Normal range and risk factors for deviating body temperatures during the first 24 hours in term-born infants under standardised care: an observational study.

OBJECTIVE: Body temperature for a known ambient temperature is not known for infants born at term. We aimed to determine the normal range and the incidences of hypothermia and hyperthermia during the first 24 hours of life in healthy term-born infants nursed according to WHO recommendations. DESIGN: Prospective observational study. SETTING: Norwegian single centre district hospital. Infants were observed during skin-to-skin care or when dressed in cots. PARTICIPANTS: Convenience sample of 951 healthy infants born at term. METHODS: Delivery room temperature was aimed at 26-30°C and rooming-in temperature at 24°C. We measured rectal and room temperatures at 2, 4, 8, 16 and 24 hours of age. MAIN OUTCOME MEASURES: Percentile curves for rectal temperature. Proportions and risk factors for hypothermia and hyperthermia. RESULTS: The mean (SD) room temperature was 24.0°C (1.1), 23.8°C (1.0), 23.8°C (1.0)., 23.7°C (0.9) and 23.8°C (0.9). The median (2.5, 97.5 percentile) rectal temperature was 36.9°C (35.7-37.9), 36.8°C (35.9-37.5), 36.9°C (36.1-37.5), 37.0°C (36.4-37.7) and 37.1°C (36.5-37.7). Hypothermia (<36.5°C) occurred in 28% of the infants, 82% of incidents during the first 8 hours. Risk factors for hypothermia were low birth weight (OR 3.1 (95% CI, 2.0 to 4.6), per kg), male sex, being born at night and nursed in a cot versus skin to skin. Hyperthermia (>37.5°C) occurred in 12% and most commonly in large infants after 8 hours of life. Risk factors for hyperthermia were high birth weight (OR 2.2 (95% CI, 1.4 to 3.5), per kg), being awake, nursed skin to skin and being born through heavily stained amniotic fluid. CONCLUSIONS: Term-born infants were at risk of hypothermia during the first hours after birth even when nursed in an assumed adequate thermal environment and at risk of hyperthermia after 8 hours of age.

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

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

Post-discharge home kangaroo mother care follow-up study in rural Gujarat.

Background: Continuation of kangaroo mother care (KMC) at home is vital for improved infant survival and development. Hence, it is essential to understand potential enablers and barriers to home KMC provision. Methodology: This observational study was conducted in rural Gujarat. KMC was initiated for all low-birth-weight (LBW) neonates during the hospital stay and were advised to continue home KMC on discharge. The mothers of these LBW neonates were interviewed using a structured questionnaire during follow-up visits or via telephone. Results: A total of 100 mothers were interviewed, and 98 practiced home KMC. Mothers' mean age was 24.41 (±3.1) years, and infants' mean age was 3.48 (±1.81) months. The mean weight of neonates at discharge was 1.85 (±0.28) kg. Out of the 104 neonates (96 singleton pregnancies and four twins), 76 (73.07%) were pre-term. 31% mothers provided 4-6 hours of daily KMC. 60% provided KMC for less than 1 hour during each session, while 36% of mothers provided each KMC session for 1-3 hours. 74% of mothers received family support, and 62% faced difficulties in home KMC provision. 88% of mothers were homemakers, and 53% had other children to care for. 51% mothers pre-maturely discontinued KMC provision. 83% of the mothers reported fatigue or pain during KMC provision. Conclusion: Lack of family support, other household responsibilities, and other children to care for were major barriers leading to pre-mature discontinuation of home KMC.

Survival and unique clinical practices of extremely preterm infants born at 22-23 weeks' gestation in Japan: a national survey.

