Association between the development of bronchopulmonary dysplasia and platelet transfusion: a protocol for a systematic review and meta-analysis.

Background: There is a lack of consensus on the management of thrombocytopenia in preterm infants, and the threshold for prophylactic platelet transfusion varies widely among clinicians and institutions. Reports in animal models suggested that platelets may play a relevant role in lung alveolarization and regeneration. Bronchopulmonary dysplasia (BPD) is a severe respiratory condition with a multifactorial origin that affects infants born at the early stages of lung development. Recent randomized controlled trials on the platelets count threshold for prophylactic transfusions in preterm infants with thrombocytopenia suggest that a higher exposition to platelet transfusion may increase the risk of BPD. Here, we report a protocol for a systematic review, which aims to assist evidence-based clinical practice and clarify if the administration of platelet products may be associated with the incidence of BPD and/or death in preterm infants. Methods: MEDLINE, Embase, Cochrane databases, and sources of gray literature for conference abstracts and trial registrations will be searched with no time or language restrictions. Case-control studies, cohort studies, and nonrandomized or randomized trials that evaluated the risk for BPD and/or death in preterm infants exposed to platelet transfusion will be included. Data from studies that are sufficiently similar will be pooled as appropriate. Data extraction forms will be developed a priori. Observational studies and nonrandomized and randomized clinical trials will be analyzed separately. Odds ratio with 95% confidence interval (CI) for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes will be combined. The expected heterogeneity will be accounted for using a random-effects model. Subgroup analysis will be performed based on a priori-determined covariate of interest. In case of sufficient homogeneity of interventions and outcomes evaluated, results from subgroups of studies will be pooled together in a meta-analysis. Discussion: This systematic review will investigate the association of BPD/death with platelet components administration in preterm infants, and, consequently, it will provide reliable indications for the evidence-based management of premature patients with thrombocytopenia.

Less is more: Antibiotics at the beginning of life.

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

Effect of Targeted vs. Standard Fortification of Breast Milk on Growth and Development of Preterm Infants (≤32 Weeks): Results from an Interrupted Randomized Controlled Trial.

Human milk is recommended for very low birth weight infants. Their nutritional needs are high, and the fortification of human milk is a standard procedure to optimize growth. Targeted fortification accounts for the variability in human milk composition. It has been a promising alternative to standard fixed-dose fortification, potentially improving short-term growth. In this trial, preterm infants (≤32 weeks of gestation) were randomized to receive human milk after standard fortification (HMF, Nutricia) or tailored fortification with modular components of proteins (Bebilon Bialko, Nutricia), carbohydrates (Polycal, Nutricia), and lipids (Calogen, Nutricia). The intervention started when preterms reached 80 mL/kg/day enteral feeds. Of the target number of 220 newborns, 39 were randomized. The trial was interrupted due to serious intolerance in five cases. There was no significant difference in velocity of weight gain during the supplementation period (primary outcome) in the tailored vs. standard fortification group: 27.01 ± 10.19 g/d vs. 25.84 ± 13.45 g/d, p = 0.0776. Length and head circumference were not significantly different between the groups. We found the feasibility of targeted fortification to be limited in neonatal intensive care unit practice. The trial was registered at clinicaltrials.gov NCT:03775785.

Artificial intelligence in the diagnosis of necrotising enterocolitis in newborns.

Necrotising enterocolitis (NEC) is one of the most common diseases in neonates and predominantly affects premature or very-low-birth-weight infants. Diagnosis is difficult and needed in hours since the first symptom onset for the best therapeutic effects. Artificial intelligence (AI) may play a significant role in NEC diagnosis. A literature search on the use of AI in the diagnosis of NEC was performed. Four databases (PubMed, Embase, arXiv, and IEEE Xplore) were searched with the appropriate MeSH terms. The search yielded 118 publications that were reduced to 8 after screening and checking for eligibility. Of the eight, five used classic machine learning (ML), and three were on the topic of deep ML. Most publications showed promising results. However, no publications with evident clinical benefits were found. Datasets used for training and testing AI systems were small and typically came from a single institution. The potential of AI to improve the diagnosis of NEC is evident. The body of literature on this topic is scarce, and more research in this area is needed, especially with a focus on clinical utility. Cross-institutional data for the training and testing of AI algorithms are required to make progress in this area. IMPACT: Only a few publications on the use of AI in NEC diagnosis are available although they offer some evidence that AI may be helpful in NEC diagnosis. AI requires large, multicentre, and multimodal datasets of high quality for model training and testing. Published results in the literature are based on data from single institutions and, as such, have limited generalisability. Large multicentre studies evaluating broad datasets are needed to evaluate the true potential of AI in diagnosing NEC in a clinical setting.

