Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Twin Premature Infants With Riboflavin and Biotin Deficiency Presenting With Refractory Lactic Acidosis, Rash, and Multiorgan Failure During Prolonged Parenteral Nutrition.

We are reporting monochorionic, diamniotic twin premature infants born at 25 weeks and 6 days gestation with riboflavin (vitamin B2) and biotin (vitamin B7) deficiency, while on prolonged total parenteral nutrition (TPN) during vitamin shortage. They presented initially with skin rash, lactic acidosis, and thrombocytopenia. Both twins progressed to severe respiratory failure, severe lactic acidosis, with refractory vasodilatory shock, pancytopenia, ischemic bowel injury, acute kidney injury, liver injury, and capillary leak syndrome leading to death of twin A. The surviving twin B was diagnosed with riboflavin and biotin deficiency that presented with abnormal metabolic work up suggestive of maple syrup urine disease, glutaric acidemia type 2, and X-linked adrenoleukodystrophy. Twin B was started on riboflavin and biotin supplementation at 41 days of life, with rapid improvement in clinical findings and laboratory abnormalities within days of starting biotin and riboflavin supplementation. He was discharged home in stable condition at 49 weeks of postmenstrual age.

Extremely Preterm Infant Born to a Mother With Severe COVID-19 Pneumonia.

Little is known about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnant women, fetuses, and neonates, especially when the virus is contracted early in pregnancy. The literature is especially lacking on the effects of SARS-CoV-2 on extremely preterm (<28 weeks gestation) infants who have underdeveloped immune systems. We report the case of an extremely preterm, 25-week 5-days old infant, born to a mother with severe COVID-19 (coronavirus disease-2019) pneumonia. In this case, there is no evidence of vertical transmission of SARS-CoV-2 based on reverse transcription-polymerase chain reaction testing, despite extreme prematurity. However, it appears that severe maternal COVID-19 may have been associated with extremely preterm delivery, based on observed histologic chorioamnionitis. This is the first reported case of an extremely preterm infant born to a mother with severe COVID-19 pneumonia who required intubation, and was treated with hydroxychloroquine, azithromycin, remdesivir, tocilizumab, convalescent plasma, inhaled nitric oxide, and prone positioning for severe hypoxemic respiratory failure prior to and after delivery of this infant. The infant remains critically ill with severe respiratory failure on high-frequency ventilation, inotropic support, hydrocortisone for pressor-resistant hypotension, and inhaled nitric oxide for severe persistent pulmonary hypertension with a right to left shunt across the patent ductus arteriosus and foramen ovale. Pregnant women or women planning to get pregnant should take all precautions to minimize exposure to SARS-CoV-2 to decrease adverse perinatal outcomes.

Multidrug Therapy for Refractory Immune Thrombocytopenia in Pregnancy.

BACKGROUND: Severe immune thrombocytopenia complicating pregnancy may require treatment beyond first-line medications (intravenous immunoglobulins or corticosteroids), but there is a paucity of literature on the use of such second-line agents in pregnancy. CASE: The patient is a 29-year-old woman with early-onset severe immune thrombocytopenia at 13 weeks of gestation. Maternal platelet counts reached a nadir of less than 5×10/L. The thrombocytopenia persisted despite first-line medications. Romiplostim, rituximab, and azathioprine were added to the therapeutic regimen. Platelet counts eventually stabilized at greater than 150×10/L before delivery. After delivery at term, the neonate had transient B-cell suppression, which was presumed to be secondary to rituximab, but was otherwise doing well and meeting all milestones at 7 months of age. CONCLUSION: The addition of second-line agents was associated with sustained elevation in maternal platelet counts and may have obviated the need for splenectomy.

Necrotizing Enterocolitis: Enhancing Awareness for the General Practitioner.

Necrotizing enterocolitis (NEC) has been recognized for well over 5 decades yet remains the most common life-threatening surgical emergency in the newborn. The incidence of NEC has decreased steadily in preterm and very-low-birthweight infants over several decades and is typically uncommon in term newborns and infants with a birthweight greater than 2,500 g. Evidence accumulating during the past decade, however, suggests that practitioners should consider NEC in this broader subset of term infants with chromosomal and congenital anomalies complicated by heart or gastrointestinal defects when signs and symptoms of feeding intolerance, abdominal illness, or sepsis are present. The short- and long-term consequences of NEC are devastating in all infants, and although early disease recognition and treatment are essential, promoting human milk feeding as a primary modality in prevention is critical. This article highlights our current understanding of the pathophysiology, the clinical presentation, the risk factors for NEC in term infants compared with premature infants, and the treatment of NEC and discusses strategies in the prevention of NEC. Finally, we review the long-term consequences of NEC and the importance of primary care practitioners in the long-term care of infants after hospitalization for NEC.