OBJECTIVES: To investigate prognosis and clinical practices of infants born at 22-23 weeks' gestational age (wkGA) in Japan. DESIGN: A national institutional-level electronic questionnaire surveys performed in September 2021. SETTING: All perinatal centres across Japan. PATIENTS: Infants born at 22-23 wkGA in 2018-2020. MAIN OUTCOME MEASURES: Proportion of active resuscitation and survival at neonatal intensive care unit (NICU) discharge, and various clinical practices. RESULTS: In total, 255 of 295 NICUs (86%) responded. Among them, 145 took care of infants born at 22-23 wkGA and answered the questions regarding their outcomes and care. In most NICUs (129 of 145 (89%)), infants born at 22+0 wkGA can be actively resuscitated. In almost half of the NICUs (79 of 145 (54%)), infants born at ≥22+0 wkGA were always actively resuscitated. Among 341 and 757 infants born alive at 22 and 23 wkGA, respectively, 85% (291 of 341) and 98% (745 of 757) received active resuscitation after birth. Among infants actively resuscitated at birth, 63% (183 of 291) and 80% (594 of 745) of infants born at 22 and 23 wkGA survived, respectively. The survey revealed unique clinical management for these infants in Japan, including delivery with caul in caesarean section, cut-cord milking after clamping cord, immediate intubation at birth, hydrocortisone use for chronic lung disease, analgesia/sedation use for infants on mechanical ventilation, routine echocardiography and brain ultrasound, probiotics administration, routine glycerin enema and skin dressing to prevent pressure ulcers. CONCLUSIONS: Many 22-23 wkGA infants were actively resuscitated in Japan and had a high survival rate. Various unique clinical practices were highlighted.

Screening of substance use in pregnancy: A Danish cross-sectional study.

INTRODUCTION: There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women. MATERIAL AND METHODS: In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions. RESULTS: A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use. CONCLUSIONS: Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed.

Analysis of Heart Rate Variability in Newborns Dogs with Different Types of Delivery during the First 35 Days of Life.

The present study aimed to evaluate the influence of the autonomic nervous system on cardiovascular function during the first 35 days of life in different types of delivery, using heart rate variability (HRV) indices. Thirty newborns were equally divided into two groups based on delivery type: eutocic delivery (EG) and emergency cesarean section (CG). Electrocardiographic evaluation was performed at birth (T0), 24 h postpartum (T1), and at 7, 14, 21, 28, and 35 days of life (T2 to T6). Physical parameters, neonatal reflexes, and Apgar scores were recorded. Over 35 days, the values of the time domain indices were higher in the GE group and increased with age. In the frequency domain, the low frequency (LF) index was higher in the CG, and the opposite occurred for the high frequency (HF) index. Since the CG presented lower HRV than the EG, it was shown that the type of delivery should be considered for the assessment of autonomic nervous system activity in neonates. Thus, as predictive factors of vitality, HRV and Apgar scores can help in the face of neonatal depression, demonstrating that delivery by emergency cesarean section can predispose newborns to delays in the autonomic influence on the heart.

Predictive Value of Inflammatory Markers NLR, PLR, APRI, SII, and Liver Function Tests in Systemic Inflammatory Response Syndrome Detection in Full-Term Newborns.

Systemic Inflammatory Response Syndrome (SIRS) is associated with significant morbidity and mortality in full-term newborns. This study aimed to evaluate the predictive value of the Neutrophil-to-Lymphocyte Ratio (NLR), Derived Neutrophil-to-Lymphocyte Ratio (dNLR), Platelet-to-Lymphocyte Ratio (PLR), Neutrophil, Lymphocyte, and Platelet Ratio (NLPR), AST-to-Platelet Ratio Index (APRI), and Systemic Immune-Inflammation Index (SII) in identifying the risk for SIRS development in full-term newborns. Conducted between January 2023 and January 2024, this observational cohort study compared full-term newborns diagnosed with SIRS with newborns without SIRS, measuring the inflammatory markers within the first day of life and three days post-birth. The study included 229 newborns, 81 with SIRS and 148 controls without SIRS. Statistically significant differences were observed in NLR (3.81 vs. 2.20, p < 0.0001), PLR (68.12 vs. 52.30, p < 0.0001), and liver enzymes (AST 40.96 U/L vs. 31.58 U/L, ALT 34.66 U/L vs. 22.46 U/L, both p < 0.0001) between the groups. The NLPR demonstrated substantial diagnostic value, with a sensitivity of 78.36% and specificity of 83.52% at 72 h (p < 0.0001). Regression analysis highlighted that the NLPR and SII were strongly predictive of SIRS, with the NLPR showing over three-times higher SIRS risk (HR 3.29, p < 0.0001) and SII indicating nearly 3.5 times the risk (HR 3.47, p < 0.0001). The NLPR, APRI, and SII showed similar prediction values to CRP levels measured on the first and third days of life (HR 3.16). Inflammatory markers like NLR, PLR, and systemic indices such as NLPR and SII, alongside liver function tests, are significant predictors of SIRS in full-term newborns. These findings support the integration of these markers into routine neonatal care, allowing for early identification and potentially improved management of newborns at risk for SIRS, thereby enhancing clinical outcomes.

