Antenatal Corticosteroid Exposure is Associated with Childhood Mental Disorders in Late Preterm and Term Infants.

OBJECTIVES: To study the association between antenatal corticosteroids treatment and childhood mental disorders in infants born at different gestational ages, and to investigate the effect of different administration timing. STUDY DESIGN: This population-based cohort study used data from the Taiwan National Health Insurance Research Database. All singleton live births born between 2004 and 2010 were enrolled and followed up for at least 6 years. The primary outcome was any childhood mental disorder. Secondary outcomes included 7 specific subgroups of mental disorders. RESULTS: A total of 1 163 443 singleton infants were included in the analysis, and 16 847 (1.45%) infants were exposed to antenatal corticosteroid treatment. Children exposed to antenatal corticosteroids were found to have a higher risk of developing childhood mental disorders in the entire cohort (hazard ratio [HR], 1.13; 95% CI, 1.08-1.18), the term group (HR, 1.11; 95% CI, 1.05-1.16), and the late-preterm group (HR, 1.15; 95% CI, 1.06-1.25). The administration of corticosteroids in the early stage of pregnancy (<28 weeks of gestation) significantly increased the risk of childhood mental disorders (HR, 1.22; 95% CI, 1.14-1.31). CONCLUSIONS: Exposure to antenatal corticosteroid treatment increases the cumulative risk of childhood mental disorders and attention deficit hyperactivity disorders, both in term and late preterm infants. The administration of corticosteroids in the early stage of pregnancy tends to increase the risk of mental disorders.

Maternal risk factors for preterm birth in Taiwan, a nationwide population-based cohort study.

BACKGROUND: The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective. METHODS: This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan's Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease. RESULTS: A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth. CONCLUSION: The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth.

Impact of COVID-19 pandemic on neurodevelopmental outcomes of premature infants: a retrospective national cohort study.

OBJECTIVE: To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic. DESIGN: Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group. SETTING: Nationwide cohort study. PATIENTS: Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database. INTERVENTIONS: Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic. MAIN OUTCOME MEASURES: Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model. RESULTS: Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p<0.001), and motor composite at corrected ages of 12 months (beta=1.680; 95% CI, 0.34 to 3.02; p=0.014). GEE analysis showed that infants who had grown during the pandemic achieved higher scores in cognitive composite (beta=1.416; 95% CI, 0.36 to 2.48; p=0.009). CONCLUSION: Premature infants in Taiwan who developed during the pandemic showed better neurodevelopment compared with those born before the pandemic.

Case Report: Neurally adjusted ventilatory assist as an effective rescue treatment for pulmonary interstitial emphysema in extremely low birth weight infants.

Pulmonary interstitial emphysema (PIE) is a complication observed in extremely low birth weight (ELBW) infants on mechanical ventilation. Despite various proposed therapeutic interventions, the success rates have shown inconsistency. Neurally adjusted ventilatory assist (NAVA) stands out as a novel respiratory support mode, offering lower pressure and tidal volume in comparison to conventional ventilation methods. In this case report, we present five ELBW infants with refractory PIE who were transitioned to NAVA ventilation. Following the switch to NAVA, all cases of PIE gradually resolved. In contrast to traditional modes, NAVA provided respiratory support with significantly lower fraction of inspired oxygen, reduced peak inspiratory pressure, diminished mean airway pressure, and decreased tidal volume within 7 days of NAVA utilization (p = 0.042, 0.043, 0.043, and 0.042, respectively). Consequently, we propose that NAVA could serve as a valuable rescue treatment for ELBW infants with PIE.

Decreased Incidence of Intraventricular Hemorrhage in Extremely Low Birth Weight Infants Using Customized Circulatory Management to Evaluate the Hemodynamic Change of Patent Ductus Arteriosus.

Background: In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants. Methods: We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia. Results: A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 (p = 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration (p = 0.017). Conclusion: The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective "early target therapy" for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications.

