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We report our experience with transcatheter patent ductus arteriosus (PDA) closure in premature infants and compare patients grouped by the device used for closure: the Microvascular Plug, “MVP” (Medtronic, Minneapolis, MN); Micro Plug Set, “Micro Plug” (KA Medical, Minneapolis, MN); and Amplatzer Piccolo Occluder, “Piccolo” (Abbot, Santa Clara, CA). We also report trends in device selection over time. Studies examining outcomes according to device selection for PDA closure in premature infants are lacking. We performed a retrospective review of all percutaneous PDA closures in premature infants at a single center (June 2018–May 2021). Patients were grouped by initial device selected for PDA closure (intention to treat). Institutional Review Board approval was obtained. 58 premature infants [MVP (n = 25), Micro Plug (n = 25), and Piccolo (n = 8)] underwent successful transcatheter PDA closure (mean gestational age 27 weeks 2 days; mean weight at procedure 1.4 kg; mean age at procedure 28 days). Pre-procedural demographics, procedural data, and follow-up data were similar between groups. There were no significant procedural adverse events. Three devices (2 MVP, 0 Micro Plug, 1 Piccolo p = 0.27) embolized after the procedure. One other device was removed for concern for aortic obstruction. Device selection evolved with a clear trend toward the Micro Plug device over time. Demographic, procedural, and follow-up data were similar between the MVP, Micro Plug, and Piccolo groups. The Micro Plug did not require exchange for suboptimal fitting or embolize and became our preferred device in most cases.

Objective This study aimed to evaluate characteristics and outcomes in preterm infants with extubation failures in their first week of life. Study Design Retrospective chart review of infants born between 24 and 27 weeks' gestational age at the Sharp Mary Birch Hospital for Women and Newborns between January 2014 and December 2020 who had an extubation attempt within the first 7 days of life. Infants that were successfully extubated were compared with those who required reintubation in the first 7 days. Maternal and neonatal outcome measures were analyzed. Results A total of 215 extremely preterm infants had an extubation attempt in the first 7 days of life. Forty-six infants (21.4%) failed extubation and were reintubated within the first 7 days. Infants who failed extubation had a lower pH (p Conclusion In this cohort of extremely preterm infants that failed extubation in the first week of life, there were as increased risk of multiple morbidities. Base deficit, pH, and number of surfactant doses prior to first extubation may be useful tools in predicting which infants are likely to have early extubation success, but this needs prospective study. Key Points

Manganese (Mn) neurotoxicity is a concern in neonates receiving parenteral nutrition (PN). Prior studies have identified Mn contamination of PN ingredients as a source of daily Mn exposure from PN. This study was conducted to determine which neonatal PN ingredients are sources of this unintentional Mn delivery.Mn concentration was measured in different lot numbers of individual PN ingredients using inductively coupled plasma-mass spectrometry. PN admixtures were then prepared using standard doses of the tested individual ingredients, and admixture Mn concentration was measured.Magnesium sulfate and calcium gluconate are the major contributors to hidden unintentional Mn exposure in neonatal PN. Maximum measured Mn concentrations in these two ingredients were 443 and 46.8 mcg/L, respectively. Sodium phosphate and potassium phosphate were the next highest at 40 and 24 mcg/L, respectively. Other ingredients contained a trivial or no measurable quantity of Mn. PN admixture Mn content was 16%-30% higher than predicted values based on individual ingredient Mn content. If infused at 150 ml/kg/day, a standard neonatal PN admixture with no added Mn is capable of unintentionally delivering up to 0.9 mcg/kg/day Mn.Neonatal PN without any added Mn provides close to the American Society for Parenteral and Enteral Nutrition (ASPEN)-recommended Mn dosage of 1 mcg/kg/day. This supports the potential utility of a Mn-omission approach to trace element provision in neonatal PN. Further studies are needed to test such an approach and to evaluate the clinical significance of unintended Mn delivery in neonates receiving PN.

