkinje cells exhibit increased levels of full-length Cav2.1 protein but decreased levels of its C-terminal fragment and downregulation of the transcriptional targets TAF1 and BTG1. We further demonstrate that SCA6 Purkinje cells exhibit thyroid hormone depletion-dependent degeneration, which can be suppressed by two compounds, thyroid releasing hormone and Riluzole. Thus, we have constructed an in vitro disease model recapitulating both ontogenesis and pathogenesis. This model may be useful for pathogenic investigation and drug screening.

SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.

Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.

Eye-Mouth Associated Movement in the Human Newborn and Very Young Infant.

BACKGROUND: The aim of this study is to demonstrate that goal-directed eye-mouth associated movement exists in the newborn and very young infant. METHODS: The participants were 17 healthy term newborns or very young infants whose ages at the time of the first examination ranged from 1 to 24 days. The examiner held the tip of an index finger 20 to 30 cm in front of a participant's mouth, then suddenly moved it directly toward the mouth. Thirteen of the participants were also examined with the examiner's palm as the visual stimulus. The response was judged to be positive if clear mouth opening was elicited as the fingertip or palm was approaching the mouth. RESULTS: In the examinations using a fingertip, the frequency of a positive response as to the total number of examinations in the different age groups within the first two months of life ranged between 43.9% and 48.8%, and precipitously decreased to 6.3% at two months of age. A positive response was not elicited from age three months. On the other hand, in the examinations using a palm, the frequency of a positive response was 5.0% in the newborns, and 6.7% in the infants aged between seven days and one month. A positive response was never obtained from two months of age. CONCLUSION: This study demonstrated that visually guided mouth opening toward an approaching target exists in the human newborn. The eye-mouth associated movement may be controlled through rudimentary but functional visuomotor circuits in the brain interconnecting different cortices.

Lethal hypophosphatasia successfully treated with enzyme replacement from day 1 after birth.

UNLABELLED: Hypophosphatasia (HPP) is a rare metabolic bone disease caused by loss-of-function mutations in the gene ALPL encoding the tissue nonspecific alkaline phosphatase (TNSALP). There is a broad range of severity in the phenotype of HPP, and the most severe form exhibits perinatal lethality without mineralization of the skeleton. Here, we describe a female infant with perinatal lethal HPP diagnosed in utero. She was treated with a recombinant ALP (asfotase alfa) as an enzyme replacement therapy (ERT), which started from 1 day after birth. She required invasive ventilation immediately upon birth and demonstrated severe hypomineralization of whole body bone. Severe respiratory insufficiency was controlled by intensive respiratory care with high-frequency oscillation ventilation and nitric oxide inhalation and deep sedation just after birth. Bone mineralization improved with treatment; improvements were visible by 3 weeks of age and continued with treatment. Serum calcium levels decreased following treatment, resulting in hypocalcemia and convulsion, and calcium supplementation was required until 3 months of treatment. She was weaned from mechanical ventilation and has now survived more than 1 year. CONCLUSION: This case demonstrates the success of ERT in treating the severest HPP and highlights the importance of early diagnosis and intervention for these patients.

Major neonatal surgery: psychosocial consequence of the patient and mothers.

PURPOSE: Our previous studies of long-term QOL after major neonatal surgery revealed an unexpectedly high incidence of mental retardation as well as emotional and psychosocial problems, and the patients' QOL correlated with maternal QOL and post-traumatic stress disorder (PTSD). The main purpose of this study was to clarify the risk factors affecting long-standing maternal PTSD. MATERIALS AND METHODS: Sixty-eight patients, aged between 6 and 17years, and their mothers were enrolled in this study. The underlying diseases included congenital diaphragmatic hernia in 21, anorectal anomalies in 25 and esophageal atresia in 22. Psychoanalysts carried out intelligence tests, the Child Behavior Checklist and QOL evaluation in the patients. QOL was evaluated with WHOQOL26 and PTSD with IES-R questionnaires in their mothers. The mothers were divided into two groups; low- and high-risk groups according to PTSD score. RESULTS: Patient QOL scores correlated positively with maternal QOL (p<0.05) and negatively with maternal PTSD scores (p<0.05). There were significant differences in total number of hospital admissions (p<0.05), feeling of economic burden (p<0.05), and satisfaction with husband's help (p<0.01) between the two groups. CONCLUSION: Risk factors for maternal PTSD include repeated hospitalization, a feeling of economic burden, and lack of satisfaction with husband's help.

Pathological examination of the placenta in small for gestational age (SGA) children with or without postnatal catch-up growth.

BACKGROUND/OBJECTIVE: Approximately 10% of small for gestational age (SGA) infants fail to catch up. The relationship between postnatal growth and placental pathology in SGA infants remains unclear. Our aim was to assess the involvement of placental pathology in postnatal growth of SGA infants. METHODS: We retrospectively evaluated placental pathology and postnatal growth in single-pregnancy infants born after 37 gestational weeks in our institution, with both birth weight and length below -2 standard deviation scores (SDS) of the normal weight and length. "Catch-up" was defined as height reaching -2 SDS before the second birthday. Pathology of the placenta was classified into: abnormality due to maternal factors or fatal factors, villitis of unknown etiology (VUE), other abnormalities and no abnormality. RESULTS: Of the 33 084 infants, 142 met our criteria and 49 of them had analyzable data. The overall catch-up rate was 84%. Catch-up growth took place in all infants with no placental abnormality and only 57% of infants with abnormality due to fatal factors. There was no significant relationship between catch-up rate and other factors. CONCLUSION: Placental pathology is associated with postnatal growth in SGA children born at term. Placental abnormality due to fetal factors is related to poor catch-up rate.

Perinatal factors associated with long-term respiratory sequelae in extremely low birthweight infants.

OBJECTIVE: To assess lung function at 8 years old in extremely low birthweight (ELBW) survivors and to identify perinatal determinants associated with impaired lung function. DESIGN: Retrospective cohort study. SETTING: Level III neonatal intensive care unit. PATIENTS: ELBW survivors born in 1990-2004 with available spirometry at 8 years old were studied. Children were excluded if they had a Wechsler Intelligence Scale for Children Third Edition full IQ <70. MAIN OUTCOME MEASURES: Multivariate logistic regression analysis was used to identify perinatal determinants associated with airway obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <80%) at school age and the predictive power of potential determinants. Potential risk factors and predictors assessed in this study were gestational age, birth weight, small for gestational age, sex, chorioamnionitis, premature rupture of membranes, antenatal steroids, surfactant administration, respiratory distress syndrome, postnatal steroids, severe bronchopulmonary dysplasia and bubbly/cystic appearances of the lungs by X-ray during the neonatal period. RESULTS: Of 656 ELBW survivors, 301 (45.9%) had attended a school-age follow-up at 8 years old. A total of 201 eligible children completed the lung function test. Bubbly/cystic appearance of the lungs (OR 4.84, 95% CI 1.26 to 18.70) was associated with a low FEV1/FVC ratio. Children with bubbly/cystic appearance had characteristics of immaturity and intrauterine inflammation. CONCLUSIONS: Within a cohort of ELBW infants, a bubbly/cystic appearance of the lungs in the neonatal period was the strongest determinant of a low FEV1/FVC ratio at school age.