RISEinFAMILY project: the integration of families at neonatal intensive care units (NICUs) to empower them as primary caregivers: study protocol for a stepped wedge cluster controlled trial.

BACKGROUND: Family Integrated Care (FICare) has demonstrated positive outcomes for sick neonates and has alleviated the psychological burden faced by families. FICare involves structured training for professionals and caregivers along with the provision of resources to offer physical and psychological support to parents. However, FICare implementation has been primarily limited to developed countries. It remains crucial to assess the scalability of this model in overcoming social-cultural barriers and conduct a cost-effectiveness analysis. The RISEinFAMILY project aims to develop an adapted FICare model that can serve as the international standard for neonatal care, accommodating various cultural, architectural, and socio-economic contexts. METHODS: RISEinFAMILY is a pluri-cultural, stepped wedge cluster controlled trial conducted in Spain, Netherlands, the UK, Romania, Turkey, and Zambia. Eligible participants include infant-family dyads admitted to the Neonatal Intensive Care Unit (NICU) requiring specialised neonatal care for a minimum expected duration of 7 days, provided there are no comprehension barriers. Notably, this study will incorporate a value of implementation analysis on FICare, which can inform policy decisions regarding investment in implementation activities, even in situations with diverse data. DISCUSSION: This study aims to evaluate the scalability and adaptation of FICare across a broader range of geographical and sociocultural contexts and address its sustainability. Furthermore, it seeks to compare the RISEinFAMILY model with standard care, examining differences in short-term newborn outcomes, family mental health, and professional satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov NCT06087666. Registered on 17 October 2023. PROTOCOL VERSION: 19 December 2022; version 2.2.

Predictive performance of multiple organ dysfunction in asphyxiated newborns treated with therapeutic hypothermia on 24-month outcome: a cohort study.

BACKGROUND: Perinatal asphyxia may be followed by multiple organ dysfunction (MOD) and is often included in prognostication of the individual patient, but evidence of discriminating accuracy is lacking. The aim of this study was to assess whether MOD in asphyxiated neonates during therapeutic hypothermia (TH) predicts mortality or neurodevelopmental impairment (NDI) at 24 months of age and which peripartum variables are associated with the onset of MOD. METHODS: A retrospective analysis of a prospective cohort study of asphyxiated newborns undergoing TH was performed. MOD was defined as dysfunction of the brain (encephalopathy) combined with two or more organ systems. Outcome was routinely assessed by standardised developmental testing at the age of 24 months. The predictive accuracy of MOD on the combined outcome and its components (death and NDI) was expressed as areas under the receiver operating characteristic curves (AUROCs). The associations of peripartum variables and development of MOD were expressed as ORs and their CIs. RESULTS: 189 infants (median gestation 40 (range 36-42 weeks) with moderate to severe hypoxic ischaemic encephalopathy were included. 47% developed MOD. The prediction of the combined 24-month outcome or its components showed AUROCs <0.70. Associated with MOD were pH at birth (OR 0.97, CI 0.95 to 0.99), lactate at birth (OR 1.09, CI 1.04 to 1.15), Base Excess (BE) at birth (OR 0.94, CI 0.90 to 0.99) and epinephrine administration during resuscitation (OR 2.09, CI 1.02 to 4.40). CONCLUSION: MOD has a low discriminating accuracy in predicting mortality or NDI at 24 months age and might not be useful for prognostication. Signs of acid-base disturbance and adrenalin use at birth are associated with the development of MOD.

A systematic review comparing neurodevelopmental outcome in term infants with hypoxic and vascular brain injury with and without seizures.