[L'Atelier créa: a therapeutic mediation group for neonatal parents]. / L'Atelier créa : un groupe thérapeutique à médiation pour les parents en néonatalogie.

The parents of a baby hospitalized in a neonatal unit are confronted with the trauma of premature birth. L'Atelier créa, a creatively-mediated peer group, was designed to give them a space in which to meet and share their experiences. It's a time for talking, imagining and dreaming about the baby. This group is also a form of passage, taking the place of ritual, allowing access to the parent-baby triad, in this sometimes so inhospitable universe.

Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. INTERVENTIONS: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). MAIN OUTCOME MEASURES: Mortality and meningitis. RESULTS: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. CONCLUSIONS: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

Timing and dosage of intrapartum prophylactic penicillin for preventing early-onset group B streptococcal disease: assessing maternal and umbilical cord blood concentration.

OBJECTIVE: Timing of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin concentrations in mothers and infants at birth in relation to time elapsed from administration to delivery and to the minimal inhibitory concentration (MIC) for GBS. MAIN OUTCOME MEASURES: Penicillin G concentrations in maternal and umbilical cord blood in relation to time and dose from administration to time of delivery. RESULTS: In 44 mother-infant dyads, median maternal penicillin G concentration was 0.2 mg/L (IQR 0-0.8 mg/L; range 0-1.6 mg/L). Median infant penicillin G concentration was 1.2 mg/L (IQR 0.5-5.0 mg/L; range 0-12.7 mg/L). In all infants (N=38) born less than 4 hours after the latest IAP administration, penicillin G concentrations far exceeded MIC (0.125 mg/L), even after short time intervals between IAP administration and birth. The highest plasma concentrations were reached in umbilical cord blood within 1 hour from IAP administration to birth.For 44 mother-infant dyads, maternal concentrations were very low compared with their infants'; particularly, very high concentrations were seen in the 20 infants with only one dose of IAP. CONCLUSION: High concentrations of penicillin G were found in umbilical cord blood of infants born less than 4 hours after IAP administration, well above the MIC for GBS.

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.

Scandinavian perspectives on life support at the border of viability.

Advances in neonatal medicine have allowed us to rescue extremely preterm infants. However, both long-term vulnerability and the burden of treatment in the neonatal period increase with decreasing gestational age. This raises questions about the justification of life support when a baby is born at the border of viability, and has led to a so-called "grey zone", where many professionals are unsure whether provision of life support is in the child's best interest. Despite cultural, political and economic similarities, the Scandinavian countries differ in their approach to periviable infants, as seen in their respective national guidelines and practices. In Sweden, guidelines and practice are more rescue-focused at the lower end of the border of viability, Danish guidelines emphasizes the need to involve parental views in the decision-making process, whereas Norway appears to be somewhere in between. In this paper, I will give an overview of national consensus documents and practices in Norway, Sweden and Denmark, and reflect on the ethical justification for the different approaches.

The Potential of Fecal Volatile Organic Compound Analysis for the Early Diagnosis of Late-Onset Sepsis in Preterm Infants: A Narrative Review.

Early diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future.

Early Postnatal Administration of Erythropoietin and Its Association with Neurodevelopmental Outcomes and Incidence of Intraventricular Hemorrhage and Hypoxic-Ischemic Encephalopathy: A Four-Week Observational Study.