Effects of Early versus Standard Central Line Removal on the Growth of Preterm Infants with Very Low Birth Weight: A Non-Inferiority, Randomized Clinical Trial.

Very preterm infants are usually supported by parenteral nutrition delivered through central lines (CLs) while progressing with enteral intake, although the optimal time point for their removal is unclear. This study evaluated the impact of the CL discontinuation time on the short-term growth outcomes of preterm infants. A non-inferiority, parallel-group, randomized controlled trial was conducted in four neonatal intensive care units in Poland. Preterm infants with very low birth weight (VLBW) without congenital abnormalities were eligible. Patients were allocated to discontinue central access at an enteral feeding volume of 100 mL/kg/day (intervention group) or 140 mL/kg/day (control group). The study's primary outcome was weight at 36 weeks' postmenstrual age, with a non-inferiority margin of -210 g. Overall, 211 patients were allocated to the intervention or control groups between January 2019 and February 2021, of which 101 and 100 were eligible for intention-to-treat analysis, respectively. The mean weight was 2232 g and 2200 g at 36 weeks' postmenstrual age in the intervention and control groups, respectively. The mean between-group difference was 32 g (95% confidence interval, -68 to 132; p = 0.531), which did not cross the specified margin of non-inferiority. No intervention-related adverse events were observed. Early CL removal was non-inferior to the standard type for short-term growth outcomes in VLBW infants.

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. Design, Setting, and Participants: This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. Exposures: Exposure to antibiotics started in the first postnatal week. Main Outcomes and Measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. Conclusions and Relevance: The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.

Effect of standardized vs. local preoperative enteral feeding practice on the incidence of NEC in infants with duct dependent lesions: Protocol for a randomized control trial.

Background: Infants with duct dependent heart lesions often require invasive procedures during the neonatal or early infancy period. These patients remain a challenge for pediatric cardiologists, neonatologists, and intensive care unit personnel. A relevant portion of these infant suffer from respiratory, cardiac failure and may develop NEC, which leads to inadequate growth and nutrition, causing delayed or complicated cardiac surgery. Methods: This randomized control trial will recruit term infants diagnosed with a duct dependant lesion within the first 72 h of life. After obtaining written parental consent patients will be randomized to either the physician led enteral feeding or protocol-based feeding group. The intervention will continue up to 28 days of life or day of cardiosurgical treatment, whichever comes first. The primary outcomes include NEC and death related to NEC. Secondary outcomes include among others, number of interrupted feedings, growth velocity, daily protein and caloric intake, days to reach full enteral feeding and on mechanical ventilation. Discussion: Our study will be the first randomized control trial to evaluate if standard (as in healthy newborns) initiation and advancement of enteral feeding is safe, improves short term outcomes and does not increase the risk of NEC. If the studied feeding regime proves to be intact, swift implementation and advancement of enteral nutrition may become a recommendation. Trial registration: The study protocol has been approved by the local ethical board. It is registered at ClinicalTrials.gov NCT05117164.

Steroid use for established bronchopulmonary dysplasia: study protocol for a systematic review and meta-analysis.

