Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.

Necrotizing enterocolitis (NEC) is a relatively rare but very severe gastrointestinal disease primarily affecting very preterm infants. NEC is characterized by excessive inflammation and ischemia in the intestines, and is associated with prolonged, severe visceral pain. Despite its recognition as a highly painful disease, current pain management for NEC is often inadequate, and research on optimal analgesic therapy for these patients is lacking.

Assessing neonatal Sequential Organ Failure (nSOFA) scores in suspected late-onset neonatal sepsis among preterm infants: implications for morbidity and mortality.

Background: The neonatal Sequential Organ Failure Assessment (nSOFA) score is an organ dysfunction score developed for predicting mortality risk in preterm neonates with proven late-onset neonatal sepsis (LONS) and necrotising enterocolitis. However, the utility of the nSOFA score in determining the risk of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) or mortality in patients with suspected LONS is unknown.

Methods: We performed a dual-centre retrospective cohort study of preterm (gestational age <32 weeks) neonates suspected of LONS, from 2016 to 2020 at two neonatal intensive care units.

Caffeine therapy for apnea of prematurity: single center study on dosing practices and perceived effectiveness.

Introduction: Caffeine is the registered pharmacologic treatment for apnea of prematurity and is extensively used in the neonatal intensive care units (NICUs) based on evidence from randomized controlled trials. This study aimed to describe the clinical use of caffeine based on real-world data, hypothesizing a divergence from the registered dosing regimen.

Methods: A retrospective analysis included infants born before 30 weeks of gestation, admitted to the NICU of the Erasmus MC Rotterdam from 2018 to 2021.

Repetitive daily oxytocin treatment reduces weight gain but not acute neonatal procedural pain.

Background: While the incidence of neonatal intensive care unit (NICU) admission steadily increases, neonatology lacks evidence of a safe, effective, and preventive analgesic for treating procedural pain. Given its role in nociception and promoting healthy neurodevelopment, the endogenous neuropeptide oxytocin (OT) emerges as a promising candidate.

Methods: This study investigates the use of daily repeated subcutaneous OT (1 mg/kg) treatment in an established model of neonatal repetitive procedural pain and assesses the effectivity of OT treatment on mechanical sensitivity and body weight.

Parents in Neonatal Pain Management-An International Survey of Parent-Delivered Interventions and Parental Pain Assessment.

Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions.

Methods: A web-based survey was distributed to neonatal units worldwide.

Neonatal Clinical Pharmacology.

Similar to other populations, care of neonates strongly relies on robust guidance on neonatal pharmacotherapy, covering an age-appropriate drug formulation, an individualized dose, and information on its efficacy and safety for a specific indication in this population, preferably weighted to alternative approaches [...

Current anesthesia practice for preterm infants undergoing surgery for necrotizing enterocolitis: A European survey.

Study Objective: Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these patients is challenging, due to their prematurity and critical illness with hemodynamic instability. Currently, there are no guidelines for anesthetic care for these vulnerable patients.

When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers?

Aims: Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs.

Population pharmacokinetics of vancomycin in term neonates with perinatal asphyxia treated with therapeutic hypothermia.

Aims: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment.

Methods: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study.

Repetitive neonatal procedural pain affects stress-induced plasma corticosterone increase in young adult females but not in male rats.

Exposure to repetitive painful procedures in the neonatal intensive care unit results in long-lasting effects, especially visible after a "second hit" in adulthood. As the nociceptive system and the hypothalamic-pituitary-adrenal (HPA) axis interact and are vulnerable in early life, repetitive painful procedures in neonates may affect later-life HPA axis reactivity. The first aim of the present study was to investigate the effects of repetitive neonatal procedural pain on plasma corticosterone levels after mild acute stress (MAS) in young adult rats.

Biomarkers for assessing pain and pain relief in the neonatal intensive care unit.

Newborns admitted to the neonatal intensive care unit (NICU) regularly undergo painful procedures and may face various painful conditions such as postoperative pain. Optimal management of pain in these vulnerable preterm and term born neonates is crucial to ensure their comfort and prevent negative consequences of neonatal pain. This entails accurate and timely identification of pain, non-pharmacological pain treatment and if needed administration of analgesic therapy, evaluation of treatment effectiveness, and monitoring of adverse effects.