Clinicians favour low oxygen concentrations when resuscitating preterm infants immediately after birth despite inconclusive evidence to support this practice. Prospective meta-analysis (PMA) is a novel approach where studies are identified as eligible for inclusion in the meta-analysis before their results are known.To explore whether high (60%) or low (30%) oxygen is associated with greater efficacy and safety for the initial resuscitation (immediately after birth) of preterm infants born at29 weeks' gestation.We will conduct a prospective meta-analysis (PMA) with individual participant data (IPD). We will perform a systematic search to identify ongoing RCTs including infants29 weeks' gestation randomised to high (60%) or low (30%) oxygen for initial resuscitation after birth. IPD will be sought for all infants randomised for the purpose of meta-analysis. We will employ a one-stage random-effects approach to IPD meta-analysis. Potential heterogeneity and the differential effect of high or low oxygen will be explored through subgroup and interaction analyses. The primary outcome of this study is all-cause mortality prior to hospital discharge. There will be a follow-up analysis of neurodevelopmental outcomes once available.The results of neonatal outcomes at hospital discharge are expected by 2025, and neurodevelopmental outcomes by 2027.

The aim of this study is to investigate whether the purported benefits of delayed cord clamping (DCC) translate into a reduction in mortality and intraventricular hemorrhage (IVH) among preterm neonates in practice. This was a prospective cohort study of very preterm infants constructed from data from the California Perinatal Quality Care Collaborative for infants admitted into 130 California neonatal intensive care units (NICUs) within the first 28 days of life from 2016 through 2020. Individual-level analyses were conducted using log-binomial regression models controlling for confounders and allowing for correlation within hospitals to examine the relationship of DCC to the outcomes of mortality and IVH. Hospital-level analyses were conducted using Poisson regression models with robust variance controlling for confounders. Among 13,094 very preterm infants included (5,856 with DCC and 7,220 without), DCC was associated with a 43% lower risk of mortality (adjusted risk ratio [aRR]: 0.57; 95% confidence interval [CI]: 0.47-0.66). Furthermore, every 10% increase in the hospital rate of DCC among preterm infants was associated with a 4% lower hospital mortality rate among preterm infants (aRR: 0.96; 95% CI: 0.96-0.99). DCC was associated with severe IVH at the individual level, but not at the hospital level. At the individual level and hospital level, the use of DCC was associated with lower mortality among preterm infants admitted to NICUs in California. These findings are consistent with clinical trial results, suggesting that the effects of DCC seen in clinical trials are translating to improved survival in practice.· DCC was associated with lower mortality among very preterm newborns in California.. · Hospitals using DCC more often had lower very preterm mortality.. · DCC was not associated with IVH at the hospital level..

Adjuvant respiratory therapies in preterm neonates aim to reduce long-term morbidities and mortality. Commonly utilized therapies include caffeine, systemic glucocorticosteroids, inhaled steroids, inhaled bronchodilators, and diuretics. This review discusses the available literature that supports some of these practices and points out where clinical practices are not corroborated by evidence. Therapies with no proven clinical benefit must be weighed against potential adverse effects.

Cardiac point of care ultrasound (POCUS) is increasingly being utilized in neonatal intensive care units to provide information in real time to aid clinical decision making. While training programs and scope of practice have been well defined for other specialties, such as adult critical care and emergency medicine, there is a lack of structure for neonatal cardiac POCUS. A more comprehensive and advanced hemodynamic evaluation by a neonatologist has previously published its own clinical guidelines and specific rigorous training programs have been established to achieve competency in neonatal hemodynamics. However, it is becoming increasingly evident that access and training for basic cardiac assessment by ultrasound enhances bedside clinical care for specific indications. Recently, expert consensus POCUS guidelines for use in neonatal and pediatric intensive care endorsed by the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) have been published to guide the clinicians in using POCUS for specific indications, though the line between cardiac POCUS and advanced hemodynamic evaluation remains somewhat fluid.Conclusion: This article is focused on neonatal cardiac POCUS and its evolution, value, and limitations in the modern neonatal clinical practice. Cardiac POCUS can provide physiological and hemodynamic information in making clinical decisions while dealing with neonatal emergencies. However, it should be applied only for the specific indications and should be performed by a clinician trained in cardiac POCUS. There is an urgent need of developing cardiac POCUS curriculum and certification to support a widespread and safe use in neonates. What is Known: • International training guidelines and curriculum have been published for neonatologist-performed echocardiography (NPE) or targeted neonatal echocardiography (TNE). • International evidence-based guidelines for use of point of care ultrasound (POCUS) in neonates and children have been recently published. What is New: • Cardiac POCUS is increasingly being incorporated in neonatal practice for emergency situations. However, one must be aware of its specific indications and limitations, especially for the neonatal clinical practice. • Cardiac POCUS and NPE/TNE are continuum of cardiac imaging with different indications and training requirements.