INTRODUCTION: Postnatal steroids during the first few weeks of life have been demonstrated to be effective in decreasing the incidence of bronchopulmonary dysplasia (BPD), a serious chronic respiratory condition affecting preterm infants. However, this preventive option is limited by the concern of neurological side effects. Steroids are used to treat established BPD in an attempt to reduce mortality, and length of stay and home oxygen therapy, both of which associated with high levels of parental stress and healthcare costs. Moreover, a late timing for steroid treatment may show a more favourable safety profile in terms of neurodevelopment outcomes, considering the added postnatal brain maturation of these infants. Here, we report a protocol for a systematic review, which aims to determine the efficacy and long-term safety of postnatal steroids for the treatment of established BPD in preterm infants. METHODS AND ANALYSIS: MEDLINE, Embase, Cochrane databases and sources of grey literature for conference abstracts and trial registrations will be searched with no time or language restriction. We will include case-control studies, cohort studies and non-randomised or randomised trials that evaluate postnatal steroids for infants diagnosed with moderate or severe established BPD at 36 weeks' postmenstrual age. We will pool data from studies that are sufficiently similar to make this appropriate. Data extraction forms will be developed a priori. Observational studies and non-randomised and randomised clinical trials will be analysed separately. We will combine OR with 95% CI for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes. We will account for the expected heterogeneity by using a random-effects model. We will perform subgroup analysis based on the a priori determined covariate of interest. ETHICS AND DISSEMINATION: Systematic reviews are exempted from approval by an ethics committee. Attempts will be sought to publish all results. PROSPERO REGISTRATION NUMBER: CRD42021218881.

Deep learning fetal ultrasound video model match human observers in biometric measurements.

Objective.This work investigates the use of deep convolutional neural networks (CNN) to automatically perform measurements of fetal body parts, including head circumference, biparietal diameter, abdominal circumference and femur length, and to estimate gestational age and fetal weight using fetal ultrasound videos.Approach.We developed a novel multi-task CNN-based spatio-temporal fetal US feature extraction and standard plane detection algorithm (called FUVAI) and evaluated the method on 50 freehand fetal US video scans. We compared FUVAI fetal biometric measurements with measurements made by five experienced sonographers at two time points separated by at least two weeks. Intra- and inter-observer variabilities were estimated.Main results.We found that automated fetal biometric measurements obtained by FUVAI were comparable to the measurements performed by experienced sonographers The observed differences in measurement values were within the range of inter- and intra-observer variability. Moreover, analysis has shown that these differences were not statistically significant when comparing any individual medical expert to our model.Significance.We argue that FUVAI has the potential to assist sonographers who perform fetal biometric measurements in clinical settings by providing them with suggestions regarding the best measuring frames, along with automated measurements. Moreover, FUVAI is able perform these tasks in just a few seconds, which is a huge difference compared to the average of six minutes taken by sonographers. This is significant, given the shortage of medical experts capable of interpreting fetal ultrasound images in numerous countries.

Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7-32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n = 55; approximately 800-1000 IU from combined sources) or monitored therapy (n = 54; with an option of dose modification). 25-hydroxyvitamin D [25(OH)D] concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52 ± 2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (>90 ng/mL) at 40 weeks of PCA. A significantly higher infants' percentage in the monitored group had safe vitamin D levels (20-80 ng/mL) at 52 weeks of PCA (p = 0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800-1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

The risk of hyperbilirubinemia in term neonates after placental transfusion - a randomized-blinded controlled trial.

OBJECTIVE: We aimed to demonstrate non-inferiority of delayed cord clamping (DCC) and cord milking (CM) in comparison to early cord clamping (ECC) in the incidence of hyperbilirubinemia requiring phototherapy. MATERIAL AND METHODS: 467 of maternal-foetal dyads were screened for eligibility. 389 term infants, of breastfeeding, non-smoking mothers were randomized to receive ECC ( < 40 s), DCC (1-2 min) or CM (4 times towards the neonate). The primary outcome was defined as hyperbilirubinemia requiring phototherapy. RESULTS: 307 patients were included in the analysis. CM did not increase the risk of phototherapy RR 11.27 95% CI (0.80; 2.04). Similar results were achieved when comparing DCC and ECC, RR 1.29 95% CI (0.82; 2.05). This was also true for CM vs DCC, RR 0.99 95% CI (0.64; 1.52). The prevalence of total serum bilirubin (TSB) at 24-48 hours was 10.8 mg/dL; 10.33 mg/dL and 11.39 in ECC, CM and DCC group respectively. Transcutaneous bilirubin (TcB) levels at 24-48 h were 7.58 mg/dL, 7.89 mg/dL and 7.60 mg/dL in the ECC, CM and DCC respectively. None of the neonates met exchange transfusion criteria or symptomatic polycythaemia. CONCLUSIONS: Our study suggests that placental transfusion is not associated with hyperbilirubinemia requiring phototherapy or exchange transfusion.

Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (≤ 32 weeks): study protocol for a randomized controlled trial.

BACKGROUND: Human milk is recommended for all very low birth weight infants. Breastmilk is highly variable in nutrient content, failing to meet the nutritional demands of this group. Fortification of human milk is recommended to prevent extrauterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation. METHODS: This randomized controlled trial will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomized to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialka, Nutricia-protein; Polycal, Nutricia-carbohydrates; Calogen, Nutricia-lipids). The intervention will continue until 37 weeks of post-conception age or hospital discharge. Parents and outcome assessors will be blinded to the intervention. The primary outcome measure is velocity of weight, length, and head growth until 36 weeks post-conceptional age or discharge. Secondary outcomes include neurodevelopment at 12 months assessed with Bayley Scale of Development III, repeated at 36 months; body composition at discharge and at 4 months; and incidence of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia. DISCUSSION: Targeted fortification has previously been shown as doable in the neonatal intensive care unit context. If it shows to improve growth and neonatal outcome, choosing the targeted fortification as a first line nutritional approach in very low birth weight infants may become a recommendation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03775785 , Registered on July 2019.

Sensitivity and specificity of different imaging modalities in diagnosing necrotising enterocolitis in a Polish population of preterm infants: a diagnostic test accuracy study protocol.

INTRODUCTION: Necrotising enterocolitis (NEC) is one of the most serious conditions in newborn infants, affecting up to 10% of very low birth weight (VLBW) infants. Mortality rates can rise as high as 60%.The suspected diagnosis is confirmed with typical findings on abdominal radiography (AR) such as pneumatosis intestinalis (PI), portal vein gas (PVG) and in extreme cases pneumoperitoneum. Abdominal ultrasound (AUS) can depict PI, PVG and pnuemoperitoneum (in some cases ahead of AR), but it also provides other crucial information such as bowel wall viability (thickness or thinning) and free abdominal fluid. These additional findings are helpful in diagnosing and managing NEC. METHODS AND ANALYSIS: The hypothesis being tested is that preforming an AR in patients with clinical symptoms of NEC, but inconclusive/normal AR will enhance detection rates, and expedite treatment in infants born at <32 weeks. Additionally, the time needed to initiate treatment, according to decision made based on AR or AR and AUS will also be compared. The use of AUS together with AR as an add-on test may increase the accuracy of diagnosing NEC and expedite life-saving treatment. We plan to recruit 200 VLBW infants, who are most prone to NEC. It will also be the first multicentre study evaluating the use of AUS as an add-on test, enabling us to recruit a significantly higher number of patients compared with published studies. ETHICS AND DISSEMINATION: The Bioethical Committee of the Medical University of Warsaw has approved the study (KB 130/2017). We plan to submit our findings to international peer-reviewed journals. Abstract will be submitted to local and international conferences. TRIAL REGISTRATION NUMBER: NCT03188380; Protocol version: V.2.08.2019; Pre-results.

International consensus is needed on premedication for non-emergency neonatal intubation after survey found wide-ranging policies and practices in 70 countries.

AIM: This study evaluated whether practitioners from 70 countries used premedication for non-emergency neonatal intubation and identified attitudes and experience regarding the safety, side effects and efficiency of neonatal intubation. METHODS: Invitations to take part in the survey were issued between December 18, 2018 and February 4, 2019 to the users of neonatal-based websites and Facebook groups, members of professional societies and the authors of relevant publications in the last five years. RESULTS: We analysed 718 completed questionnaires from 40 European and 30 non-European countries. Most of the responses were from neonatologists (69.6%) and paediatric or neonatal trainees (10.3%). In units without a protocol (31.6%), more than half of the practitioners (60.4%) chose premedication according to personal preference and 37.0%-11.9% of the overall respondents did not use any drugs for non-emergency intubation. The most frequently reported drug combination was fentanyl, atropine and succinylcholine (6.8%). Most of the practitioners (78.5%) use the same drugs for term and preterm infants. Only 24.8% of the physicians were fully satisfied with their premedication practices. CONCLUSION: Nearly 12% of the respondents did not use premedication for non-emergency neonatal intubation. The wide-ranging policies and practices found among the respondents highlight the need for international consensus guidelines.

