Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study.

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO2) 10-13 kPa and peripheral oxygen saturation (SpO2) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34-0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 was < 92% in 169/181 (93%) infants for 1.6% (0.5-4.3%) of the iNO time.    Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range.

Efficacy of Levetiracetam as Add-On Therapy in the Treatment of Seizures in Neonates.

INTRODUCTION: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment. METHODS: Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated. RESULTS: A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36-44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration. DISCUSSION: Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration.

Feasibility of neurosonography in CHD-fetuses and controls in a clinical tertiary setting.

Objective: Ultrasonographic examination is the first-tier test to detect abnormal development of central nervous system (CNS). In optimal conditions, neurosonography can detect all important hallmarks of CNS development. It is, however, not known how the performance of this modality is in a routine setting. We aimed to evaluate the feasibility of neurosonography in a time-limited routine setting. Study design: We have performed a prospective study in which we have included a group of pregnant women carrying a fetus with an isolated congenital heart defect (CHD), and a control group of fetuses without structural anomalies. We have performed basic neurosonography examination according to the guideline 'how to perform a basic screening examination of the CNS', published by the international society of ultrasound in obstetrics and gynecology in both groups. In all these examinations, 9 brain structures were scored in 3 different planes, by researchers that were blinded for group allocation. A sufficient neurosonogram was performed when 7 or more out of 9 CNS structures were clearly visible during the off-line scoring of the examination. Results: A total of 574 neurosonographic examinations were performed in 151 fetuses, 90 in the CHD-group and 61 in the control group. A sufficient neurosonogram could be performed in 79% (234/294) of cases in a clinical setting (CHD cases) and in 90% (253/280) of control pregnancies. Higher maternal BMI (>30), maternal age, fetal cephalic position, fetal gender and placental position did not significantly influence neurosonography scores. Conclusion: In clinical setting, basic fetal neurosonography can be sufficiently performed in the majority of cases. This was not significantly influenced by maternal or fetal factors. The optimal gestational age for neurosonography is between 22 and 34 weeks.

Early red blood cell transfusion and the occurrence of intraventricular hemorrhage in very preterm infants.

BACKGROUND: Preterm infants are at risk of developing both intraventricular hemorrhage (IVH) and anemia of prematurity. Several studies reported an association between early postnatal red blood cell (RBC) transfusion and IVH, however the timing and causality between these two remains unclear. AIMS: To describe the temporal sequence between administration of early RBC transfusion (within the first week of life) and diagnosis of IVH in very preterm infants. STUDY DESIGN: Retrospective single center case-series. SUBJECTS: 132 very preterm infants (<32 weeks' gestation), admitted to a level III neonatal intensive care unit, studied with serial cranial ultrasound (CUS), and diagnosed with any grade of IVH. OUTCOME MEASURES: Number and timing of early RBC transfusions in relation to the timing of IVH. RESULTS: Median time of IVH diagnosis was 20.5 h after birth (interquartile range [IQR], 6.25-49.00 h). Of those who received an early RBC transfusion (36 %, 47/132), only 15 % (20/132) received it before the IVH diagnosis. Infants with RBC transfusion before IVH more frequently had lower birth weight, received less fequently antenatal steroids, required more often invasive mechanical ventilation and surfactant administration, had more often hypo- and hypercapnia, and received more fluid boluses, NaHCO3, and inotropes compared to the rest. CONCLUSIONS: In the majority of infants, IVH was already present at the time of the first RBC transfusion. Studies including pre- and post RBC transfusion CUS are needed to assess the effect of early RBC transfusions on the development of IVH in preterm neonates.

Most major bleeds in preterm infants occur in the absence of severe thrombocytopenia: an observational cohort study.

OBJECTIVE: To describe the incidence of major bleeds according to different platelet counts in very preterm infants, and to explore whether this association is influenced by other risk factors for bleeding. DESIGN: Observational cohort study. SETTING: A Dutch tertiary care neonatal intensive care unit. PATIENTS: All consecutive infants with a gestational age at birth <32 weeks admitted between January 2004 and July 2022. EXPOSURE: Infants were stratified into nine groups based on their nadir platelet count (×109/L) during admission (<10, 10-24, 25-49, 50-99, 100-149, 150-199, 200-249, 250-299 and ≥300), measured before the diagnosis of a major bleed and before any platelet transfusion was administered. MAIN OUTCOME MEASURE: Incidence of major bleeds during admission. Logistic regression analysis was used to quantify the relationship between nadir platelet count and incidence of major bleeds. RESULTS: Among 2772 included infants, 224 (8%) developed a major bleed. Of the infants with a major bleed, 92% (206/224) had a nadir platelet count ≥50×109/L. The incidence of major bleeds was 8% among infants with and without severe thrombocytopenia (platelet count <50×109/L), 18/231 (95% CI 5 to 12) and 206/2541 (95% CI 7 to 9), respectively. Similarly, after adjustment for measured confounders, there was no notable association between nadir platelet counts below versus above 50×109/L and the occurrence of major bleeds (OR 1.09, 95% CI 0.61 to 1.94). CONCLUSION: In very preterm infants, the vast majority of major bleeds occur in infants without severe thrombocytopenia.

Brain MRI Injury Patterns across Gestational Age among Preterm Infants with Perinatal Asphyxia.

INTRODUCTION: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns. METHODS: Retrospective multicenter study included infants with gestational age (GA) 24.0­36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0­31.9 (group 2), and 32.0­36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0­44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18­24 months corrected age. RESULTS: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8-58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3-4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0-1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1-21.7) around TEA were associated with adverse neurodevelopmental outcomes. CONCLUSION: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes.