Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death.  Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Changes in middle cerebral artery velocimetry of fetuses diagnosed postnatally with mild or moderate hemolytic disease.

OBJECTIVES: To determine the longitudinal trends of middle cerebral artery peak systolic velocity (MCA PSV) in fetuses with mild or moderate hemolytic disease according to the need for postnatal therapy. DESIGN: Prospective cohort study. SETTING: University referral center. SAMPLE: Twenty-three fetuses from singleton alloimmunized pregnancies. METHODS: Serial measurements of MCA PSV were performed. After delivery, newborns were grouped by the need for postnatal management into mild hemolytic disease, which required no or only phototherapy (n = 14, group 1), and moderate hemolytic disease, where postnatal top-up or exchange transfusions were required (n = 9, group 2). MAIN OUTCOME MEASURES: Serial Doppler MCA PSV data transformed to multiples of the median, analyzed with linear regression and exponential models. RESULTS: We performed 83 measurements in group 1: 3-8 per fetus; mean GA at inclusion, 23 weeks and 65 measurements in group 2: 4-15 per fetus; mean GA at inclusion, 22 weeks. The estimated mean slopes of the MCA PSVs increased with the degree of postnatal therapy required (group 1: MCA PSV = 0.003 GA + 1.298; group 2: MCA PSV = 0.035 GA + 0.436). The relative average increments (RAI) were 4.7% and 7.1%, respectively. The two groups exhibited significant differences in mean slope and RAI (p<0.05). CONCLUSIONS: Fetuses that required postnatal transfusions due to hemolytic disease showed an enhanced progressive increase in MCA PSVs compared to those without transfusion requirement. This information might enable their identification during pregnancy.

Risk factors for tumors or leukemia development in the first two years of life.

OBJECTIVES: The objective of this study was to determine the incidence of neoplastic diseases and associated risk factors in the early stages of life. METHODS: Data were retrospectively assessed in 730,000 live births between 2000 and 2019. The occurrence of tumors was monitored in the neonatal, infant (1-12 months), and toddler (13-24 months) periods. Risk factors were divided into demographic, internal, and environmental factors. The control group consisted of subjects in the same age category without oncological diseases. RESULTS: A total of 452 neoplastic diseases were diagnosed in the study sample. In total, 24% (110/452) manifested during the neonatal period, 45% (203/452) in infants, and 31% (139/452) at the age of 13-24 months. Any genetic disease (OR 26.68; 95% CI 7.64-93.12) and medications used by the mother (OR 3.07; 95% CI 1.32-7.15) were identified as risk factors. Without adjustment for all factors, asphyxia in the first minute, a younger age of the mother, lower pregnancy, and the presence of a congenital defect manifested themselves as risk factors. CONCLUSIONS: The highest risk factors for the development of early childhood tumors were identified as with medications used by the mother before or during pregnancy and genetic diseases.

Measuring respiratory and heart rate using a fiber optic interferometer: A pilot study in a neonate model.

Introduction: The study aim was to test the safety and efficacy of a pad with optic fibers developed for monitoring newborn respiratory rate (RR) and heart rate (HR). Methods: Thirty New Zealand White rabbits were included, divided by weight into three groups. RR and HR were measured using two methods for each rabbit: ECG electrodes as the reference method and a newly developed pad with an experimental fiber optic system (EFOS) as the experimental method. Results: Analysis was performed on data for 29 rabbits (10 female, 34%; 19 male, 66%). EFOS performed better at measuring RR compared with HR. RR values did not differ significantly between the methods for the whole group (p = 0.151) or within each sex (female: p > 0.999; male: p = 0.075). Values for HR, however, did differ between methods for the whole group of animals (p < 0.001) and also within groups by sex (female: p < 0.001; male: p = 0.006). Conclusion: The results of this preclinical study demonstrate the potential of this non-invasive method using a fiber optic pad to measure HR and RR.

Hypotension in Preterm Infants (HIP) randomised trial.

OBJECTIVE: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation. DESIGN: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment. SETTING: 10 sites across Europe and Canada. PARTICIPANTS: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage. INTERVENTION: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management). PRIMARY OUTCOME: Survival to 36 weeks of PMA without severe brain injury. RESULTS: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038). CONCLUSION: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area. TRIAL REGISTRATION NUMBER: NCT01482559, EudraCT 2010-023988-17.

A rare form of ankyloblepharon filiforme adnatum associated with the Hay-Wells syndrome and a c.1709T>C mutation on the TP63 gene.

INTRODUCTION: Ankyloblepharon filiforme adnatum associated with Hay-Wells syndrome is a rare congenital disease caused by mutations in TP63 gene on the 3q27 chromosome. Here, we report a case of a new-born suffering from this syndrome in whom we detected a mutation c.1709T>C not previously included in the Ensemble database. CASE DESCRIPTION: A girl delivered in the 34th week of gestation from a physiological pregnancy was born with extensive burn-like skin defects, ankyloblepharon filiforme adnatum, palate cleft, onychodystrophy of all limbs and syndactyly of toes. Hay-Wells syndrome was suspected and confirmed by genetic examination. A heterozygous missense change c.1709T>C was found in the TP63 gene. This variant leads to a 570th codon exchange of leucine for proline (p.Leu570Pro) on the protein level. The eyelid separation was performed surgically, burns were treated locally and cosmetic surgeries correcting other defects are planned for the near future. The girl is still monitored by a multidisciplinary team. CONCLUSIONS: The mutation was not previously described in the literature or databases and should be included into these as probably pathogenic. A multidisciplinary approach is necessary to care for a patient with Hay-Wells syndrome, such care however can provide good results.