This study aimed to investigate the impact of early erythropoietin (EPO) administration on the neurodevelopment of newborns, specifically focusing on its effects on hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH). The primary objective was to determine whether early EPO administration could impact the short-term neurodevelopmental outcomes and provide safety in neonates at risk for neurodevelopmental disorders. Conducted at the "Louis Turcanu" Children's Emergency Clinical Hospital in Timisoara, Romania, this observational study included 121 neonates receiving EPO and 130 No EPO controls. EPO was administered within the first 48 h of life, with doses of 1000 U/kg that escalated to 2000 U/kg if necessary. Besides observing the occurrence of IVH and HIE, this study measured clinical and biochemical markers, including LDH, blood glucose, urea, creatinine, CPK, CRP, PCT, and erythropoietin levels alongside hematology and coagulation profiles. There were no significant differences in baseline characteristics between the groups. The EPO group showed significant reductions in LDH levels from days 1-3 to 7-10 (695.0 U/L to 442.0 U/L) and the APTT value (54.0 s) compared with the No EPO group (38.0 s). Notably, early EPO administration was associated with a significant decrease in HIE severity (beta coefficient: -0.38, p = 0.001). Additionally, lower gestational ages and hemoglobin levels correlated with increased severity of HIE. By week four, there was a significant reduction in moderate and severe HIE cases in the EPO group compared with controls (p = 0.001). Early administration of EPO in neonates significantly reduced the severity of IVH and HIE, suggesting its potential as a neuroprotective agent in neonatal care.

Necrotizing enterocolitis in monochorionic twins: Insights from an identical twin model.

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study is to evaluate risk factors for NEC using an identical twin model. In this case-control study, all monochorionic twin pairs born in our center in 2002-2020 were retrospectively reviewed for NEC. Potential risk factors for NEC were studied. For within-pair comparison, outcomes were compared between affected and unaffected twins. Within-pair analyses showed that the twin with NEC had a lower birth weight compared to its unaffected co-twin (1100 (913-1364) vs. 1339 (1093-1755) grams). Median gestational age at birth and birth weight were lower in twin pairs in the NEC-group compared to the no-NEC group, 29.1 weeks (27.8-30.8) versus 33.6 (30.7-36.0) and 1221 g (1010-1488) versus 1865 (1356-2355) respectively. Twin pregnancies in the NEC-group were more often complicated by twin-to-twin transfusion syndrome compared to the no-NEC-group (70 % (14/20) vs. 49 % (472/962)), particularly when treated with amnioreduction. This unique population of identical twins confirms that preterm neonates with a relatively lower birth weight are more prone to develop NEC compared to their co-twin, regardless of other genetic, maternal and obstetrical factors.

Implications of Ad-Hoc Molecular Typing for Infection Control Measures in a Multi-cluster, Multi-phenotypic Serratia marcescens Outbreak in a Neonatal Intensive Care Unit.

INTRODUCTION: Serratia marcescens is known to cause outbreaks in Neonatal Intensive Care Units (NICU). Traditionally epidemiological data, antimicrobial resistance patterns and epidemiological typing are being used to guide infection prevention methods. Whole genome sequencing (WGS) applications such as core-genome multi-locus sequence typing (cgMLST) applied during an outbreak would potentially give more detailed information on the source and spread of bacteria enabling more efficient control measures. CgMLST was used during an S. marcescens outbreak at a NICU. METHODS: Neonates admitted to the NICU of the Leiden University Medical Center (LUMC) during an outbreak between September 2023-January 2024, with S. marcescens being cultured were included. Environmental samples were taken to search for a common source, antibiotic susceptibility testing was performed, and antimicrobial resistances genes were analysed. RESULTS: S. marcescens strains from 17 of the 20 positive patients were available for molecular typing. The cgMLST scheme revealed five different complex types consisting of four separate clusters. Multiple clusters made an unidentified persistent environmental source as cause of the outbreak less likely, leading to a quick downscaling of infection prevention measures. Differences were shown in aminoglycoside resistance patterns of isolates within the same complex types and patients. DISCUSSION: The use of ad-hoc cgMLST provided timely data for rational decision making during an S. marcescens outbreak at the NICU. Antibiotic phenotyping alone was found not to be suitable for studying clonal spread during this outbreak with S. marcescens.

Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.