Adverse Outcomes In Preterm Infants Research Articles

Sample entropy correlates with intraventricular hemorrhage and mortality in premature infants early in life.

Mortality and intraventricular hemorrhage (IVH) are common adverse outcomes in preterm infants and are challenging to predict clinically. Sample entropy (SE), a measure of heart rate variability (HRV), has shown predictive power for sepsis and other morbidities in neonates. We evaluated associations between SE and mortality and IVH in the first week of life. Participants were 389 infants born before 32 weeks of gestation for whom bedside monitor data were available. A total of 29 infants had IVH grade 3 or 4 and 31 infants died within 2 weeks of life. SE was calculated with the PhysioNet open-source benchmark. Logistic regressions assessed associations between SE and IVH and/or mortality with and without common clinical covariates over various hour of life (HOL) censor points. Lower SE was associated with mortality by 4 HOL, but higher SE was very strongly associated with IVH and mortality at 24-96 HOL. Bootstrap testing confirmed SE significantly improved prediction using clinical variables at 96 HOL. SE is a significant predictor of IVH and mortality in premature infants. Given IVH typically occurs in the first 24-72 HOL, affected infants may initially have low SE followed by a sustained period of high SE. SE correlates with IVH and mortality in preterm infants early in life. SE combined with clinical factors yielded ROC AUCs well above 0.8 and significantly outperformed the clinical model at 96 h of life. Previous studies had not shown predictive power over clinical models. First study using the PhysioNet Cardiovascular Toolbox benchmark in young infants. Relative to the generally accepted timing of IVH in premature infants, we saw lower SE before or around the time of hemorrhage and a sustained period of higher SE after. Higher SE after acute events has not been reported previously.

Comparing the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia in preterm infants

Objective: To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks. Methods: The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria. Results: The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.02, P=0.984). Conclusion: The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels-a pilot randomized trial.

Deficiencies of citrulline and arginine have been associated with adverse outcomes in preterm-infants and data regarding enteral supplementation in preterm infants is limited. This randomized -trial [NCT03649932] included 42 preterm infants (gestational age ≤33 weeks) randomized to receive enteral L-citrulline in low (100 mg/kg/day), medium (200 mg/kg/day) and high-dose (300 mg/kg/day) groups for 7 days. Plasma citrulline and arginine levels were obtained pre-and-post supplementation and efficacy was determined by a significant increase in levels after supplementation. A p < 0.05 was considered significant. Safety monitoring included blood-pressure-monitoring as well as complications and death during hospitalization. A total of 40/42 (95%) of the recruits completed the 7-day supplementation with no adverse events. Plasma-citrulline levels increased significantly in all three groups while plasma-arginine levels increased significantly in the high-dose group. Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma citrulline and arginine levels. NCT03649932 https://clinicaltrials.gov/ct2/show/NCT03649932 .

Comparison of two novel diagnostic criteria for bronchopulmonary dysplasia in predicting adverse outcomes of preterm infants: a retrospective cohort study

BackgroundThis study aimed to compare the predictive value of two diagnostic criteria for bronchopulmonary dysplasia (BPD) in preterm infants with gestational age (GA) < 32 weeks for death or severe respiratory morbidity at corrected age of 18–24 months.MethodsIn this retrospective cohort study, clinical data from July 2019 to September 2021 were classified by 2018 National Institute of Child Health and Human Development (NICHD) and 2019 Jensen definitions of BPD. Based on the follow-up results, the enrolled population was divided into adverse outcome group and normal outcome group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to explore the risk factors of adverse outcomes and evaluate the predictive value of both diagnostic criteria.ResultsOf 451 infants, 141 (31.3%) had adverse outcomes, which increased with increasing severity of BPD. Logistic regression analysis showed only BPD was an independent risk factor for adverse outcomes in preterm infants. ROC analysis revealed that both diagnostic criteria showed similar predictive values (2018 NICHD definition AUC = 0.771 vs. 2019 Jensen definition AUC = 0.770), with specificities of 93.5% and 96.8%, respectively; however, combining them separately with GA or birth weight did not improve their predictive values.ConclusionsThe two novel definitions of BPD demonstrate similar predictive values in predicting death or severe respiratory morbidity at corrected age of 18–24 months, with higher specificity observed in both.

