Association between mean airway pressure during high-frequency oscillatory ventilation and pulmonary air leak in extremely preterm infants during the first week of life.

Background: While positive pressure ventilation has been considered an important contributing factor associated with pulmonary air leaks, studies examining the association between specific ventilatory settings during acute-phase high-frequency oscillatory ventilation (HFOV) and pulmonary air leaks among extremely preterm infants are limited. Methods: This was a single-center retrospective cohort study conducted at an institution that primarily used HFOV after intubation in extremely preterm infants. We analyzed data from extremely preterm infants born between 2010 and 2021. The primary outcome was pulmonary air leakage during the first 7 days of life. The exposure variable was the maximum mean airway pressure (MAP) on HFOV during the first 7 days of life or before the onset of pulmonary air leaks. Maximum MAP was categorized into three groups: low (7-10 cmH2O), moderate (11-12 cmH2O), and high (13-15 cmH2O) MAP categories. We conducted robust Poisson regression analyses after adjustment for perinatal confounders, using the low MAP category as the reference. Results: The cohort included 171 infants (low MAP, 123; moderate MAP, 27; and high MAP, 21). The median (interquartile range) gestational age and birth weight were 25.7 (24.3-26.7), 25.7 (24.9-26.9), and 25.3 (24.3-26.6) weeks and 760 (612-878), 756 (648-962), and 734 (578-922) g for infants in the low, moderate, and high MAP categories, respectively. Compared to infants in the low MAP category, those in the high MAP category had a higher incidence of pulmonary air leaks (4.1% vs. 33.3%; adjusted risk ratio, 5.4; 95% confidence interval, 1.6-18.5). In contrast, there was no clear difference in the risk of pulmonary air leaks between the moderate and low MAP categories (3.7% vs. 4.1%; adjusted risk ratio, 0.9; 95% confidence interval, 0.1-6.1). Conclusion: Extremely preterm infants requiring high MAP (≥13 cmH2O) in acute-phase HFOV had a higher risk of pulmonary air leak during the first 7 days of life.

Delivery room intubation and neurodevelopment among extremely preterm infants.

BACKGROUND: The impact of delivery room intubation (DRI) on neurodevelopment in extremely preterm infants remains unclear. METHODS: We retrospectively analyzed data for infants born at 24-27 gestational weeks between 2003 and 2018. The primary outcome was neurodevelopmental impairment (NDI), defined as cerebral palsy or hearing, visual, or cognitive impairment at age 3 years. Secondary outcomes were NDI components and death before and after discharge from the neonatal intensive care unit. We conducted robust Poisson regression analyses, adjusting for perinatal confounders. RESULTS: The full cohort included 4397 infants with NDI data, of whom 3703 were intubated in the delivery room and 694 were not intubated in the delivery room. The mean gestational age and birth weight were 26.0 ± 1.1 weeks and 778 ± 184 g for infants with DRI and 26.6 ± 1.0 weeks and 873 ± 184 g for infants without DRI. Compared with infants without DRI, those with DRI had a higher risk for NDI (32.4% vs. 23.3%; adjusted risk ratio 1.18, 95% confidence interval: 1.01-1.37). There were no differences in secondary outcomes between infants with and without DRI. CONCLUSIONS: DRI was associated with an increased risk for NDI at age 3 years among extremely preterm infants. IMPACT: Few studies have examined the impact of delivery room intubation on neurodevelopment in infants born extremely preterm, and the results have been inconsistent. A total of 4397 infants born at 24-27 gestational weeks who had neurodevelopmental data at age 3 years were included in the present study. The present study found that delivery room intubation was associated with an increased risk for neurodevelopmental impairment at age 3 years among extremely preterm infants.

Delivery room intubation and severe intraventricular hemorrhage in extremely preterm infants without low Apgar scores: A Japanese retrospective cohort study.

