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Symptomatic patent ductus arteriosus (sPDA) is common among preterm infants, and can lead to several complications. This is particularly true for extremely preterm infants, as closure of the ductus arteriosus using cyclooxygenase inhibitors is often difficult. A recent study using a preterm sheep model showed that intimal thickening—required for anatomical closure of the ductus arteriosus—is less developed in twins than in singletons. Therefore, this study primarily aimed to prove that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of extremely preterm singletons. Its secondary aim was to assess whether the resistance against cyclooxygenase inhibitors differed according to chorionicity. In this retrospective case–control study, medical records of 162 extremely preterm infants (gestational age < 28 weeks) were reviewed, and the treatment course of sPDA was subsequently compared between singletons ( n  = 131) and twins ( n  = 31). The median indomethacin doses for sPDA and the necessity for surgical ligation were significantly higher in twins than in singletons (5 vs 2 [ p  < 0.001] and 42% vs 21% [ p  = 0.018], respectively). No significant differences in sPDA treatment, including the number of indomethacin doses and the necessity for surgical ligation, were observed between monochorionic diamniotic and dichorionic diamniotic twins. This study confirms that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of singletons. However, there was no significant difference in sPDA treatment by chorionicity.

Aims This study investigated the association between maternal age and early and late gestational diabetes mellitus (GDM). Methods In total, 72,270 pregnant women were included in this prospective birth cohort study. Associations between maternal age and early GDM (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were evaluated using a multinomial logistic regression model with possible confounding factors. The reference category was maternal age of 30–34.9 years. Results Higher maternal age was associated with higher odds of early and late GDM (P‐value for trend <0.0001 and <0.0001, respectively). The adjusted odds ratios (aORs) for early GDM with maternal age of 35–39.9 years and ≥40 were 1.399 (95% confidence interval [CI]: 1.134–1.725) and 2.494 (95% CI: 1.828–3.402), respectively. The aORs for late GDM with maternal age of 35–39 years and ≥40 were 1.603 (95% CI: 1.384–1.857) and 2.276 (95% CI: 1.798–2.881), respectively. Conclusions Higher maternal age was associated with an increased risk of GDM regardless of when GDM was diagnosed. The association between maternal age and early GDM was similar to that between maternal age and late GDM. Higher maternal age was associated with an increased risk of GDM regardless of when GDM was diagnosed. The association between maternal age and early GDM was similar to that between maternal age and late GDM.

Functional constipation is the most common gastrointestinal disorder during childhood. Oral stimulation (mastication and toothbrushing) reportedly improves bowel movements, but the association between daily toothbrushing behavior and functional constipation remains unknown. Data (n = 83,660) from fetal records (n = 104,059) in the Japan Environment and Children’s Study, an ongoing prospective birth cohort, were analyzed to investigate the impact of daily toothbrushing frequency on functional constipation during childhood, using ROME III diagnostic criteria. After multiple imputations of data acquired from self-reported questionnaires, a multivariable binomial logistic regression analysis was used with adjustments for several maternal and child-related variables. Functional constipation was observed in 10,123 (12.1%) and 8,820 (10.5%) participants at 3 and 4 years postpartum, respectively. Using the appropriate frequency of daily toothbrushing (twice or more) as a reference, the odds of functional constipation increased with decreasing daily toothbrushing frequency after covariate adjustments involving daily feeding frequency. The adjusted odds ratio (OR) for functional constipation in participants without daily toothbrushing behavior (less than once a day) at 4 years postpartum was 1.87 (95% confidence interval [CI] 1.34–2.61). Similarly, the adjusted OR (95% CI) for chronic functional constipation (at both 3 and 4 years postpartum) in participants without daily toothbrushing behavior (less than once a day) at 2 years postpartum was 1.62 (1.14–2.31). Functional constipation during childhood was associated with decreased daily toothbrushing frequency. Although the underlying mechanism of daily toothbrushing behavior in prompting bowel movements remains unclear, it is a major basis of self-health management in children that plays an important role in managing functional constipation.

Background Dental caries is estimated to affect almost half of preschool children worldwide and is associated with low academic performance in school age and poor health in adulthood. Thus, the prevention of dental caries is an important issue that must be addressed. The objective of this study was to clarify the factors associated with early childhood dental caries (ECC) in 4-year-old children. Methods This study was part of an ongoing nationwide cohort study; the Japan Environment and Children’s Study. Approximately 100,000 expectant mothers were recruited from 15 Regional Centers between January 2011 and March 2014. Questionnaires were regularly administered to participating mothers. Data on the presence of ECC at 4 years of age, frequency of parental brushing, continuation of breastfeeding, parental smoking habits, and other factors considered to be related with development of ECC were obtained from the datasets released in October 2019 and April 2021. Then, the data were statistically analyzed. Results After excluding 25,990 cases due to missing data referring to the prevalence of ECC, 74,310 cases were analyzed. The logistic regression analysis revealed that occasional parental brushing (adjusted odds ratio (aOR) 1.33, 95% confidence interval (95% CI) 1.27–1.39) was associated with significantly increased odds for ECC when compared to routine parental brushing. In addition, extended breastfeeding (aOR 2.07, 95% CI 1.86–2.29), continued smoking of mothers (aOR 1.42, 95% CI 1.30–1.55), and continued smoking of fathers (aOR 1.25, 95% CI 1.20–1.31) were associated with increased odds for ECC. Conclusion Irregular parental brushing, extended breastfeeding, and parental smoking habits were found to be associated with increased odds for ECC in 4-year-old children.