Establishment of a prediction model for histological chorioamnionitis and its association with outcomes of premature infants.

This study aims to construct a prediction model for histological chorioamnionitis (HCA) and analyze the associations between the predicted risk of HCA and adverse outcomes in preterm infants. In total, 673 subjects were included in this cohort study and divided into HCA group (n = 195) and non-HCA group (n = 478). A stepwise method was used to screen the predictors for HCA, binary logistic regression was used to construct the prediction model, and the associations between the predicted risk of HCA and adverse outcomes were analyzed. HCA occurred in 195 patients, accounting for 29.0%. The sensitivity of the prediction model was 0.821 [95% confidence interval (CI): 0.767-0.874)], the specificity was 0.684 (95% CI: 0.642-0.726), the positive predictive value was 0.514 (0.459-0.570), the negative predictive value was 0.903 (95% CI: 0.873-0.934), the area under the curve was 0.821 (95% CI: 0.786-0.855), and the accuracy was 0.724 (95% CI: 0.690-0.757). The predicted risk of HCA was associated with a higher risk of bronchopulmonary dysplasia (BPD) [odds ratio (OR) = 3.48, 95% CI: 1.10-10.95)], sepsis (OR = 6.66, 95% CI: 2.17-20.43), and neonatal infections (OR = 9.85, 95% CI: 3.59-26.98), but not necrotizing enterocolitis (OR = 0.67, 95% CI: 0.24-1.88), retinopathy of prematurity (OR = 1.59, 95% CI: 0.37-6.85), and brain damage (OR = 1.77, 95% CI: 0.82-3.83). After adjusting for confounders including gestational week at birth and birth weight, the risk of neonatal infections (OR = 5.03, 95% CI: 2.69-9.41) was increased in preterm infants' exposure to HCA. The model showed good predictive performance for identifying pregnant women with a higher risk of HCA. In addition, HCA was associated with the risk of BPD, sepsis, and infections in neonates.

Superior Vena Cava flow in preterm infants and neonatal outcomes: A Systematic review.

Superior vena cava (SVC) flow has been considered a surrogate marker of systemic blood flow in neonates. We conducted a systematic review to evaluate association between low SVC flow recorded during the early neonatal period and neonatal outcomes. We searched the following databases (until Dec 9, 2020; updated October 21, 2022): PROSPERO, OVID Medline, OVID EMBASE, Cochrane Library (CDSR and Central), Proquest Dissertations and Theses Global, and SCOPUS using controlled vocabulary and key words representing the concepts "superior vena cava" and "flow" and "neonate". Results were exported to COVIDENCE review management software. The search retrieved 593 records after removal of duplicates, of which 11 studies (9 cohorts) met the inclusion criteria. The majority of the studies included infants born at <30 weeks of gestation. The included studies were assessed as high risk of bias in terms of incomparability of the study groups, with infants in low SVC flow group noted to be more immature than those in the normal SVC flow group or subjected to different co-interventions. We did not conduct meta-analyses in view of significant clinical heterogeneity noted in the included studies. We found little evidence to suggest that SVC flow in early neonatal period is an independent predictor for adverse clinical outcomes in preterm infants. Included studies were assessed at high risk of bias. SVC flow interpretation for prognostication or for making treatment decisions should be restricted to research setting for now. We highlight the need for strengthened methods in the future research studies.

Respiratory function monitoring during early resuscitation and prediction of outcomes in prematurely born infants.

Over the last decade, there has been increased use of end-tidal carbon dioxide (ETCO2) and oxygen saturation (SpO2) monitoring during resuscitation of prematurely born infants in the delivery suite. Our objectives were to test the hypotheses that low end-tidal carbon dioxide (ETCO2) levels, low oxygen saturations (SpO2) and high expiratory tidal volumes (VTE) during the early stages of resuscitation would be associated with adverse outcomes in preterm infants. Respiratory recordings made in the first 10 min of resuscitation in the delivery suite of 60 infants, median GA 27 (interquartile range 25-29) weeks were analysed. The results were compared of infants who did ordid not die or did or did not develop intracerebral haemorrhage (ICH) or bronchopulmonary dysplasia (BPD). Twenty-five infants (42%) developed an ICH and23 (47%) BPD; 11 (18%) died. ETCO2 at approximately 5min after birth was lower in infants who developed anICH, this remained significant after adjusting for gestational age, coagulopathy and chorioamnionitis (p=0.03). ETCO2 levels were lower in infants who developed ICH or died compared to those that survived without ICH, which remained significant after adjustment for gestational age, Apgar score at 10min, chorioamnionitis and coagulopathy (p=0.004). SpO2 at approximately 5min waslower in the infants who died compared to those who survived which remained significant after adjusting for the5-min Apgar score and chorioamnionitis (p=0.021). ETCO2 and SpO2 levels during early resuscitation in the delivery suite were associated with adverse outcomes.

