Correction: An eight-year follow-up on auditory outcomes after neonatal hearing screening.

[This corrects the article DOI: 10.1371/journal.pone.

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.

An eight-year follow-up on auditory outcomes after neonatal hearing screening.

Objective: The aim of this study is to assess the neonatal click Auditory Brainstem Response (ABR) results in relation to the subsequently determined mean hearing loss (HL) over 1, 2 and 4 kHz, as well as over 2 and 4 kHz.

Methods: Between 2004-2009, follow-up data were collected from Visual Reinforcement Audiometry (VRA) at 1 and 2 years and playaudiometry at 4 and 8 years of newborns who had failed neonatal hearing screening in the well-baby clinics and who had been referred to a single Speech and Hearing center. Hearing Level data were compared with ABR threshold-levels established during the first months of life.

Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation.

Objective: Concerns have been raised about the effect of skin color on the accuracy of transcutaneous bilirubin (TcB) measurements, a widely used method for hyperbilirubinemia diagnosis in newborns. Literature is inconclusive, with both reported under- and overestimations of the TcB with increasing skin pigmentation. Therefore, the influence of skin color on TcB measurements was systematically evaluated in a controlled, in vitro setting.

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.

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.

Quantification of cephalocaudal progression of jaundice in preterm infants.

Background: The cephalocaudal progression (CCP) of neonatal jaundice is a well-known phenomenon, but quantitative information on CCP in preterm infants is absent. In this study, CCP was quantified in preterm infants as a function of postnatal age and body location.

Methods: 5.

Postnatal corticosteroid response in neonates < 32 weeks and relation with placental pathology.

Unlabelled: Acute chorioamnionitis and maternal vascular malperfusion are associated with an increased risk of bronchopulmonary dysplasia. To prevent bronchopulmonary dysplasia, postnatal corticosteroids are given to preterm neonates. Clinical observations indicate not all neonates respond to corticosteroids, the so-called non-responders.

Short-term pulmonary and systemic effects of hydrocortisone initiated 7-14 days after birth in ventilated very preterm infants: a secondary analysis of a randomised controlled trial.

Objective: Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week.

Design: Randomised placebo-controlled trial.

Irradiance footprint of phototherapy devices: a comparative study.

Background: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e.

Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy.

The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age.

Inter-device reproducibility of transcutaneous bilirubin meters.

Background: Transcutaneous bilirubinometry is a widely used screening method for neonatal hyperbilirubinemia. Deviation of the transcutaneous bilirubin concentration (TcB) from the total serum bilirubin concentration (TSB) is often ascribed to biological variation between patients, but variations between TcB meters may also have a role. This study aims to provide a systematic evaluation of the inter-device reproducibility of TcB meters.

Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation: Outcome at 2 Years.

Objective: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability.

Study Design: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age.

Maturation of the auditory system in normal-hearing newborns with a very or extremely premature birth.

Background: Literature shows that lower gestational age leads to greater delays in the auditory conduction, which suggests atypical maturation of the brainstem in normal-hearing premature newborns. Our aim is to investigate if there is a difference between the extrauterine and intrauterine maturation of the auditory system in normal-hearing newborns with a very premature (28-31 weeks) or extremely premature (<28 weeks) birth.

Methods: Results of the Automated Auditory Brainstem Response Newborn Hearing Screening Program in Dutch Neonatal Intensive Care Units and diagnostic examinations were centrally registered from 1998 to 2016.

[Rotavirus infections in neonates: not as innocent as expected].

Background: Rotavirus is a common cause of gastroenteritis in children. It is much less known that rotavirus infections can lead to encephalitis with convulsions in neonates.

Case Description: A premature boy (36 weeks + 5 days) developed neonatal convulsions 17 days post-partum.

Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.

Aims: Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use.

Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia.

Background: Phenobarbital and midazolam are commonly used drugs in (near-)term neonates treated with therapeutic hypothermia for hypoxic-ischaemic encephalopathy, for sedation, and/or as anti-epileptic drug. Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate. Therefore, co-treatment with phenobarbital might impact midazolam clearance.

Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial.

Objective: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI.

Study Design: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured.

Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.

Objective: Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.

Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis.

Background: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis.

Objectives: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis.

Methods: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.

Brain imaging can predict neurodevelopmental outcome of Group B streptococcal meningitis in neonates.

Aim: The association between cranial ultrasound (CUS) or magnetic resonance imaging (MRI) lesions and neonatal Group B streptococcal (GBS) meningitis outcome has not been studied in detail.

Methods: This retrospective study assessed CUS, cranial MRI and neurodevelopmental outcome in 50 neonates with GBS meningitis admitted to three neonatal intensive care units in the Netherlands between 1992 and 2014. Death, cognitive outcome and motor outcome below -1 SD were considered as adverse outcomes.

Evaluation of a System-Specific Function To Describe the Pharmacokinetics of Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia.

The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as they have been unknown until now.

Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

Objective: To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an "early approach" (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a "late approach" (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention.

Methods: Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound.

DOSE EVALUATION FOR DIGITAL X-RAY IMAGING OF PREMATURE NEONATES.

X-ray radiography is a commonly used diagnostic method for premature neonates. However, because of higher radiosensitivity and young age, premature neonates are more sensitive to the detrimental effects of ionising radiation. Therefore, it is important to monitor and optimise radiation doses at the neonatal intensive care unit (NICU).