There is a large body of evidence demonstrating that delaying clamping of the umbilical cord provides benefits for term and preterm infants. These benefits include reductions in mortality in preterm infants and improved developmental scores at 4 years of age in term infants. However, non-breathing or non-vigorous infants at birth are excluded due to the perceived need for immediate resuscitation. Recent studies have demonstrated early physiological benefits in both human and animal models if resuscitation is performed with an intact cord, but this is still an active area of research. Given the large number of ongoing and planned trials, we have brought together an international group that have been intimately involved in the development or use of resuscitation equipment designed to be used while the cord is still intact. In this review, we will present the benefits and limitations of devices that have been developed or are in use. Published trials or ongoing studies using their respective devices will also be reviewed.

Objective To assess the relationship between cerebral oxygenation in the first 72 h of life and neurodevelopmental impairment (NDI) at 2 years corrected age in former premature infants. Study design Prospective observational cohort study of 127 infants

Objective The aim of the study is to describe the rates of neonatal death and severe neonatal morbidity in a contemporary cohort, as well as to evaluate the predictive value of birth gestational age (GA) and birth weight, independently and combined, for neonatal mortality and morbidity in the same contemporary cohort. Study Design We performed a secondary analysis of an international, multicenter randomized controlled trial of delayed umbilical cord clamping versus umbilical cord milking in preterm infants born at 230/7 to 316/7 weeks of gestation. The current analysis was restricted to infants delivered Results Of 474 neonates in the original trial, 180 (38%) were included in this analysis. Overall, death occurred in 27 (15%) and severe morbidity in 139 (77%) neonates. Rates of mortality and morbidity declined with increasing GA (mortality 54% at 23 vs. 9% at 27 weeks). SGA infants (n = 25) had significantly higher mortality compared with non-SGA infants across all GAs (p Conclusion Death and severe neonatal morbidity declined with advancing GA, with higher rates of death in SGA infants. Birth GA and birth weight were both good predictors of outcomes; however, combining the two was not more predictive, even in SGA infants. Key Points

OBJECTIVE This study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences. STUDY DESIGN The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites' IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent. RESULTS Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, p

Iatrogenic manganese (Mn) neurotoxicity is a safety concern in neonates receiving parenteral nutrition (PN). Prior studies suggest Mn contamination of PN ingredients represents an unintended source of Mn delivery. In order to determine the relative contribution of unsourced Mn to total Mn exposure in neonatal PN, this study measured Mn concentrations in neonatal PN solutions using inductively coupled plasma mass spectrometry. Solutions prepared using a standard fixed dose neonatal multiple trace element product were compared with test solutions prepared using individual trace element ingredients not including Mn. The standard solutions (n = 6) contained a mean (SD) Mn concentration of 56.63 μg/L (0.94), compared with 6.04 μg/L (0.39) in the test solutions without added Mn (n = 6). This study suggests that neonatal PN contains significant quantities of Mn not intentionally added during PN preparation. Further studies are needed to identify individual ingredient sources of unintentional Mn, and the feasibility of Mn omission strategies.