Background/Objectives: Perinatal mental disorders are important health issues that affect both mothers and their children. The Mediterranean diet (MD) is one of the most well-recognized healthy dietary patterns worldwide. Recent evidence suggests that MD may prevent or reduce the risk of perinatal mental disorders. This study investigated the association between MD adherence during pregnancy and psychological distress in a large cohort of Japanese births. Methods: Data were obtained from 80,271 pregnant women who participated in the Japan Environment and Children’s Study. Adherence to the MD was assessed using three scoring methods: the Mediterranean Diet Score (MDS), relative Mediterranean Diet (rMED), and Mediterranean Diet Score for Pregnancy (PMDS). Psychological distress was defined as a score of ≥13 on the Kessler 6-item Psychological Distress Scale (K6). Modified Poisson regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (CIs). Population attributable fractions (PAFs) were calculated to quantify the proportion of psychological distress attributable to low MD adherence. Results: The adjusted RR for psychological distress in the low PMDS group was 1.17 (95% CI: 1.07, 1.28) compared with the high PMDS group. The adjusted PAF for low PMDS was 10.43% (95% CI: 4.81, 16.06). No statistically significant associations were detected between psychological distress and the MDS or rMED scores. Conclusions: This study suggests that high adherence to MD based on the PMDS during pregnancy may reduce the risk of psychological distress in Japanese women. Therefore, promoting MD during pregnancy could be a potential strategy for preventing perinatal mental disorders.

Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume. Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups. Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups. In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.

Sustained inflations (SI) are used with the initiation of ventilation at birth to rapidly recruit functional residual capacity and may decrease lung injury and the need for mechanical ventilation in preterm infants. However, a 20 second SI in surfactant-deficient preterm lambs caused an acute phase injury response without decreasing lung injury from subsequent mechanical ventilation. A 20 second SI at birth will decrease lung injury from mechanical ventilation in surfactant-treated preterm fetal lambs. The head and chest of fetal sheep at 126±1 day GA were exteriorized, with tracheostomy and removal of fetal lung fluid prior to treatment with surfactant (300 mg in 15 ml saline). Fetal lambs were randomized to one of four 15 minute interventions: 1) PEEP 8 cmH2O; 2) 20 sec SI at 40 cmH2O, then PEEP 8 cmH2O; 3) mechanical ventilation with 7 ml/kg tidal volume; or 4) 20 sec SI then mechanical ventilation at 7 ml/kg. Fetal lambs remained on placental support for the intervention and for 30 min after the intervention. SI recruited a mean volume of 6.8±0.8 mL/kg. SI did not alter respiratory physiology during mechanical ventilation. Heat shock protein (HSP) 70, HSP60, and total protein in lung fluid similarly increased in both ventilation groups. Modest pro-inflammatory cytokine and acute phase responses, with or without SI, were similar with ventilation. SI alone did not increase markers of injury. In surfactant treated fetal lambs, a 20 sec SI did not alter ventilation physiology or markers of lung injury from mechanical ventilation.

Mixture of starch and amorphous sodium polyborate (SPB) is found to show high flame retardancy, when its aqueous solution is deposited and dried on organic polymer materials such as polyethylene terephthalate (PET) nonwoven, rigid polyurethane (RPU) foam, and polypropylene (PP) nonwoven. The PET nonwoven (10 mm thickness) and the RPU foam (10 mm thickness) coated with the mixture endure the premixed flame of butane gas burner with length of 100 mm for more than 12 min. The PP nonwoven (0.7 mm thickness) endures the nonpremixed flame with length of 65 mm in the 45 degrees Meckel burner test for more than 2 min. The backside temperatures in the both tests remain below 130 °C. The thermal analyses and the SEM observation indicate the mechanism that the SPB foam promotes the carbonization of starch and that the carbonized layer together with the SPB foam insulate inside from oxygen and heat.

Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF), bronchoalveolar lavage fluid (BAL), right mainstem bronchi and peripheral lung tissue were evaluated for inflammation. Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used. Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

Nonwovens made of poly(ethylene terephthalate) (PET) and ethylene–vinyl alcohol copolymer (EVOH) are found to become highly fire resistant by treating with amorphous sodium polyborate (SPB). The fire-resistant nonwovens with 10-mm thickness show a gradual temperature increase up to 127 °C and no hole, when their back sides are fired with a gas burner for 12 min. The analysis using the EPMA and the DTA/TG indicates that the SPB foam promotes the formation of char (carbon) layer, and that the char layer together with the SPB foam insulates inside from the oxygen and the heat.