Caffeine and Bronchopulmonary dysplasia ：Clinical Benefits and Its Mechanisms

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease caused by a combination of prenatal and postnatal factors that leads to the disruption of lung development and abnormal repair, this is a condition that is commonly seen in premature infants. With the improvement of treatment technology, the survival rate of very early preterm infants has increased significantly compared with before, and the incidence of severe BPD has decreased, however, the prevalence of BPD has not decreased. The overall prevalence of BPD is 45%.The prevention of prematurity, the systematic use of non-aggressive ventilator measures, the avoidance of supra-physiological oxygen exposure, and the administration of diuretics, caffeine and vitamin A have all been shown to lead to a significant reduction in the risk of BPD development. A growing number of clinical studies have shown that caffeine not only prevents apnea, but also reduces the incidence of BPD. We review the clinical value of caffeine in the treatment of BPD and its potential mechanisms of action, include anti-inflammatory, antioxidant, anti-fibrotic, anti-apoptotic pathways, and the regulation of angiogenesis. Our aim was to provide a new theoretical basis for the clinical treatment of BPD.

Predictors of Developmental and Respiratory Outcomes Among Preterm Infants With Bronchopulmonary Dysplasia

Objectives: To examine the importance of perinatal and postnatal environmental factors on developmental and respiratory outcomes among preterm infants with bronchopulmonary dysplasia (BPD).Methods: Preterm infants (<32 weeks of gestation) born at a single tertiary medical center between 2012 and 2015 were included. Development was assessed at 12 months corrected age. Parents retrospectively completed a health and lifestyle questionnaire reviewing their child's health during the first 2 years of life. A linear regression model was applied to assess the effect of various perinatal and postnatal factors on development. A machine-learning algorithm was trained to assess factors affecting inhaler use.Results: Of 398 infants meeting the inclusion criteria, 208 qualified for the study: 152 (73.1%) with no BPD, 40 (19.2%) with mild BPD, and 16 (7.7%) with moderate-severe BPD. Those in the moderate-severe group were more likely to be male, have mothers who were less educated, and require longer ventilation periods and less time to regain birth weight. They were also more likely to have mothers with asthma/allergies and to have a parent who smoked. Those in the moderate-severe BPD group exhibited significantly lower developmental scores (85.2 ± 16.4) than the no-BPD group (99.3 ± 10.9) and the mild BPD group (97.8 ± 11.7, p < 0.008) as well as more frequent inhaler use (p = 0.0014) than those with no or mild BPD. In addition to perinatal factors, exposure to breast milk, income level and daycare attendance positively affected development. Exposure to cigarette smoke, allergies among family members and daycare attendance proved to be important factors in inhaler use frequency.Conclusions: Postnatal environmental factors are important in predicting and modifying early childhood outcomes among preterm infants.

P168 Pre and postnatal factors associated with periodic breathing in preterm infants

Introduction Immature cardio-respiratory control in preterm infants often manifests as periodic breathing (PB). A number of pre- and postnatal demographic and clinical factors, such as exposure to maternal smoking, respiratory support and medications may affect respiratory control. We aimed to identify specific factors affecting the frequency of PB in preterm infants before hospital discharge. Methods 32 healthy preterm infants (14M, 18F) born between 28–32 weeks of gestational age were studied for 2–3 hours with daytime polysomnography at 31–36 weeks (when they had been off respiratory support for ≥ 3 days). % sleep time spent in PB was calculated. Variables are reported as median (IQR) and were compared with Mann-Whitney U and Chi square tests, between infants who spent greater or less than the median time in PB. Results 29 infants (91%) exhibited at least one episode of PB. Median sleep time in PB was 9.6% (IQR 0.6, 15.6%). Infants with time in PB above the median spent fewer days on respiratory support (4.0 days (1.0, 7.5) vs 9.0 (6.5, 21.5) days, p=0.035), and were younger (post-menstrual age 33.8 (IQR 32.1, 34.5) vs 35.1 (IQR 32.4, 35.6) weeks, p= 0.039). Conclusions Of the large number of maternal and infant demographic and clinical variables examined, we found few associations with the time preterm infants spent in PB. Greater % time spent in PB was associated with earlier discontinuation of respiratory support, however larger studies are required to confirm these findings and to investigate if there are any long-term consequences.

Prenatal and postnatal determinants of stunting at age 0–11 months: A cross-sectional study in Indonesia

Background Childhood stunting remains the most challenging consequence of undernutrition because it is associated with suboptimal brain development and the subsequent increased risk of metabolic diseases and decreased earnings in adult life. The Sambas District in Indonesia has a high prevalence of stunting (28.4%), followed by underweight (25.5.%) and wasting (14.4%) among children, as well chronic energy deficiency (27%) and anemia (62%) among pregnant women. The present study sought to determine significant factors in childhood stunting with a focus on maternal and child nutrition and prenatal and postnatal determinants. Methods This prospective, repeat, cross-sectional study investigated factors associated with stunting among 559 infants age 0–11 months in Sambas District, Indonesia. Anthropometric measurements were performed by trained enumerators. Data from a 2016 survey of pregnant women and a 2017 survey on mothers and their children were used for postnatal data collection to quantify the prevalence of stunting at age 0–11 months. Using 20 potential predictors of stunting categorized by household characteristics, maternal characteristics, antenatal care services, and child characteristics, logistic regression analysis was conducted to assess the adjusted association between stunting and these factors. Results Of 559 children analyzed, 20.8% were stunted. In the model with low birth weight (LBW) as predictor for stunting, the odds of stunting increased significantly among children who weighed <2.500 g at birth; children who had diarrhea in the past 2 weeks and children who had incomplete basic immunization coverage as infants age 9–11 months. In model without LBW, the odds of stunting increased significantly among children who had preterm at birth, short maternal stature and children who had incomplete basic immunization coverage for 9–11 months infants. Conclusions Postnatal factors—preterm birth, low birth weight, diarrhea and complete basic immunization coverage—were associated with infant stunting in Sambas District, Indonesia. The prenatal factors such as short maternal stature were significant in the multivariate model. Policy makers, especially in the government, should recommend measures focused on those prenatal and postnatal factors to prevent stunting in children and to avoid the sequelae of childhood stunting in adult life.