Effect of early versus standard central line removal on growth of very low birthweight premature infants: a protocol for a non-inferiority randomised controlled trial.

INTRODUCTION: Uncertainty exists regarding the optimal time for removal of central lines used to provide parenteral nutrition in preterm infants. The aim of this study is to determine whether earlier central line removal is non-inferior to its removal after reaching full enteral intake, in respect to growth outcome of preterm infants. METHODS AND ANALYSIS: Very low birthweight premature infants will be recruited. Eligible infants will be randomised in equal proportions between two groups. In the intervention group central lines will be removed when infants reach 100 mL/kg/day of enteral intake. In the control group central lines will be removed when infants reach 140 mL/kg/day of enteral intake (full enteral intake). The primary outcome measure will be the difference between the two groups in weight at 36 weeks' postmenstrual age. Non-inferiority will be declared if the mean weight of children in the intervention group will be no worse than the mean weight of children from the control group, by a margin of -210 g. ETHICS AND DISSEMINATION: The Bioethics Committee of the Medical University of Warsaw approved the study protocol prior to recruitment. The findings of this trial will be submitted to a peer-reviewed journal (neonatology, paediatrics or nutrition). Abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: NCT03730883. PROTOCOL VERSION: Version 3. 14.08.2019.

Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

INTRODUCTION: Preterm birth (PTB) at <37 weeks of gestation is the leading cause of perinatal morbidity and mortality in developed countries. The traditional approach has been based on the assumption that PTB is primarily a result of intrauterine infection, which triggers preterm labour and puts the newborn at risk of early onset sepsis (EOS). We are currently experiencing a rise in prematurity that results from maternal and fetal diseases unrelated to infection. We have designed a systematic review to assess whether chemoprophylaxis should be withheld when the aetiology of preterm birth is non-infectious. METHODS AND ANALYSIS: Our study will focus on studies evaluating EOS in preterm infants. We will conduct a comprehensive search of literature available up to 28 February 2018. An information specialist will search for eligible studies in Medline (Ovid interface, 1948 and onwards), Embase (Ovid interface, 1980 onwards) and the Cochrane Central Register of Controlled Trials (Wiley interface, current issue). We will search databases and registries including records of ongoing research, conference proceedings and thesis (clinical trials, WHO International Clinical Trials Registry Platform). Two authors will independently extract data from eligible studies and assess risk of bias. For continuous outcomes, which follow discrete distribution, mean difference will be calculated. Dichotomous data will be presented using risk ratios, while count data will be expressed using rate ratios. Time-to-event outcomes will be reported as HRs. All estimates will be presented together with 95% CI. Studies comparable with respect to methodology and reporting the same outcomes will be combined in a meta-analysis. ETHICS AND DISSEMINATION: Our systematic review does not require approval from the research and ethics board. We will use the findings to prepare a future multicentre randomised control trial in order to establish safe and adequate antibiotics policies for preterm infants, based on the aetiology of PTB. PROSPERO REGISTRATION NUMBER: CRD42016029707.

MOnitored supplementation of VItamin D in preterm infants (MOSVID trial): study protocol for a randomised controlled trial.