Purpose Sudden expected deterioration is common in neonates. The established resuscitation guidelines provide excellent framework to stabilize these infants. However, physical examination in sick neonates is limited in identifying underlying pathology. The purpose of crashing infant protocol (CIP) is specifically to design an ultrasound guided adjunct approach for use in neonatal emergencies, and it can be applied in both term and pre-term neonates in any emergency clinical setting such as neonatal intensive care unit (NICU), post-natal ward, delivery room, emergency room or during transport. Methods An expert consensus was reached using a modified anonymous electronic Delphi strategy for the voting process. The statement guidelines have been prepared according to the international Appraisal of Guidelines, Research and Evaluation (AGREE). Results A total of 20 recommendations on the use of POCUS in the crashing infant were assessed. There was strong agreement from all panelists on 16 recommendations and agreement on 4 recommendations. Conclusions The newly proposed CIP and recommendations can be used as an adjunct to the current neonatal resuscitation guidelines. The CIP protocol is proposed based upon preidentified steps focused on gaining information regarding pathophysiology in infants with unexplained clinical deterioration or those not responding to the standard resuscitation.

To determine differences in the duration and level of resuscitation between infants that achieve a peripheral oxygen saturation (SpO2) of 80% by 5 min compared with those who remain below 80% saturation. Infants

The long-term effects of maternal diabetes on preterm infant neurodevelopment are unknown. This study aims to determine if there was an increased likelihood of neurodevelopmental impairment in preterm infants born to mothers with diabetes. A retrospective cohort study was conducted on preterm infants with neurodevelopmental evaluations at 18–36 months corrected age using the Bayley Scales of Infant and Toddler Development Third edition. 680 former preterm infants were evaluated. There was no difference in cognitive, language, and motor scores. Infants born to diabetic mothers with AMA were significantly different in cognitive (adjusted-β (a-β),−7.24 [95%CI, −11.719 to −2.769]; P = 0.002) and language domains (a-β,−7.783 [95%CI, −13.603 to −1.963]; (P = 0.009). There was no significant difference in neurodevelopmental outcomes of preterm infants exposed to maternal diabetes. Preterm infants born to mothers with diabetes and AMA demonstrated lower cognitive and language scores at 2 years corrected age.

Objective Delayed cord clamping (DCC) and 21 to 30% O2 resuscitation is recommended for preterm infants but is commonly associated with low pulmonary blood flow (Qp) and hypoxia. 100% O2 supplementation during DCC for 60 seconds followed by 30% O2 may increase Qp and oxygen saturation (SpO2). Study design Preterm lambs (125-127 days of gestation) were resuscitated with 100% O2 with immediate cord clamping (ICC, n = 7) or ICC + 30% O2, and titrated to target SpO2 (n = 7) or DCC + 100% O2 for 60 seconds, which followed by cord clamping and 30% O2 titration (n = 7). Seven preterm (23-27 weeks of gestation) human infants received continuous positive airway pressure (CPAP) + 100% O2 for 60 seconds during DCC, cord clamping, and 30% O2 supplementation after cord clamping. Results Preterm lambs in the ICC + 100% O2 group resulted in PaO2 (77 ± 25 mmHg), SpO2 (77 ± 11%), and Qp (27 ± 9 mL/kg/min) at 60 seconds. ICC + 30% O2 led to low Qp (14 ± 3 mL/kg/min), low SpO2 (43 ± 26%), and PaO2 (19 ± 7 mmHg). DCC + 100% O2 led to similar Qp (28 ± 6 mL/kg/min) as ICC + 100% O2 with lower PaO2. In human infants, DCC + CPAP with 100% O2 for 60 seconds, which followed by weaning to 30% resulted in SpO2 of 92 ± 11% with all infants >80% at 5 minutes with 100% survival without severe intraventricular hemorrhage. Conclusion DCC + 100% O2 for 60 seconds increased Qp probably due to transient alveolar hyperoxia with systemic normoxia due to "dilution" by umbilical venous return. Larger translational and clinical studies are warranted to confirm these findings. Key points · Transient alveolar hyperoxia during delayed cord clamping can enhance pulmonary vasodilation.. · Placental transfusion buffers systemic oxygen tension and limits hyperoxia.. · Use of 100% oxygen for 60 seconds during DCC was associated with SpO2 ≥80% by 5 minutes..