Essential Fatty Acid Supplementation and Early Inflammation in Preterm Infants: Secondary Analysis of a Randomized Clinical Trial

Introduction: Postnatal inflammation is associated with increased mortality and adverse outcomes in preterm infants. The essential fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) are precursors of lipid mediators with a key role in resolving inflammation. Our aim was to investigate the effect of ARA and DHA supplementation on systemic inflammation in very preterm infants and to identify clinical factors associated with early inflammation. Methods: Secondary analysis of data from a randomized clinical trial (ImNuT study). Infants with gestational age (GA) less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (ARA:DHA group) or MCT oil (control group) from the second day of life to 36 weeks postmenstrual age. ARA, DHA, and four proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were analyzed in repeated dried blood samples from birth to day 28 and the area under the curve (AUC) for each variable was calculated. Results: The intention to treat population included 120 infants with mean (SD) GA 26.4 (1.7). The ARA:DHA group had significantly lower IL-6 levels from day 3 to day 28 compared to the control group, mean difference AUC log₁₀ (95% CI): 0.16 (0.03–0.30) pg/mL, p = 0.018. There was no correlation between ARA or DHA blood concentrations and cytokine levels. Having a low gestational age was independently associated with increased levels of all cytokines during the first 4 weeks of life. Conclusions: Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants.

Antenatal prediction models for outcomes of extremely and very preterm infants based on machine learning.

Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes. A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32weeks of gestation and weighing ≤ 1500g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value. The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes. Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes.

Antibiotic exposure prevents acquisition of beneficial metabolic functions in the preterm infant gut microbiome

BackgroundAberrations in the preterm microbiome following antibiotic therapy have been reported in previous studies. The objective of this study was to probe potential underlying mechanisms between this observation and susceptibility to adverse prematurity-related outcomes.ResultsMetagenomic shotgun sequencing was performed on 133 stool and 253 skin samples collected at 1 and 3 weeks of age from 68 infants born at <36 weeks postmenstrual age and birth weight <2000 g. After accounting for gestational age and maternal antibiotics, the distribution of organisms in all samples and the corresponding metabolic pathway abundance were compared between infants exposed to postnatal antibiotics and antibiotics-naïve infants.In antibiotic-naïve infants, gestational and postnatal age imparted similar trajectories on maturation of the microbial community and associated metabolic functional capacity, with postnatal age exerting greater contribution. Antibiotic exposure was associated with reversal in maturation trajectory from the first week to the third week of age (p< 0.001). Butyrate-producing genera, including Clostridium and Blautia, were significantly more abundant in antibiotic-naïve neonates at 3 weeks postnatal age. Correspondingly, metabolic pathways required for short-chain fatty acid synthesis were significantly increased in antibiotic-naïve infants, but not in antibiotic-exposed neonates, at 3 weeks after birth.ConclusionsEarly brief antibiotic exposure markedly disrupts developmental trajectory of the neonatal microbiome and its corresponding functional capacity. Our findings may provide a mechanistic explanation for the known associations between antibiotic use and adverse outcomes in preterm infants.459naA43GFKEq_9gJQNK48Video

A practical approach toward interpretation of amplitude integrated electroencephalography in preterm infants

This algorithm may be used by clinicians at the bedside for interpretation to integrate it in clinical practice for neurological surveillance of preterm infants. •Studies have reported normative data on aEEG in preterm infants for different gestational ages. • Burst suppression pattern and absent sleep-wake cycling have been described to be associated with brain pathology and adverse outcomes in preterm infants. •We have synthesized aEEG characteristics in preterm infants across the spectrum of prematurity reported in the literature. • We present a stepwise approach for clinically applicable interpretation of aEEG in preterm infants.