Global cross-sectional survey on neonatal pharmacologic sedation and analgesia practices and pain assessment tools: impact of the sociodemographic index (SDI).

Background: There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress.

Methods: This was a global, prospective, cross-sectional study.

Predictive Performance of a Gentamicin Pharmacokinetic Model in Term Neonates with Perinatal Asphyxia Undergoing Controlled Therapeutic Hypothermia.

Background: Model validation procedures are crucial when population pharmacokinetic (PK) models are used to develop dosing algorithms and to perform model-informed precision dosing. We have previously published a population PK model describing the PK of gentamicin in term neonates with perinatal asphyxia during controlled therapeutic hypothermia (TH), which showed altered gentamicin clearance during the hypothermic phase dependent on gestational age and weight. In this study, the predictive performance and generalizability of this model were assessed using an independent data set of neonates with perinatal asphyxia undergoing controlled TH.

Vascular reactivity is altered in the placentas of fetuses with congenital diaphragmatic hernia.

Introduction: Infants with congenital diaphragmatic hernia (CDH) often develop pulmonary hypertension but frequently fail to respond to vasodilator therapy, for instance because of an altered pulmonary vasoreactivity. Investigating such alterations in vivo is impossible. We hypothesised that these alterations are also present in fetoplacental vessels, since both vasculatures are exposed to the same circulating factors (e.

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial).

Background: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome.

Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.

Background: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs.

Maturation of Paracetamol Elimination Routes in Preterm Neonates Born Below 32 Weeks of Gestation.

Purpose: Despite being off-label, intravenous paracetamol (PCM) is increasingly used to control mild-to-moderate pain in preterm neonates. Here we aim to quantify the maturation of paracetamol elimination pathways in preterm neonates born below 32 weeks of gestation.

Methods: Datasets after single dose (rich data) or multiple doses (sparse data) of intravenous PCM dose (median (range)) 9 (3-25) mg/kg were pooled, containing 534 plasma and 44 urine samples of PCM and metabolites (PCM-glucuronide, PCM-sulfate, PCM-cysteine, and PCM-mercapturate) from 143 preterm neonates (gestational age 27.

Diversity of Parent Emotions and Physician Responses During End-of-Life Conversations.

Background And Objectives: To provide support to parents of critically ill children, it is important that physicians adequately respond to parents' emotions. In this study, we investigated emotions expressed by parents, physicians' responses to these expressions, and parents' emotions after the physicians' responses in conversations in which crucial decisions regarding the child's life-sustaining treatment had to be made.

Methods: Forty-nine audio-recorded conversations between parents of 12 critically ill children and physicians working in the neonatal and pediatric intensive care units of 3 Dutch university medical centers were coded and analyzed by using a qualitative inductive approach.

The influence of intensive care treatment in infancy on cortisol levels in childhood and adolescence.

Background: Infants admitted to the intensive care unit experience numerous early-life stressors, which may have long-term effects on hypothalamic-pituitary-adrenal axis functioning.

Aims: To determine the effects of intensive care treatment and related exposure to stress, pain, and opioids in infancy on cortisol levels in childhood and adolescence.

Study Design: Cross-sectional study.

Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates.

Background: The aim of this study was to investigate the association between inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)) and sepsis severity (neonatal-Sequential-Organ-Failure-Assessment (nSOFA)) and neurodevelopmental outcomes at 2 years, among very preterm neonates.

Methods: Data on preterm neonates (gestational age <30 weeks) from 2016 until 2020 were reviewed. Outcomes of interest were NDI (no, mild, severe) and the motor and cognitive score on the Dutch-Bayley-Scales-of-Infant-and-Toddler-Development (Bayley-III-NL) assessed at the corrected age of 2 years.

Sedation Prior to Intubation at Birth in Infants with Congenital Diaphragmatic Hernia: An International Survey on Current Practices.

Introduction: Infants with congenital diaphragmatic hernia (CDH) are commonly intubated immediately after birth. Consensus on whether to provide sedation prior to intubation in the delivery room is lacking, although avoidance of stress is especially important in this population with high risk of pulmonary hypertension. We aimed at obtaining an overview of local pharmacological interventions and at providing guidance on delivery room management.

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia.

Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study.