Recently been updated, neonatal resuscitation guidelines1 continue to recommend (level 2A) delayed cord clamping (DCC) in preterm newborns not requiring resuscitation at birth. Since the publication of the last guidelines2 the level of evidence has strengthened from limited data on efficacy and safety to moderate quality of evidence from randomized trials and their meta-analysis.3 Preterm infants receiving DCC were less likely to receive red blood cell transfusion and … E-mail: stefano.ghirardello{at}mangiagalli.it

It is recommended to delay cord clamping in healthy term infants for at least 60- and 180-s in high- and limited-resource environments, as delayed cord clamping lowers the incidence of anemia and iron deficiency and improves neurodevelopment. There are improvements in hemodynamic parameters such as peripheral arterial oxygen saturation, heart rate, cardiac output, and cerebral oxygenation. Historically, delayed cord clamping caused a higher rate of hyperbilirubinemia and phototherapy, but more recent evidence suggests this may no longer be the case. In limited-resource environments delayed cord clamping may reduce anemia and iron deficiency potentially improving neurodevelopmental outcomes. The use of delayed cord clamping in newborn infants with intrauterine growth restriction or monochorionic twins is limited and further evidence is needed before it can be formally recommended.

Studies aimed at reducing neonatal anaemia or transfusing higher blood volumes did not find improvement in neurodevelopmental function at two years of age. This study investigated the relationship between the receipt, timing, and number of red blood cell (RBC) transfusions and neurodevelopmental outcomes among preterm infants.This is a retrospective review of preterm infants (gestational age34 weeks) with a full neurodevelopmental assessment at 18-36 months corrected age from October 2008 to September 2020. Bayley Scales of Infant and Toddler Development, third edition and the Modified Checklist for Autism in Toddlers were collected. Multivariable regressions were used to evaluate neurodevelopmental outcomes.654 preterm infants were evaluated with a mean follow-up of 25 months. 295 infants (45%) received a total of 1,322 blood transfusions. After adjustment for gestational age, baseline morbidity, and socioeconomic status, receipt of RBC transfusion was associated with decreased two-year cognitive and motor function, but not language (p=0.047, 0.025, and 0.879, respectively). There was no significant difference in outcomes between receipt of transfusion in the first week of life compared to after. Number of transfusions was associated with decreased cognitive, language, and motor function (all p0.001), and increased likelihood to develop severe neurodevelopmental impairment (adjusted-odds ratio, 1.09; 95% confidence interval, 1.03-1.15; p=0.004).Our study demonstrates an association between RBC transfusion and lower cognitive and motor outcomes at two-years after adjustment for prematurity and illness at birth. Increasing number of transfusions worsened neurodevelopmental outcomes.

Introduction Respiratory distress syndrome (RDS) or surfactant deficiency occurs primarily in premature infants resulting in composite outcomes of death or bronchopulmonary dysplasia. Initial management strategies for preterm infants with RDS includes early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen (FiO2), and may include the use of less invasive surfactant administration (LISA) to avoid the need for mechanical ventilation. In order to optimise success of non-invasive support, the use of early caffeine therapy may be critical to the success of LISA. The objective of our trial is to evaluate whether infants that receive early caffeine, CPAP and surfactant via the LISA method compared with infants that receive caffeine and CPAP alone, have a decreased need for invasive mechanical ventilation in the first 72 hours of life. Methods and analysis CaLI is an unblinded multicentre, randomised controlled, trial of 180 preterm infants (24+0–29+6 weeks corrected GA). Criteria for intubation/treatment failure will follow guidelines for the management of RDS, including: (1) CPAP level of 6–8 cmH20 and FiO2>0.40 required to maintain saturations 90%–95% for 2 hours after randomisation; (2) a pH of 7.15 or less or a paCO2>65 mm Hg on any (2) blood gases (arterial/capillary/or venous) at least 2 hours after randomisation and in the first 72 hours of life; (3) continued apnoea/bradycardia/desaturation events despite nasal intermittent minute ventilation mode of ventilation. Infants will be randomised by 1 hour of life and caffeine/LISA treatments administered by 2 hour of life. Caffeine will be administered prior to surfactant in the LISA arm and before 2 hours of life in the control arm. Ethics and dissemination Chiesi Farmaceutici, S.p.A is the sponsor of CaLI. Ethical approval has been obtained. Results will be submitted for publication in peer reviewed journals. Trial registration number www.Clinicaltrials.gov:NCT04209946; Pre-results.