Safety and Efficacy of Early High Parenteral Lipid Supplementation in Preterm Infants: A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis was to summarize the effects of early initiation and achievement of a high dose of parenteral lipids (≥1.5 g/kg/day reached within the first 24 h of birth) on growth and adverse outcomes in preterm infants. PubMed, EMBASE, and Cochrane databases were utilized to search for publications for this meta-analysis. Randomized controlled trials were eligible if data on growth or clinical outcome was available. The search returned nine studies. The mean proportion of postnatal weight loss (%) was lower (mean difference [MD]: −2.73; 95% confidence interval [CI]: −3.69, −1.78), and the mean head circumference near the term equivalent age (cm) was higher in the early high lipid treatment group (MD: 0.67; 95% CI: 0.25, 1.09). There was a favorable association of early high lipid administration with the incidence of extrauterine growth restriction (relative risk [RR]: 0.27; 95% CI: 0.15, 0.48). Generally, there were no differences in morbidities or adverse outcomes with early high lipid administration. Early initiation of parenteral lipids and high dose achieved within the first 24 h of life appear to be safe and endurable and offer benefits in terms of growth.

Gastroesophageal Reflux Disease in Neonates: Facts and Figures.

* Abbreviations: AAP: : American Academy of Pediatrics BPD: : bronchopulmonary dysplasia CMPA: : cow milk protein allergy GEJ: : gastroesophageal junction GER: : gastroesophageal reflux GERD: : gastroesophageal reflux disease H2RA: : histamine 2 receptor antagonist LES: : lower esophageal sphincter NASPGHAN: : North American Society of Pediatric Gastroenterology, Hepatology and Nutrition pH-MII: : multichannel intraluminal pH impedance PPI: : proton pump inhibitor SLESR: : swallow-associated lower esophageal sphincter relaxation SSI: : symptom sensitivity index TLESR: : transient lower esophageal sphincter relaxation VLBW: : very low-birthweight Clinicians caring for premature infants need to recognize the natural history and pathophysiology of gastroesophageal reflux (GER) and GER disease. Clinicians also need to make the most out of the diagnostic tools available in their clinical settings and offer the most appropriate therapy for these conditions, which constitute a significant burden to patients and to our health care system. After completing this article, readers should be able to: 1. Explain the terminology, mechanisms, and controversies surrounding gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) in neonates. 2. Describe the epidemiology, pathophysiology, and risk factors of GER and GERD in neonates. 3. Explain the approach to evaluate, diagnose, and manage GERD in neonates. Gastroesophageal reflux (GER) is a normal physiologic process that occurs in all age groups. In healthy preterm infants, an average of 2 to 3 reflux events occur per hour, as has been reported using 24-hour pH impedance monitoring. (1) GER has historically been associated with a wide variety of behaviors commonly attributed to “GERD-like” symptoms in infants. (2) However, the association between a specific symptom and GER needs supporting data. (3) In the NICU infant, many of these symptoms may have multisystemic etiologies related to prematurity, chronic lung disease, and neuropathology, among others, rather than solely GER. Over the years, GER has remained a controversial topic for clinicians because of the challenges that entail its accurate diagnosis, as well as the uncertainty of treatment efficacy in symptomatic neonates. Furthermore, various studies have shown that histamine 2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), and prokinetics therapy may be associated with serious adverse outcomes in preterm infants. (4)(5)(6)(7) In addition, the American Academy of Pediatrics (AAP) through the “Choosing Wisely in Newborn Medicine” initiative highlighted routine use of antireflux medications in symptomatic GER in preterm infants …