The purpose of this study was to assess the associations between delivery room intubation (DRI) and severe intraventricular hemorrhage (IVH), as well as other neonatal outcomes, among extremely preterm infants without low Apgar scores using data from a large-scale neonatal registry data in Japan. We analyzed data for infants born at 24-27 gestational weeks between 2003 and 2019 in Japan using robust Poisson regression. Infants with low Apgar scores (≤ 1 at 1 min or ≤ 3 at 5 min) were excluded. The primary outcome was severe IVH. Secondary outcomes were other neonatal morbidities and mortality. The full cohort included 16,081 infants (intubation cohort, 13,367; no intubation cohort, 2714). The rate of DRI increased over time (78.6%, 2003-2008; 83.4%, 2009-2014; 87.8%, 2015-2019), while the rate of severe IVH decreased (7.1%, 2003-2008; 5.7%, 2009-2014; 5.3%, 2015-2019). Infants with DRI had a higher risk of severe IVH than those without DRI (6.8% vs. 2.3%; adjusted risk ratio, 1.86; 95% confidence interval, 1.33-2.58). The results did not change substantially when stratified by gestational age. Despite conflicting changes over time in DRI and severe IVH, DRI was associated with an increased risk of severe IVH among extremely preterm infants in Japan.

Association between infant breastfeeding practices and timing of peak height velocity: A nationwide longitudinal survey in Japan.

BACKGROUND: Several studies have discovered an association between infant feeding practices and puberty timing; however, most have involved female cohorts. We investigated the association between infant feeding practices and the timing of peak height velocity in boys and girls. METHODS: Data on infant feeding methods and anthropometric measurements were collected from a nationwide Japanese birth cohort study. The age at peak height velocity (APV, years) was estimated and compared. Subsequently, the effects of breastfeeding duration were analyzed. RESULTS: Of the 13,074 eligible participants, 650, 9455, and 2969 were formula-, mixed-, and exclusively breastfed, respectively. Among girls, the mean APV was significantly later in the mixed-fed (standardized regression coefficient (ß): 0.094, 95% confidence interval (CI): 0.004-0.180) and exclusively breastfed (ß: 0.150, 95% CI: 0.056-0.250) groups than in the formula-fed group. Among boys, the mean APV was not significantly different among the three groups; however, a sensitivity analysis that excluded preterm birth revealed more significantly delayed APV in the breastfed-only group compared to the formula-fed group. Furthermore, a multiple linear regression model revealed that a longer breastfeeding period was associated with later APV. CONCLUSIONS: Infant breastfeeding practices can affect the timing of peak height velocity in both boys and girls. IMPACT: Several studies have discovered an association between infant feeding practices and puberty timing; however, most have involved female cohorts. Age at peak height velocity, derived from longitudinal height measurements, is a useful marker of secondary sexual maturity milestones in boys and girls. A Japanese birth cohort study revealed that breastfed children had a later age at peak height velocity than their formula-fed counterparts; this was more prominent among girls than boys. Furthermore, a duration-effect relationship was observed, where longer breastfeeding duration was associated with a later age at peak height velocity.

Neonatal sepsis and Kawasaki disease.

The purpose of this study is to clarify the relationship between neonatal sepsis and future development of Kawasaki disease (KD). We analyzed data from the National Hospital Organization Neonatal Intensive Care Unit (NHO-NICU) registry study in Japan. Participants in this study were children with a history of hospitalization in the NICU at the participating institutions from 2010 to 2014. A questionnaire was administered at age 3 years to obtain information about the patient's history of KD. There were 8275 infants who were eligible for this study. At 3 years of age, parents of 2161 children responded to the follow-up survey (follow-up rate, 26.1%). Multivariate logistic regression analysis adjusted for preterm birth, sex, use of antibiotics in the NICU, parity, and maternal smoking showed that children with neonatal sepsis were more likely to have a history of KD at 3 years of age (adjusted odds ratio [aOR]: 11.67, 95% confidence interval [CI]: 2.84-47.96). CONCLUSIONS: Among infants admitted to the NICU, neonatal sepsis might be associated with development of KD later in life. Further large studies are needed to elucidate the relationship between neonatal infections and KD development. WHAT IS KNOWN: • Preterm birth is known to be a risk factor for Kawasaki disease. •It is not yet known which factors related to preterm birth increase the risk of developing Kawasaki disease. WHAT IS NEW: •Neonatal sepsis is associated with an increased risk of subsequent development of Kawasaki disease. •Antibiotic use in the neonatal intensive care unit may also be an independent risk factor for subsequent development of Kawasaki disease.

