Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial.

BACKGROUND: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. METHODS: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial.

BACKGROUND: International guidelines recommend delayed umbilical cord clamping (DCC) up to 1 min in preterm infants, unless the condition of the infant requires immediate resuscitation. However, clamping the cord prior to lung aeration may severely limit circulatory adaptation resulting in a reduction in cardiac output and hypoxia. Delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) allows for an adequately established pulmonary circulation and results in a more stable circulatory transition. The decline in cardiac output following time-based delayed cord clamping (TBCC) may thus be avoided. We hypothesise that PBCC, compared to TBCC, results in a more stable transition in very preterm infants, leading to improved clinical outcomes. The primary objective is to compare the effect of PBCC on intact survival with TBCC. METHODS: The Aeriation, Breathing, Clamping 3 (ABC3) trial is a multicentre randomised controlled clinical trial. In the interventional PBCC group, the umbilical cord is clamped after the infant is stabilised, defined as reaching heart rate > 100 bpm and SpO2 > 85% while using supplemental oxygen < 40%. In the control TBCC group, cord clamping is time based at 30-60 s. The primary outcome is survival without major cerebral and/or intestinal injury. Preterm infants born before 30 weeks of gestation are included after prenatal parental informed consent. The required sample size is 660 infants. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management in very preterm infants at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. First registered on January 17, 2019.

Management of severe neonatal respiratory distress due to vertical transmission of severe acute respiratory syndrome coronavirus 2: a case report.

BACKGROUND: Neonates with severe acute respiratory syndrome coronavirus 2 infection are usually asymptomatic or have mild to moderate symptoms. Acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus 2 with respiratory insufficiency is rare. Therefore, information about the best intensive care strategy for neonates requiring mechanical ventilation is lacking. We report a neonatal case of severe acute respiratory distress syndrome, probably due to vertical transmission of severe acute respiratory syndrome coronavirus 2, complicated by Staphylococcus aureus sepsis. We aim to inform pediatric providers on the clinical course and acute management considerations in coronavirus disease-related neonatal acute respiratory distress syndrome. CASE PRESENTATION: A late preterm (gestational age 36 0/7 weeks) Caucasian girl was born from a severe acute respiratory syndrome coronavirus 2-positive mother and tested positive for severe acute respiratory syndrome coronavirus 2 at 19 hours after birth. She developed acute respiratory distress syndrome requiring intensive care admission and mechanical ventilation. The clinical course was complicated by S. aureus pneumonia and bacteremia. Multimodal management included well-established interventions for respiratory distress syndrome such as surfactant therapy, high-frequency oscillatory ventilation, and inhaled nitric oxide, combined with therapies extrapolated from adult care for severe acute respiratory syndrome coronavirus 2 patients such as dexamethasone, coronavirus disease 2019-specific immunoglobins, and prophylactic low-molecular-weight heparin. The neonate was successfully weaned from the ventilator and improved clinically. CONCLUSION: This case shows a rare but serious neonatal severe acute respiratory syndrome coronavirus 2 infection, leading to severe acute respiratory distress syndrome. Because of limited therapy guidelines for neonates, we suggest multimodal management with awareness of the possibility of S. aureus coinfection, to treat this age group successful.

Evaluation of bone mineralization in former preterm born children: Phalangeal quantitative ultrasound cannot replace dual-energy X-ray absorptiometry.

BACKGROUND: Preterm infants are at risk of impaired bone health in later life. Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative technique that is inexpensive, easy to use and radiation-free. The aim of this study was to investigate whether both techniques reveal equivalent results. MATERIALS AND METHODS: Sixty former preterm infants (31 boys; 29 girls) received a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS measured the amplitude dependent speed of sound (AD-SoS) and bone transit time (BTT) at metacarpals II-IV providing continuous values and Z-scores based on age and sex. Four statistical methods evaluated the association between both techniques: Pearson's correlation coefficients, partial correlation coefficients adjusted for gestational age, height and BMI, Bland-Altman analysis and cross tabulation. RESULTS: Both techniques showed a statistically significant weak correlation for continuous values as well as Z-scores (0.291-0.462, p < 0.05). Boys had significant and relatively high correlations (0.468-0.585, p < 0.05). In comparison, the correlations for girls were not significant. Correlation coefficients further decreased while calculating the partial correlations. The Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and specificity from 16% to 68%. Positive and negative predictive values ranged from 4% to 38% and 82% to 97%, respectively. CONCLUSIONS: We found statistically significant weak correlations and poor agreement between DXA and pQUS measurements. DXA is not equivalent to pQUS and therefore not replaceable by this technique in former preterm born children at the age of 9 to 10 years.

Fatal Complications after Pediatric Surgical Interventions: Lessons Learned.

Placement of catheters, drains, shunts, and tubes in children can lead to serious or even fatal complications at the moment of placement, such as hemorrhage at insertion, or in the longterm, such as infections and migration into adjacent organs. The clinician should always be aware of these potential complications, especially if the child is unwell. For postmortem diagnostic evaluation, either with a computed tomography scan or an invasive autopsy, all tubes, drains, shunts, and/or catheters should be left in situ. We present three cases with fatal complications after the placement of a chest drain, ventriculoperitoneal shunt, and gastrostomy tube.

[Infantile myofibroma: a neonate with a swelling on the arm]. / Het infantiel myofibroom: een neonaat met een gezwel van de onderarm.

BACKGROUND: An infantile myofibroma (IM) is a benign congenital soft-tissue tumour. IM is found in 1 per 150,000 live births, making it the most common fibrous tumour of infancy and early childhood. CASE DESCRIPTION: We report on a full-term neonate presenting with an irregular tumour mass on the right lower-arm. The mass measured 5 cm in diameter, with surface ulceration. Magnetic resonance imaging (MRI) revealed characteristics that could be consistent with malignancy. On the basis of a biopsy and subsequent polymerase chain reaction we were able to make a diagnosis of 'benign infantile myofibroma'. We chose for conservative treatment in the expectation that the tumour would regress spontaneously. CONCLUSION: Infantile myofibroma should be considered when a newborn presents with an atypical mass. It is difficult to make a diagnosis on the basis of the clinical characteristics alone due to the heterogeneous presentation. A definitive diagnosis can only be made following histological investigation.

Salpingitis. A rare cause of acute abdomen in a sexually inactive girl: a case report.

Salpingitis is an acute inflammation of the fallopian tubes, most commonly caused by sexually transmitted micro-organisms in adolescent and adult women. It is rarely found in sexually inactive girls and generally the result of a blood-borne or genitourinary infection. In young girls without a history of consensual sexual contact, the possibility of sexual abuse should be considered.Salpingitis usually presents as an acute abdomen. Appendicitis presents with almost the same symptoms as salpingitis. The diagnosis of salpingitis is often delayed until the presumed appendicitis is surgically explored.We describe an 11-year-old girl with salpingitis caused by Streptococcus pneumoniae.