Decrease in delivery room intubation rates after use of nasal intermittent positive pressure ventilation in the delivery room for resuscitation of very low birth weight infants.

BACKGROUND: The literature supports minimizing duration of invasive ventilation to decrease lung injury in premature infants. Neonatal Resuscitation Program recommended use of non-invasive ventilation (NIV) in delivery room for infants requiring prolonged respiratory support. OBJECTIVE: To evaluate the impact of implementation of non-invasive ventilation (NIV) using nasal intermittent positive pressure ventilation (NIPPV) for resuscitation in very low birth infants. STUDY DESIGN: Retrospective study was performed after NIPPV was introduced in the delivery room and compared with infants receiving face mask to provide positive pressure ventilation for resuscitation of very low birth weight infants prior to its use. Data collected from 119 infants resuscitated using NIPPV and 102 infants resuscitated with a face mask in a single institution. The primary outcome was the need for endotracheal intubation in the delivery room. Data was analyzed using IBM SPSS Statistics software version 24. RESULTS: A total of 31% of infants were intubated in the delivery room in the NIPPV group compared to 85% in the Face mask group (p=<0.001). Chest compression rates were 11% in the NIPPV group and 31% in the Face mask group (p<0.001). Epinephrine administration was also lower in NIPPV group (2% vs. 8%; P=0.03). Only 38% infants remained intubated at 24hours of age in the NIPPV group compared to 66% in the Face mask group (p<0.001). Median duration of invasive ventilation in the NIPPV group was shorter (2days) compared to the Face mask group (11days) (p=0.01). The incidence of air-leaks was not significant between the two groups. CONCLUSION: NIPPV was safely and effectively used in the delivery room settings to provide respiratory support for VLBW infants with less need for intubation, chest compressions, epinephrine administration and subsequent invasive ventilation.

Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future.

Respiratory distress syndrome (RDS) due to surfactant deficiency is the most common cause of respiratory failure in preterm infants. Tremendous progress has been made since the original description that surfactant deficiency is the major cause of RDS. Surfactant therapy has been extensively studied in preterm infants and has been shown to significantly decrease air leaks and neonatal and infant mortality. Synthetic and animal-derived surfactants from bovine as well as porcine origin have been evaluated in randomized controlled trials. Animal-derived surfactants generally result in faster weaning of respiratory support, shorter duration of invasive ventilation, and decreased mortality when compared to first- or second-generation of synthetic surfactants, but some of the second-generation synthetic surfactants are at least not inferior to the animal-derived surfactants. Using a higher initial dose of porcine derived surfactant may provide better outcomes when compared with using lower doses of bovine surfactants, likely, due to compositional difference and/or the dose. Third-generation synthetic surfactant containing peptide analogs of surfactant protein B and C are currently being studied. Less invasive intra-tracheal surfactant administration techniques in spontaneously breathing neonate receiving noninvasive ventilator support are also being evaluated. In the present era, prophylactic surfactant is not recommended as it may increase the risk of lung injury or death. In the future, surfactants may be used as vector to deliver steroids, or used in combination with molecules, such as, recombinant Club Cell Protein-10 (rhCC-10) to improve pulmonary outcomes. Also, noninvasive surfactant administration techniques, such as aerosolization or atomization of surfactant may play a greater role in the future.

Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants.

OBJECTIVE: To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection. STUDY DESIGN: We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses. RESULTS: Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period. CONCLUSION: We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633.

Graded oxygen saturation targets and retinopathy of prematurity in extremely preterm infants.

BACKGROUND: We compared the incidence of severe retinopathy of prematurity (ROP) and need for laser treatment before and after implementing graded pulse oximeter oxygen saturation (SpO2) targets in extremely preterm infants. Mortality and other secondary outcomes were compared. METHODS: Before 2002, we used 90-94% as the SpO2 target in infants 24(0/7)-27(6/7)wk gestation and birth weight <1,000 g until 35(6/7) wk postmenstrual age (PMA). We implemented graded SpO2 targets based on vaso-obliterative and vaso-proliferative phases of ROP in 2002. Group 1 (1995-2001) before, and Group 2 (2003-2010) after implementation of graded SpO2 targets based on PMA (83-89% until 32(6/7) wk, 90-94% until 35(6/7) wk and >94% at ≥ 36 wk PMA). RESULTS: There were 267 patients in Group 1 and 220 in Group 2. There was no significant difference in birth weight or gestational age. Severe ROP (adjusted OR: 0.18, 95% CI: 0.11, 0.30; P < 0.001) and laser surgery rates (adjusted OR: 0.31, 95% CI: 0.18, 0.52; P < 0.001) decreased significantly in Group 2. There was no difference in mortality (adjusted OR: 0.74, 95% CI: 0.37, 1.49; P = 0.40). CONCLUSION: In this retrospective cohort study, implementation of graded SpO2 targets decreased severe ROP and need for laser therapy, without increasing mortality.