Early childhood exposure to maternal smoking and behavioral development.

We examined the association between early childhood exposure to maternal smoking and behavioral issues at 8 years old using a large nationwide population-based longitudinal survey in Japan that began in 2001. We included 46,737 children with information about maternal smoking taken from the 6-month survey. We used logistic regression analysis to examine the hypothesis. Early childhood exposure to maternal smoking increased the risk of behavioral problems related to attention and aggressive or disruptive behavior. The adjusted odds ratios (95% confidence intervals) were 1.37 (1.22-1.54) for inability to wait their turn during play and 1.40 (1.27-1.55) for destroying toys and, compared with children of nonsmoking mothers. Children of mothers who were heavy smokers were more likely to develop behavioral problems than others. Stopping early childhood exposure to maternal exposure can protect children's neurodevelopment.

Preterm birth and Kawasaki disease: a nationwide Japanese population-based study.

BACKGROUND: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. METHODS: We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. RESULTS: In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. CONCLUSIONS: Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. IMPACT: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.

Sports participation and preterm birth: a nationwide birth cohort in Japan.

BACKGROUND: Children born preterm may be less physically active than children born term because of neurocognitive problems, reduced lung function, and poor physical fitness. We evaluated sports participation of children and adolescents who had been born preterm (<37 weeks) and early term (37-38 weeks) in 2001. METHODS: Data from a nationwide longitudinal survey (n = 47,015, including 2375 children born preterm) were analyzed. As indicators of sports participation, we used responses to questions about participation in sports clubs at 7 and 10 years old and in extracurricular school sports at 15 years old. RESULTS: Children born very preterm (25-31 weeks) and moderately to late preterm (32-36 weeks) were less likely to participate in sports clubs at 7, 10, and 15 years old than children born full term (39-41 weeks). Compared with children born full term, the adjusted risk ratios for participation in extracurricular school sports at 15 years old were 0.86 (95% confidence interval: 0.75-0.98) for children born very preterm, 0.92 (0.88-0.97) for children born moderately to late preterm, and 1.00 (0.98-1.02) for children born early term. CONCLUSIONS: Our findings suggest that preterm birth is associated with less participation in organized sports during childhood and adolescence than full-term birth. IMPACT: Research investigating associations between preterm birth and physical activity among children born in the 2000s is limited. This study shows that preterm birth was associated with less participation in organized sports during childhood and adolescence than full-term birth, especially in boys, and the participation in organized sports of children born preterm decreased as gestation shortened. During childhood, boys born early term were also less likely to participate in organized sports than boys born full term, suggesting a continuum with preterm births. These findings offer important additional insights into the limited evidence available for predicting future health outcomes for preterm infants.

Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan.

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.

The Optimal Prepregnancy Body Mass Index for Lactation in Japanese Women with Neonatal Separation as Analyzed by a Differential Equation.

We used a differential equation to identify the biological relationship between the maternal prepregnancy body mass index (BMI) and lactation on postpartum day 4 in Japanese women with neonatal separation. This retro-spective observational study included 252 mothers (135 primiparas, 117 multiparas) whose singleton neonates were admitted to a neonatal ICU. We formulated hypotheses based on breast anatomy to analyze the relation-ship between the expressed milk obtained on postpartum day 4 and the maternal prepregnancy BMI with the following differential equation: y'(x) = k y(x)/x, where k is the constant, x is the prepregnancy BMI, and y is the expressed milk volume. The formula was then obtained as y(x) = axk, where a is the constant. The Akaike information criterion (AIC) was used to estimate the regression equation with the maximum likelihood for primiparas and multiparas. The best criteria for BMI determined by the AIC were 20.89 kg/m2 in primiparas and 20.19 kg/m2 in multiparas. These were the optimal BMI values for lactation, coinciding with the median prepregnancy BMI in the study population (20.78 kg/m2 in primiparas and 20.06 kg/m2 in multiparas). The formula based on biomathematics might help establish the biological relationship between prepregnancy BMI and breastmilk volume.

Exclusively Breastfeeding Modifies the Adverse Association of Late Preterm Birth and Gastrointestinal Infection: A Nationwide Birth Cohort Study.