Predictors of adverse outcomes in preterm infants in the early neonatal period

Introduction. Extremely and very preterm infants are a special cohort of newborns with inherent functional immaturity and specific pathological conditions which are accompanied by hypoxia, reoxygenation, tissue hypoperfusion, increased risk of oxidative stress. Premature infants are prone to oxidative deterioration which plays a key role in the pathogenesis of severe diseases such as respiratory distress syndrome, necrotizing enterocolitis, periventricular leukomalacia, patent ductus arteriosus, bronchopulmonary dysplasia, and retinopathy of prematurity.Objective. The aim of the research was to estimate the predictors of adverse outcomes in preterm infants with gestational age less than 32 weeks in the early neonatal period by assessment of oxidative stress markers.Material and methods. A total amount of 46 preterm infants with gestational age less than 32 weeks in the early neonatal period were included in the research. According to the results of early outcomes newborns were divided into two groups: I group – 12 infants with adverse outcomes and II group - 34 preterm infants with favorable outcomes. Twenty healthy newborns were included in the control group (III group). Clinical examination of infants and laboratory determination of oxidative stress markers were done for all participants.Results. Asphyxia, early onset sepsis, intraventricular hemorrhage in preterm infants less than 32 weeks of gestation had increased the risk of mortality in the early neonatal period. The level of 8-isoprostane, ROS, TBP, LHP was significantly higher in neonates with adverse outcomes (group I). It was found that the level of 8-isoprostane more than 595.4 mg/ml, ROS level above 0.483 IU, TBP higher than 5.14 μmol/l and LHP levels above 5.91 U/m were associated with unfavorable outcomes in the early neonatal period. Decreased activity of the antioxidant system (catalase, SOD) increases the risk of early neonatal mortality.Conclusions. The activation of oxidative stress in preterm infants may be a predictor of adverse outcomes in the early neonatal period.

Low cardiac output measured by bioreactance and adverse outcome in preterm infants with birth weight less than 1250 g

BackgroundRecently a new continuous non-invasive cardiac output measurement, bioreactance, has become available. Bioreactance measurement of cardiac output has been shown to correlate with left ventricular output detected by echocardiography in healthy term and preterm neonates. AimsOur aim was to correlate cardiac output measurements by bioreactance in the first 48 h of life with adverse outcomes attributable to hypoperfusion (peri/intraventricular haemorrhage (PIVH) and/or necrotising enterocolitis (NEC)) in the cohort of extremely preterm infants. Study designA prospective observational cohort study. SubjectsPreterm infants with birth weight less than 1250 g. Outcome measuresCardiac output was measured between six and 48 h of age by bioreactance. Our primary outcome was a difference in cardiac output between infants with an adverse outcome attributable to hypoperfusion (Group 1), and infants without the predefined adverse outcome (Group 2). ResultsThere were 39 infants enrolled in the study. There were six infants in Group 1. These infants had a significantly lower minimal cardiac output measurement compared to Group 2 (mean 36.7 ml/kg/min vs 64.5 ml/kg/min, p = .0006). The mean cardiac output in Group 1 was significantly lower on day one of life, followed by a significant increase in cardiac output on day two of life compared to Group 2. ConclusionsInfants with birth weight less than 1250 g and PIVH and/or NEC had significantly lower cardiac output compared to infants without these complications on day one of life. This low cardiac output was then followed by a significant increase on day two of life.

Placental finding among extremely preterm infants with moderate to severe bronchopulmonary dysplasia

Background: Fetal exposure to maternal inflammation has been reported with various adverse outcomes in preterm infants. Histological chorioamnionitis has been variably reported to be associated with the development of lung disease including bronchopulmonary Dysplasia (BPD). Most investigators have reported the association of acute inflammatory lesions and maternal vascular under perfusion on placental histopathology with BPD in preterm neonates. Objective: To determine if pre-specified placental abnormalities among preterm infants with moderate to severe BPD differ compared to infants with No/Mild BPD. Methods: Preterm infants, …

Predicting motor outcome in preterm infants from very early brain diffusion MRI using a deep learning convolutional neural network (CNN) model