Jimenez and colleagues (BJOG 2020 xxxx) present outcomes from 403 SARS-CoV-2 positive pregnant women and their newborns that received either delayed cord clamping > 30 seconds (DCC) or early cord clamping < 30 seconds (ECC). The recommendations from the Spanish Ministry of health and the International Federation of Gynecology and Obstetrics (FIGO) discouraged the use of DCC in efforts to reduce the potential for vertical transmission of SARS-CoV-2 (Poon LC, et al. Int J Gynecol Obstet 2020, 149, 273-286). Jimenez and colleagues demonstrated that there was no increased transmission with DCC. Overall, the transmission rates were low. Infants who had DCC also had higher rates of breastfeeding and early skin to skin.

BACKGROUND:Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant.METHODS:A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers’ discretion.RESULTS:Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different.CONCLUSIONS:In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

The first case of novel coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported in November2019. The rapid progression to a global pandemic of COVID-19 has had profound medical, social, and economic consequences. Pregnant women and newborns represent a vulnerable population. However, the precise impact of this novel virus on the fetus and neonate remains uncertain. Appropriate protection of health care workers and newly born infants during and after delivery by a COVID-19 mother is essential. There is some disagreement among expert organizations on an optimal approach based on resource availability, surge volume, and potential risk of transmission. The manuscript outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother, including three optional variations of current standards involving shared-decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and postdischarge care. The availability of resources may also drive the application of these guidelines. More evidence and research are needed to assess the risk of vertical and horizontal transmission of SARS-CoV-2 and its impact on fetal and neonatal outcomes. KEY POINTS: · The risk of vertical transmission is unclear; transmission from family members/providers to neonates is possible.. · Optimal personal-protective-equipment (airborne vs. droplet/contact precautions) for providers is crucial to prevent transmission.. · Parents should be engaged in shared decision-making with options for rooming in, skin-to-skin contact, and breastfeeding..

Current guidelines support the use of a cardiac monitor during neonatal resuscitation. Preterm infants randomized to a novel ECG algorithm displayed a heart rate sooner than the conventional ECG algorithm. Although resuscitation outcomes were not different, availability of an earlier heart rate may benefit neonatal providers during high-risk resuscitations.

In the past five years, umbilical cord management in both term and preterm infants has come full circle, going from the vast majority of infants receiving immediate cord clamping to virtually all governing organizations promoting placental transfusion, mainly in the form of delayed cord clamping (DCC). Placental transfusion refers to the transfer of more blood components to the infant during the first few minutes after birth. The different strategies for ensuring placental transfusion to the baby include delayed (deferred) cord clamping, milking of the attached cord before clamping, and milking of the cut cord. In this review, we address the current evidence to date for providing placental transfusion in different circumstances and the methods for implementation. We also highlight the gaps in knowledge and areas for future research.

BACKGROUND: Permissive hypercapnia is a lung-protection strategy. We sought to review our current clinical practice for the range of permissive hypercapnia and identify the relationship between PaCO2 and pH and adverse outcomes. METHODS: A secondary analysis of a delayed cord-clamping clinical trial was performed on all arterial blood gas tests in the first 72 h in infants RESULTS: 147 infants with birthweight of 1,206 ± 395 g and gestational age of 28 ± 2 weeks were included. Of the 1,316 total samples, CONCLUSION: The routine targeting of higher than normal PaCO2 goals may lead to a low incidence of hypocapnia and associated adverse events. Hypercapnia is common, and moderate hypercapnia may increase the risk of neurologic injury and provide little pulmonary benefit.