Introduction: Late preterm infants (LPIs) are at greater risk for short- and long-term morbidity compared with term infants. However, little is known about whether breastfeeding can reduce the adverse effect of late preterm (LP) birth on various diseases. Therefore, we examined the association of LP birth with the risk of hospitalizations from 6 to 18 months of age, then explored the possible modification of this effect by breastfeeding. Materials and Methods: Data were extracted from a nationwide population-based longitudinal survey in Japan. We restricted our analysis to term and LPIs with information on hospitalization (n = 31,578). Multivariate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated to evaluate the association between LP birth and hospitalization using term birth as the reference. We then examined whether breastfeeding status modified the potential adverse effects of LP birth on each health outcome. Results: LPIs were more likely to be hospitalized for all-cause (aOR, 1.58; 95% CI, 1.35-1.86), respiratory (aOR, 1.52; 95% CI, 1.21-1.92) and gastrointestinal infections (aOR, 1.73; 95% CI, 1.14-2.62) than term infants. While LPIs had a higher risk of hospitalization for all-cause and respiratory infection regardless of breastfeeding status, we did not observe an increased risk of hospitalization for gastrointestinal infection among the exclusively breastfed LPIs, in contrast with increased risk among the non-exclusively breastfed LPIs. Conclusions: We found that LPIs had a higher risk of all-cause and cause-specific hospitalization compared with term infants. Moreover, exclusive breastfeeding probably reduced the adverse effect of LP birth on gastrointestinal infection.

Breastfeeding and risk of food allergy: A nationwide birth cohort in Japan.

BACKGROUND: Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. METHODS: This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6-18 months and age 6-66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. RESULTS: Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6-66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6-66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. CONCLUSIONS: Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy.

Altered neural basis of self-reflective processing in schizophrenia: An fMRI study.

BACKGROUND: Impaired self-awareness has often been described in schizophrenia. Recent neuroimaging studies examining the self-reflection processes in schizophrenia have produced inconsistent results. METHOD: We examined the self-reflective neural network using self- and other-evaluation tasks in schizophrenia. Fifteen schizophrenia patients and fifteen age- and sex-matched healthy subjects underwent functional magnetic resonance imaging. Subjects were required to decide whether the sentence described their own personal trait (self-evaluation) and that of their close friends (other-evaluation). RESULTS: Unlike normal control subjects, the schizophrenia patients did not have greater activation of the left posterior cingulate gyrus and hippocampus during self-evaluation than during other-evaluation. On the other hand, the schizophrenia patients had higher activation of the right superior frontal and right supramarginal gyri during self-evaluation than control subjects. Only the patient group exhibited hyperactivation in the left hippocampus and right external capsule associated with the other-evaluation task. CONCLUSIONS: These findings provide evidence for an altered neural basis of self-reflective processing, which may underlie the self-awareness deficits in schizophrenia.

Catch-up growth and behavioral development among preterm, small-for-gestational-age children: A nationwide Japanese population-based study.

OBJECTIVE: To examine the relationship between the catch-up growth of preterm, SGA children and their behavioral development. METHODS: We analyzed data from a large Japanese, nationwide, population-based, longitudinal survey that started in 2001. We restricted the study participants to preterm children with information on height at 2 years of age (n = 1667). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age above -2.0 standard deviations for chronological age. We then used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations of SGA/catch-up status with neurobehavioral development both at 5.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. RESULTS: Twenty-six percent of preterm SGA infants failed to catch up. SGA children without catch-up growth were more likely to be unable to listen without fidgeting (OR 2.51, 95% CI: 1.06-5.93) and unable to focus on one task (OR 2.66, 95% CI: 1.09-6.48) compared with non-SGA children at 5.5 years of age. Furthermore, SGA children without catch-up growth were at significant risk for inattention at 8 years of age. CONCLUSIONS: SGA infants with poor postnatal growth were at risk for attention problems throughout preschool-age to school-age among preterm infants. Early detection and intervention for attention problems among these infants is warranted.

Catch-Up Growth and Neurobehavioral Development among Full-Term, Small-for-Gestational-Age Children: A Nationwide Japanese Population-Based Study.