Background and aimsPreterm birth imposes a high risk for developing neuromotor delay. Earlier prediction of adverse outcome in preterm infants is crucial for referral to earlier intervention. This study aimed to predict abnormal motor outcome at 2 years from early brain diffusion magnetic resonance imaging (MRI) acquired between 29 and 35 weeks postmenstrual age (PMA) using a deep learning convolutional neural network (CNN) model. MethodsSeventy-seven very preterm infants (born <31 weeks gestational age (GA)) in a prospective longitudinal cohort underwent diffusion MR imaging (3T Siemens Trio; 64 directions, b ​= ​2000 ​s/mm2). Motor outcome at 2 years corrected age (CA) was measured by Neuro-Sensory Motor Developmental Assessment (NSMDA). Scores were dichotomised into normal (functional score: 0, normal; n ​= ​48) and abnormal scores (functional score: 1–5, mild-profound; n ​= ​29). MRIs were pre-processed to reduce artefacts, upsampled to 1.25 ​mm isotropic resolution and maps of fractional anisotropy (FA) were estimated. Patches extracted from each image were used as inputs to train a CNN, wherein each image patch predicted either normal or abnormal outcome. In a postprocessing step, an image was classified as predicting abnormal outcome if at least 27% (determined by a grid search to maximise the model performance) of its patches predicted abnormal outcome. Otherwise, it was considered as normal. Ten-fold cross-validation was used to estimate performance. Finally, heatmaps of model predictions for patches in abnormal scans were generated to explore the locations associated with abnormal outcome. ResultsFor the identification of infants with abnormal motor outcome based on the FA data from early MRI, we achieved mean sensitivity 70% (standard deviation SD 19%), mean specificity 74% (SD 39%), mean AUC (area under the receiver operating characteristic curve) 72% (SD 14%), mean F1 score of 68% (SD 13%) and mean accuracy 73% (SD 19%) on an unseen test data set. Patch-based prediction heatmaps showed that the patches around the motor cortex and somatosensory regions were most frequently identified by the model with high precision (74%) as a location associated with abnormal outcome. Part of the cerebellum, and occipital and frontal lobes were also highly associated with abnormal NSMDA/motor outcome. Discussion/conclusionThis study established the potential of an early brain MRI-based deep learning CNN model to identify preterm infants at risk of a later motor impairment and to identify brain regions predictive of adverse outcome. Results suggest that predictions can be made from FA maps of diffusion MRIs well before term equivalent age (TEA) without any prior knowledge of which MRI features to extract and associated feature extraction steps. This method, therefore, is suitable for any case of brain condition/abnormality. Future studies should be conducted on a larger cohort to re-validate the robustness and effectiveness of these models.

Genetic predisposition for vitamin D deficiency is not associated with adverse outcome of very low birth weight infants: A cohort study from the German Neonatal Network.

ObjectivePostnatal vitamin D supplementation is standard of care in neonates and preterm infants. Despite routine supplementation of vitamin D, a wide range of complications related to vitamin D deficiency has been described in the literature. Since standard vitamin D supplementation might be not sufficient in preterm infants with a genetic predisposition for vitamin D deficiency, we investigated the outcome of preterm infants with regard to their genetic estimated vitamin D levels.MethodsPreterm infants with a birth weight below 1500 grams were included in the German Neonatal Network at the time of their birth and tested at the age of five. The vitamin D level was genetically calculated based on three single nucleotide polymorphisms (SNPs: rs12794714, rs7944926 and rs2282679) which alter vitamin D synthesis pathways. Specific alleles of these polymorphisms are validated markers for low plasma vitamin D levels. Outcome data were based on baseline data at the time of birth, typical complications of prematurity, body measurements at the age of five and occurrence of bone fractures. T-test and Fisher’s exact test were used for statistical comparison.ResultsAccording to their genetic predisposition, 1,924 preterm infants were divided into groups of low (gsVitD < 20. Percentile), intermediate and high vitamin D level estimates. Low genetic vitamin D level estimates could not be shown to be associated with any adverse outcome measures examined. The analyses covered data on aforementioned determinants.ConclusionLow genetic vitamin D level estimates could not be shown to be associated with previously described adverse outcome in preterm infants.

Risk factors for prognosis of premature infants with septic shock: analysis of 114 cases