BACKGROUND: The pivotal role of vitamin D (vit D) in skeletal health is well known. Neonatal vit D storage at birth is dependent on maternal levels, and newborns receive 50-70% of their mother's 25-hydroxyvitamin D [25(OH)D]. Deficiency of vit D can lead to prematurity bone disease, with an incidence of up to 55% in infants weighing < 1000 g. The aim of this study is to assess the effectiveness of monitored supplementation of vit D in a population of preterm infants. METHODS/DESIGN: Preterm infants born at 24-32 weeks of gestation will be recruited within the first 7 days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7 days of life, vit D supplementation will consist of 500 IU and an additional 150-300 IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190 IU/kg in milk formulas. Subjects will be randomised to either monitored (with an option of dose modification based on 25(OH)D levels as per protocol) or standard therapy up to 52 weeks of post-conceptional age (PCA). The primary outcome measure will be the number of neonates with deficiency or excess levels of 25(OH)D at 40 ±2 weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8 weeks of age, and/or at 35 and 52 ±2 weeks of PCA. Secondary objectives will include the incidence of osteopenia, nephrocalcinosis and nephrolithiasis. Serum parameters of calcium phosphorus metabolism will also be measured. DISCUSSION: Despite multiple years of research and numerous publications, there is still a lack of consensus in regard to how much vit D infants should receive and how long they should receive it. Because 80% of calcium and phosphorus placental transfer occurs between 24 and 40 weeks of gestation, preterm infants are especially prone to adverse effects of vit D insufficiency. However, both inadequate and excessive amounts of vit D may be unsafe and lead to serious health issues. The results of our study may shed new light on these concerns and contribute to optimising vit D supplementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03087149 . Registered on 15 March 2017.

Neonatal outcome of preterm infants born to mothers with abnormal genital tract colonisation and chorioamnionitis: a cohort study.

PURPOSE: We hypothesised that abnormal genital tract colonisation leading to an in utero inflammation/infection process, contributes to the risk of respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), intra ventricular haemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC) in preterm infants. METHODS: 396 placentas and umbilical cords of neonates born at 22-32weeks of gestation were evaluated. Genital tract and amniotic fluid swabs were cultured for aerobic and anaerobic bacteria. RESULTS: Chorioamnionitis significantly increases the risk for RDS (OR 1.74, 95% CI 1.14-2.65), NEC (OR 3.22, 95% CI 1.36-3.28) and ROP>2 (OR 2.12, 95% CI 1.33-3.36). But the risk for IVH, PDA and BPD did not differ between the groups. Klebsiella pneumoniae (OR 5.33, 95% CI 1.06-26.79), Staphylococcus sp. (OR 18.39, 95% CI 2.32-145.2) and Enterococcus faecalis (OR 10.7, 95% CI 1.27-89.9) showed a significant relationship with intrauterine inflammation processes. E. faecalis increased the risk for NEC (OR 6.13, 95% CI 1.059-37.6). We did not note a link between ROP and genital tract colonisation. Interestingly PDA seems to be triggered by the presence of Pseudomonas aeruginosa (OR 2.38 95% CI 1.83-3.82). CONCLUSION: Our results show a link between K. pneumoniae, Staphylococcus sp., E. faecalis and intrauterine infection. E. faecalis increases the risk for NEC, and suggests a direct link between gram + bacteria, chorioamnionitis and NEC.

The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial.

BACKGROUND AND AIM: Intestinal flora of preterms, dominantly presents with decreased amounts of physiological microbiota. This double blinded randomized control trial compared the stool of bottle fed preterms, randomized to receive lactobacillus rhamnosus GG (LGG) 6x109or placebo with formula feeding. STUDY DESIGN: 46 enterally fed preterms were randomized to receive probiotics or placebo within 0-3days after birth. All personnel were blinded to treatment assignment. Faecal sampling was preformed at day 7, 21, 42. Presence of LGG colonization, somatic growth and length of hospital stay were recorded. RESULTS: 60 patients were initially identified and enrolled but after exclusion criteria were applied, 21 babies were analyzed in the probiotic group and 26 in the placebo group. The number of lactobacillus were significantly higher (p=0.014) on day 7, and 21 (p=0.024) in the study group, and so was the number of enterobacteriaceae on all study days (p=0.004, p=0.000, p=0.000), and Enterococcus sp on day 21 (p=0.000). The amount of samples positive for staphylococci was significantly higher in the study group, on days 7 and 42 (p=0.001 and 0.011). We did not show a significant difference in weight gain upon discharge between the groups p=0.567, 95% CI (-168; 305) or mean of hospital stay p=0.421 95% CI (-13.43;5.71). CONCLUSIONS: A preterm infant formula with an addition of probiotics leads to a rapid growth of LGG in the gut of bottle fed infants, but does not decrease the amount of pathogenic organisms, nor increase weight gain during enteral feeding, or decrease length of hospital stay.