Brain age predicted using graph convolutional neural network explains developmental trajectory in preterm neonates

Dramatic alterations in brain morphology, such as cortical thickness and sulcal folding, occur during the 3rd trimester of gestation which overlaps with the period of premature births. Here, we investigated the ability of the graph convolutional network (GCN) to predict brain age for preterm neonates by accounting for morphometrics measured on the cortical surface and the surface mesh topology as a sparse graph. Our findings demonstrate that GCN-based age prediction of preterm neonates (n=170; mean absolute error [MAE]: 1.06 weeks) outperformed conventional machine learning algorithms and deep learning methods that did not use topological information. We further evaluated how predicted brain age (PBA) emerges as a biologically meaningful index that characterizes the current status of brain development at the time of imaging. We hypothesized that the relative brain age (RBA; PBA minus chronological age) at scan reflects a combination of perinatal clinical factors, including preterm birth, birthweight, perinatal brain injuries, exposure to postnatal steroids, etc. We also hypothesized that RBA of neonatal scans may be associated with brain functional development in the future. To validate these hypotheses, we used general linear models. Furthermore, we established structural equation models (SEM) to determine the structural relationship between preterm birth (as a latent variable of birthweight and birth age), perinatal injuries (as a latent variable of three leading brain injuries), postnatal factors (as a latent variable of six clinical conditions), RBA at scan, and neurodevelopmental scores at 30 months. Our results suggest that low birthweight, chronic lung disease, and exposure to postnatal steroids impair cortical growth, as low RBA was significantly associated with these risks. Furthermore, RBA was associated with cognitive and language scores at 30 months. SEM analysis indicated that RBA mediated the influences of preterm birth and postnatal clinical factors, but not perinatal brain injuries, toward brain functional development at 30 months. The left middle cingulate cortex showed the most accurate prediction of brain age (MAE: 1.19 weeks), followed by left posterior and right middle cingulate cortices (1.21 weeks). These cingulate regions presented faster growth than others. RBAs of several frontal cortices significantly correlated with cognitive abilities at 30 months of age (n=50). Whereas, RBA of left Broca's area, which is important for language production and comprehension, was associated with language functional scores. Overall, our results demonstrate the potential of the GCN in both predicting brain age and localizing regional growth that relates to postnatal factors and future neurodevelopmental outcome.

Does the prenatal factor or the postnatal factor contribute more to changes in the child sex ratio in India? An investigation in the context of fertility and mortality transition

There has been a drastic decline in the child sex ratio (number of females per 1000 males between ages 0 and 4) in India and many of its states. This study aimed to examine if prenatal factors, such as change in sex ratio at birth, or postnatal factors, such as change in relative mortality of females and males, contribute to this more by analysing the dynamics of the child sex ratio. Changes in the child sex ratio during 2001–2011 were decomposed into a ‘fertility’ component attributable to prenatal sex selection and a ‘mortality’ component attributable to sex differentials in postnatal survival at the country as well as the state level. Between the prenatal factor and the postnatal factor, the contribution of the latter to the declining child sex ratio has been greater than the former in India as a whole and in most of the states. By focusing on both prenatal and postnatal factors, the imbalance in the child sex ratio in the country can be reduced to a large extent.

Maternal periconceptual nutrition, early pregnancy, and developmental outcomes in beef cattle

The focus of this review is maternal nutrition during the periconceptual period and offspring developmental outcomes in beef cattle, with an emphasis on the first 50 d of gestation, which represents the embryonic period. Animal agriculture in general, and specifically the beef cattle industry, currently faces immense challenges. The world needs to significantly increase its output of animal food products by 2050 and beyond to meet the food security and agricultural sustainability needs of the rapidly growing human population. Consequently, efficient and sustainable approaches to livestock production are essential. Maternal nutritional status is a major factor that leads to developmental programming of offspring outcomes. Developmental programming refers to the influence of pre-and postnatal factors, such as inappropriate maternal nutrition, that affect growth and development and result in long-term consequences for health and productivity of the offspring. In this review, we discuss recent studies in which we and others have addressed the questions, “Is development programmed periconceptually?” and, if so, “Does it matter practically to the offspring in production settings?” The reviewed studies have demonstrated that the periconceptual period is important not only for pregnancy establishment but also may be a critical period during which fetal, placental, and potentially postnatal development and function are programmed. The evidence for fetal and placental programming during the periconceptual period is strong and implies that research efforts to mitigate the negative and foster the positive benefits of developmental programming need to include robust investigative efforts during the periconceptual period to better understand the implications for life-long health and productivity.