BACKGROUND: There is increasing evidence that neonatal seizures in term neonates with stroke, asphyxia or brain haemorrhage might be associated with adverse neurodevelopment and development of epilepsy. The extent of this association is not known. The objective of this study was to assess the possible impact of neonatal seizures on these outcomes and if possible calculate a relative risk. METHODS: A systematic review and meta-analysis was performed (study period January 2000-June 2015). PubMed, Medline and Embase were searched for cohort studies evaluating neurodevelopmental outcome at the age of at least 18 months or development of epilepsy in surviving term neonates with or without neonatal seizures. The methodological quality of included studies was assessed and data extractions were performed in a standardized manner by independent reviewers. Pooled Relative Risks (RR) with 95% confidence intervals for adverse outcome were calculated if possible. RESULTS: Out of 1443 eligible studies 48 were selected for full text reading leaving 9 cohort studies for the final analyses (4 studies on stroke, 4 on perinatal asphyxia and one on cerebral hemorrhage). For all cases with stroke or asphyxia combined the pooled risk ratio (RR) for adverse outcome when suffering neonatal seizures was 7.42 (3.84-14.34); for neonates with perinatal asphyxia: 8.41 (4.07-17.39) and for neonates with stroke: 4.95 (1.07-23.0). The pooled RR for development of late onset epilepsy could only be determined for infants suffering from stroke: 1.48 (0.82-2.68). Results were biased and evidence sparse. CONCLUSIONS: The presence of neonatal seizures in term newborns with vascular or hypoxic brain injury may have an impact on or be a predictor of neurodevelopmental outcome. The biased available data yield insufficient evidence about the true size of this association.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

OBJECTIVE: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. METHODS: This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. RESULTS: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). CONCLUSION: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Very preterm born children at early school age: Healthcare therapies and educational provisions.

AIM: To explore changes in motor and cognitive outcomes in very preterm (VP; gestational age<30weeks) born children between ages five and six years, and to determine whether changes in these outcomes were associated with the use of healthcare therapies and educational provisions. STUDY DESIGN: Single-center observational cohort study. Five-year-old VP born children of a one-year-cohort of our neonatal follow-up program (N=90) were invited for re-assessments at age six. Use of healthcare therapies and educational provisions was registered at ages five and six years. Motor function (Movement Assessment Battery for Children-2 [M-ABC-2]; higher scores indicate better functioning) and IQ (Wechsler Preschool and Primary Scale for Intelligence [WPPSI-III-NL]) were assessed at both ages. RESULTS: Sixty-four VP born children were seen at ages five and at six years. In this year, 61% received healthcare therapies and/or educational provisions. M-ABC-2 scores of VP born children who received healthcare therapy and/or educational provisions were significantly higher (M=8.9 [SD=3.2]) at age six years than at age five years (M=7.5 [SD=3.3]); p<0.00). M-ABC-2 scores remained stable in the average range in VP born children without any support. IQ scores remained stable irrespective of received support. CONCLUSIONS: Improvements in motor outcomes are associated with the use of healthcare therapies and/or educational support between ages five and six years in VP born children. Future studies need to determine the efficacy of existing interventions, and to develop tailored interventions to support VP born children in the transfer period from preschool to primary education.

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia.

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.

[Infection with human parvovirus B19 ('fifth disease') during pregnancy: potential life-threatening implications for the foetus]. / Infectie met het Humaan parvovirus B19 ('vijfde ziekte') in de zwangerschap: voor de foetus soms levensbedreigend.

Four pregnant women, aged 29, 32, 36 and 36 years, respectively, were diagnosed with Human parvovirus B19 (B19V) infection. Only the first woman had exanthema and fever. In the first three cases, the source of infection appeared to be another child; two of these children were infected during a school outbreak. All four foetuses were infected, but the first foetus was asymptomatic and healthy at birth. The second foetus had anaemia and increased blood flow in the middle cerebral artery; it received an intrauterine transfusion and was healthy at birth. The third foetus was almost immobile and had cardiomegaly and hydrops fetalis; it was dead upon induced birth. In the fourth case, pregnancy was uneventful until two days before parturition, when the mother reported a decrease in foetal movement. The infant was born and developed respiratory insufficiency after 8 hours. Imaging revealed multiple bilateral lesions in frontal, occipital and parietal white matter consistent with infarction. The infant died after 5 days. Infection with B19V is associated with a wide range of clinical presentations and outcomes. Effects may range from an uncomplicated pregnancy to severe hydrops fetalis or intrauterine foetal death. Maternal symptoms may be aspecific, which complicates early diagnosis. When maternal B19V infection is suspected, immediate investigation for recent B19V infection should be performed. Quantitative B19 viral load measurements may provide insight into the stage of infection and may guide foetal monitoring. Referral to a foetal therapy unit is essential for hydrops fetalis or severe foetal anaemia. Intrauterine transfusion with erythrocytes significantly improves foetal outcome. Despite a successful transfusion procedure, long-term neurodevelopment may be affected, and developmental follow up is advised.