Correction: Post-discharge body weight and neurodevelopmental outcomes among very low birth weight infants in Taiwan: A nationwide cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0192574.].

Correction: Post-discharge body weight and neurodevelopmental outcomes among very low birth weight infants in Taiwan: A nationwide cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0192574.].

Post-discharge body weight and neurodevelopmental outcomes among very low birth weight infants in Taiwan: A nationwide cohort study.

BACKGROUND: Premature infants are at high risk for developmental delay and cognitive dysfunction. Besides medical conditions, growth restriction is regarded as an important risk factor for cognitive and neurodevelopmental dysfunction throughout childhood and adolescence and even into adulthood. In this study, we analyzed the relationship between post-discharge body weight and psychomotor development using a nationwide dataset. MATERIALS AND METHODS: This was a nationwide cohort study conducted in Taiwan. Total of 1791 premature infants born between 2007 and 2011 with a birth weight of less than 1500 g were enrolled into this multi-center study. The data were obtained from the Taiwan Premature Infant Developmental Collaborative Study Group. The growth and neurodevelopmental evaluations were performed at corrected ages of 6, 12 and 24 months. Post-discharge failure to thrive was defined as a body weight below the 3rd percentile of the standard growth curve for Taiwanese children by the corrected age. RESULTS: The prevalence of failure to thrive was 15.8%, 16.9%, and 12.0% at corrected ages of 6, 12, and 24 months, respectively. At corrected ages of 24 months, 12.9% had low Mental Developmental Index (MDI) scores (MDI<70), 17.8% had low Psychomotor Developmental Index (PDI) scores (PDI<70), 12.7% had cerebral palsy, and 29.5% had neurodevelopmental impairment. Post-discharge failure to thrive was significantly associated with poor neurodevelopmental outcomes. After controlling for potential confounding factors (small for gestational age, extra-uterine growth retardation at discharge, cerebral palsy, gender, mild intraventricular hemorrhage, persistent pulmonary hypertension of newborn, respiratory distress syndrome, chronic lung disease, hemodynamic significant patent ductus arteriosus, necrotizing enterocolitis, surfactant use and indomethacin use), post-discharge failure to thrive remained a risk factor. CONCLUSION: This observational study observed the association between lower body weight at corrected age of 6, 12, and 24 months and poor neurodevelopmental outcomes among VLBW premature infants. There are many adverse factors which can influence the neurodevelopment in NICU care. More studies are needed to elucidate the causal relationship.

Characterization of a recombinant d-allulose 3-epimerase from Agrobacterium sp. ATCC 31749 and identification of an important interfacial residue.

d-Allulose 3-epimerase (DAEase) catalyzes the epimerization between d-fructose and d-allulose. We had PCR-cloned and overexpressed the gene encoding Agrobacterium sp. ATCC 31749 DAEase (AsDAEase) in Escherichia coli. A high yield of active AsDAEase, 35,300U/L or 1350U/g of wet cells, was acquired with isopropyl ß-d-1-thiogalactopyranoside induction at 20°C for 20h. Although only six residues including residue 234 located in tetrameric interface are different between AsDAEase and A. tumefaciens DAEase (AtDAEase), the specific activity of purified AsDAEase is much larger than that of AtDAEase. The optimal pHs and optimal temperatures of the purified recombinant AsDAEase are 7.5-8.0 and 55-60°C, respectively. The half-life of the enzyme is 267min at 55°C in the presence of 0.1mM Co2+, and the equilibrium ratio between d-allulose and d-fructose is 30:70 at 55°C. Besides characterizing AsDAEase, mutation N234D was constructed to assess its influence on activity. The specific activity of the purified N234D AsDAEase is only 25.5% of wild-type's activity, suggesting residue N234 is an important interfacial residue which substantially affects enzyme activity. The high specific activity and high expression yield of AsDAEase suggest its prospect to be applied in d-allulose production.