OBJECTIVE: To examine the relationship between catch-up growth of full-term, small for gestational age (SGA) children and their neurobehavioral development. STUDY DESIGN: Data were obtained from a population-based nationwide Japanese longitudinal survey that started in 2001. Study participants were full-term children with information on height at 2 years of age (n = 32 533). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age of more than -2.0 standard deviations for chronological age. Logistic regression analyses were used to estimate ORs and 95% CIs for the associations of SGA and catch-up growth status with neurobehavioral development at 2.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. RESULTS: Fifteen percent of term SGA infants failed to catch up in height. At 2.5 years of age, SGA children without catch-up growth were more likely to be unable to climb stairs (OR, 10.42; 95% CI, 5.55-19.56) and unable to compose a 2-word sentence (OR, 3.58; 95% CI, 1.81-7.08) compared with children with normal growth at birth. Furthermore, SGA children without catch-up growth were at increased risk for aggressive behaviors (OR, 3.85; 95% CI, 1.19-12.47) at 8 years of age. CONCLUSIONS: Continuous follow-up for full-term SGA infants with failure of catch-up growth or poor postnatal growth may be beneficial for early detection and intervention for behavioral problems.

Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia.

AIM: Enlarged pituitary gland has been reported in schizophrenia, possibly reflecting hypothalamic-pituitary-adrenal hyperactivity. The aim of the present study was to examine whether individuals at risk of psychosis also have similar changes. METHODS: Magnetic resonance imaging was used to examine the pituitary volume in 22 individuals with at-risk mental state (ARMS; 11 male, 11 female), 64 first-episode patients with schizophrenia (FESz; 37 male, 27 female), and 86 healthy controls. The control subjects were divided into age- and gender-matched controls for ARMS (11 male, 11 female) and FESz (37 male, 27 female). RESULTS: Both the ARMS and FESz groups had a larger pituitary volume compared with matched controls, but no difference was found between the ARMS and FESz subjects. There was no association between the pituitary volume and clinical variables (symptommeasures at scanning, daily dosage or duration of antipsychotic medication) in either clinical group. The pituitary volume did not differ significantly between the ARMS individuals who later developed schizophrenia (n = 5) and those who did not (n = 17). The pituitary volume was larger in women than in men for all diagnostic groups. CONCLUSION: The finding of increased pituitary volume in both ARMS and FESz subjects may reflect a common vulnerability to stress in early psychosis. Further work in a larger ARMS sample is required to examine the possible relationship between pituitary volume and emergence of psychosis.

Longitudinal MRI study of the midline brain regions in first-episode schizophrenia.

This magnetic resonance imaging (MRI) study investigated the prevalence and size of the adhesio interthalamica (AI) and cavum septi pellucidi (CSP) in 64 first-episode schizophrenia patients and 64 controls, of whom longitudinal data were available for 20 patients and 21 controls. The AI was shorter in the patients and showed longitudinal decline in both groups; there was also a trend for AI atrophy to correlate with negative symptoms. The CSP showed no group difference. These results suggest a role for the AI as a possible neurodevelopmental marker of schizophrenia.

Gray matter changes in subjects at high risk for developing psychosis and first-episode schizophrenia: a voxel-based structural MRI study.

OBJECTIVES: The aim of the present study was to use a voxel-based magnetic resonance imaging method to investigate the neuroanatomical characteristics in subjects at high risk of developing psychosis compared with those of healthy controls and first-episode schizophrenia patients. METHODS: This study included 14 subjects with at-risk mental state (ARMS), 34 patients with first-episode schizophrenia, and 51 healthy controls. We used voxel-based morphometry with the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra tools to investigate the whole-brain difference in gray matter volume among the three groups. RESULTS: Compared with the healthy controls, the schizophrenia patients showed significant gray matter reduction in the left anterior cingulate gyrus. There was no significant difference in the gray matter volume between the ARMS and other groups. CONCLUSION: The present study suggests that alteration of the anterior cingulate gyrus may be associated with development of frank psychosis. Further studies with a larger ARMS subjects would be required to examine the potential role of neuroimaging methods in the prediction of future transition into psychosis.