A case of neonatal dural sinus malformation: clinical symptoms, imaging and neuropathological investigations.

We report a case of neonatal dural sinus malformation already visible on antenatal ultrasound. This is a rare disease entity in infants and children. Clinical diagnosis was made by demonstrating a cranial murmur on auscultation; macrocrania and signs of progressive cardiac failure. Imaging studies as cerebral ultrasound, postnatal MRI scan and MR angiography demonstrated a large dural sinus malformation originating from the sagittal sinus with extensive arteriovenous fistulae. Due to the extent of the lesion, the existing ischemic brain damage and involvement of the torcular, no therapeutic options were available and the child died of irreversible cardiac failure. The diagnosis was confirmed with autopsy. We discuss the clinical presentation, imaging and neuropathological results and relate our findings to embryological data and the existing literature.

Thrombocytopenia in hydropic fetuses with parvovirus B19 infection: incidence, treatment and correlation with fetal B19 viral load.

OBJECTIVE: To examine (1) the incidence of fetal thrombocytopenia in hydropic fetuses with congenital B19 virus infection, (2) the effect of intrauterine platelet transfusions and (3) the correlation between fetal B19 viral load and severity of thrombocytopenia. DESIGN: Retrospective analysis of data from prospectively collected fetal blood samples. SETTING: Leiden University Medical Centre, the national centre for management of intrauterine fetal disease in the Netherlands. POPULATION: Thirty hydropic fetuses treated with intrauterine red blood cell and platelet transfusions for human B19 virus-induced severe fetal anaemia and thrombocytopenia over a 10-year period. METHODS: Fetal blood samples (n= 30) taken before and after intrauterine transfusion were investigated. No cases were excluded, and there was no loss to follow up. MAIN OUTCOME MEASURES: Parameters recorded were gestational age, experienced fetal movements, gravidity and parity, severity of fetal hydrops, severity of fetal anaemia and thrombocytopenia and megakaryocyte and reticulocyte counts. Survival and procedure-associated complications were documented. Quantitative B19 viral load measurements were performed on all fetal samples. RESULTS: Forty-six percent of all hydropic fetuses showed severe thrombocytopenia. No antenatal intracerebral haemorrhage or procedure-associated bleeding occurred. Overall, survival was 77%. Platelet counts increased following platelet transfusion and decreased significantly following red blood cell transfusion alone. No correlation was found between fetal viral loads and platelet counts. CONCLUSION: Thrombocytopenia was frequently encountered in fetal B19V infection, but fetal bleeding complications were not noted. Absence of a direct relationship between fetal B19 viral load and platelet counts suggests a temporal dissociation between these findings. Dilutional thrombocytopenia is frequently seen in the fetus following red blood cell transfusion alone. The clinical significance of this phenomenon is unclear. The risk of fluid overload by fetal platelet transfusion in a severely hydropic fetus should be weighed against the low incidence of fetal bleeding complications.

Unilateral submandibular suppurative sialadenitis in a premature infant.

UNLABELLED: Isolated submandibular suppurative sialadenitis is extremely rare in newborn infants and is associated with prematurity and prolonged gavage feeding. This report describes a premature infant who developed a life-threatening airway obstruction due to suppurative submandibular sialadenitis. The diagnosis was made on clinical grounds and confirmed by ultrasonography. Staphylococcus aureus was grown from the pus expressed from the Wharton's duct orifice. Upper airway obstruction and respiratory failure were managed with intubation and mechanical ventilation, and the sialadenitis resolved quickly and completely with flucloxacillin treatment. Possible causes of sialadenitis include dehydration, decreased saliva flow and stasis during gavage feeding, duct obstruction by stones and direct bacterial inoculation. Ultrasonography is the diagnostic imaging of choice to exclude congenital tumours, lymphadenitis, congenital malformations of the Wharton's duct or the gland itself, and subcutaneous fat necrosis. CONCLUSION: Early diagnosis and antibiotic treatment of suppurative submandibular sialadenitis may prevent complications such as abscess formation, septicaemia and respiratory failure.