Objective To investigate the risk factors affecting the prognosis of preterm infants with septic shock. Methods A retrospective study was conducted to analyze the clinical data of 114 preterm children with septic shock admitted to the Neonatal Intensive Care Unit (NICU) of the PLA Army General Hospital from February 2014 to January 2017. According to the outcomes, these cases were divided into two groups, the cured group and the death group (including those died after ineffective treatment and withdrawal of treatment). Clinical data including the general clinical data, perinatal risk factors, clinical features and prognosis of the two groups of children, as well as the occurrence of related complications were statistically analyzed by t-test, Wilcoxon nonparametric test, Chi-square test or Fisher's exact probability method. Logistic regression was used to analyze the factors influencing the prognosis. Predictive values of the indicators were evaluated using receiver operating characteristic (ROC) curve. Results (1) Among the 114 patients, 87(76.3%) were cured and 27(23.7%) were dead. (2) In the death group, there were more infants complicated with amniotic fluid pollution, anemia and thrombocytopenia (platelet count <100×109/L) and the C-reactive protein (CRP) levels were higher than those in the cured group [29.6% (8/27) vs 8.1% (7/87), χ2=6.618; 22.2% (6/27) vs 5.9% (5/87), χ2=4.665; 59.3% (16/27) vs 23.3% (20/87), χ2=12.546; 36.0 (1.0-80.0) mg/L vs 7.5 (1.0-25.0) mg/L, Z=2.400], while the hemoglobin level was lower [(122.2±43.3) g/L vs (140.5±34.4) g/L, t=2.260] (all P<0.05). (3) The percentages of infants with patent ductus arteriosus, pulmonary hemorrhage and coagulopathy in the death group were higher than those in the cured group [81.5% (22/27) vs 60.9% (53/87), χ2=3.871; 37.0% (10/27) vs 12.6% (11/87), χ2=6.616; 48.2% (13/27) vs 20.7% (18/87), χ2=7.847; all P<0.05]. (4) Multivariate logistic regression analysis showed that amniotic fluid contamination, coagulopathy, patent ductus arteriosus and CRP level were risk factors for poor prognosis in neonates (all P<0.05). (5) A total of 77 pathogens were isolated from the 114 infants with 66 in the cured group and 11 in the death group. Pathogens of Gram-positive and Gram-negative bacteria and fungi in the cured and death groups accounted for 37.9% (25/66) vs 3/11, 37.9% (25/66) vs 6/11, and 24.2% (16/66) vs 2/11, respectively. No significant difference in pathogen distribution was observed between the two groups. (6) The area under the ROC curve of CRP was 0.649 (P=0.024). When the cut-off value of CRP was set at 31 mg/L, the sensitivity and specificity for predicting adverse outcomes in preterm infants with septic shock were 0.802 and 0.556, respectively, and the Yoden index was 0.358. The area under the ROC curve of thrombocytopenia was 0.708 (P<0.001). When the platelet level was set at 94×109/L, its sensitivity and specificity were 0.767 and 0.593, respectively, and the Yoden index was 0.360. Conclusions Amniotic fluid contamination, patent ductus arteriosus, coagulopathy and elevated CRP are important risk factors for death in preterm infants with septic shock. Thrombocytopenia and persistently elevated CRP has predictive values for the prognosis of preterm infants with sepsis shock. Key words: Shock, septic; Infant, premature; C-reactive protein; Infant death; Risk factors

Effect of probiotics on C-reactive protein levels in preterm infants: Secondary analysis of a randomized controlled trial.

Excessive inflammation is associated with adverse outcomes in preterm infants. C- reactive protein (CRP) is a marker of inflammation/infection. Probiotics have anti-inflammatory properties. Randomized controlled trials (RCTs) in preterm infants have not reported effect of probiotics on CRP. To evaluate effect of probiotics on CRP in preterm infants who had participated in a RCT of Bifidobacterium breve (B. breve) m-16v. Data on all infants (GA <33 weeks, n = 159) enrolled in the RCT was analyzed. For study purpose, CRP <15 mg/L and ≤10 mg/L was considered normal for the first week, and thereafter respectively. Mixed logistic regression modelling was used to assess probiotic effect on CRP levels. There were 1579 CRP measurements (Probiotic: 851 vs. Placebo: 728). Baseline characteristics and number [Median (IQR)] of CRP estimations per infant [l0 (5, 20) vs. 10 (6, 17), p = 0.861] were comparable between probiotic vs. placebo group. There was no significant difference in the proportion of infants with high CRP over time (treatment by weekly time points interaction, p = 0.187), and across all time points between probiotic and placebo group (adjusted OR: 1.62, 95% CI: 0.91-2.88, p = 0.102)CONCLUSION:B. breve m-16v did not decrease CRP levels in preterm infants born <33 weeks.