OBJECTIVE: To compare the effect of umbilical cord milking vs delayed cord clamping (DCC) on neurodevelopmental and health outcomes in very preterm infants at 22–26 months of corrected age. STUDY DESIGN: Neurodevelopmental outcomes at 2 years of age were assessed using the Bayley Scales of Infant Development, third edition, and a standardized neurologic examination. Data regarding pulmonary morbidities, neurosensory impairments, and hospitalizations were obtained by parental interview. Intention-to-treat was used for primary analyses. RESULTS: Of the 197 infants enrolled in the original study there were 15 deaths, 5 in the umbilical cord milking group and 10 in DCC group. Of the remaining infants, 135 (74%) were assessed at 22–26 months of corrected age. Demographics in umbilical cord milking (n = 70) and DCC (n = 65) groups were similar. Infants randomized to umbilical cord milking at birth had significantly higher cognitive and language composite scores, and were less likely to have a cognitive composite score of

To determine if umbilical cord milking is detrimental in compromised term/near-term infants. A retrospective analysis of infants with abnormal cord gases (cord arterial or venous pH of ≤ 7.1 or base deficit > −12). We collected maternal risk factors, cord management, birth, and neonatal outcomes during hospitalization. We found 157 infants who met the criteria for abnormal cord gases. Thirty-six of those had umbilical cord milking at delivery. There was no significant difference in neonatal outcomes, but fewer infants in the cord milking group needed resuscitation (38 vs. 56%, p = 0.07) and ongoing respiratory support (19 vs. 31%, p = 0.16) compared to the immediate clamping group. While not significant, infants who received cord milking at birth needed less resuscitation and ongoing respiratory support. This study suggests that umbilical cord milking appears to be a safe therapy when acidosis is present and when resuscitation is needed.

The current recommendation for umbilical cord management of non-vigorous infants (limp, pale, and not breathing) who need resuscitation at birth is to immediately clamp the umbilical cord. This recommendation is due in part to insufficient evidence for delayed cord clamping (DCC) or umbilical cord milking (UCM). These methods may provide a neuroprotective mechanism that also facilitates cardiovascular transition for non-vigorous infants at birth.

Informed consent is a process ensuring that subjects enrolled in research are appropriately informed of the risks and benefits. While this process is well-defined when it is possible and practical to obtain consent prior to the research intervention, it can be less clear in cases of deferred or waived consent. Defining minimal risk, such as when research is attempting to determine which of two currently practiced interventions is safest and/or most effective, is critical to moving forward in establishing appropriate care in newborns. For perinatal/neonatal research the challenge lies between the ethical justification for approaching women in labor or under medication vs. the scientific integrity of excluding a number of subjects that may potentially benefit the most from an intervention. Researchers must work with their IRBs as well as families who have participated in trials to determine the most appropriate method for obtaining informed consent from expectant parents. Clinical researchers and IRBs ultimately need to find a middle ground for the appropriate use of deferred or waived consent.

ObjectiveTo evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants

In comparing placental transfusion strategies, blood obtained from an umbilical cord that has been "milked" vs one in which clamping was simply delayed contains mesenchymal stromal cells in addition to solely hematopoietic stem cells, a composition more favorable for hematopoiesis, as suggested by its superior rescue of lethally irradiated bone marrow-depleted mice.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required

The optimal timing of clamping and cutting the umbilical cord at birth among infants with congenital heart disease (CHD) remains a subject of controversy and debate. The benefits of delayed umbilical cord clamping (DCC) among term infants without CHD are well described, but the evidence base for DCC among infants with CHD has not been characterized adequately. The goals of the present review are to: 1) compare outcomes of DCC versus early cord clamping (ECC) in term (≥37 weeks of gestation) infants; 2) discuss potential risk/benefit profiles in applying DCC among term infants with CHD; 3) use rigorous systematic review methodology to assess the quality and quantity of published reports on cord clamping practices among term infants with CHD; 4) identify needs and opportunities for future research and interdisciplinary collaboration. Our systematic review shows that previous trials have largely excluded infants with CHD. Therefore, the supposition that DCC is advantageous because it is associated with improved neurologic and hematologic outcome is untested in the CHD population. Given that CHD is markedly heterogeneous, to minimize unnecessary and potentially harmful cord clamping practices, identification of subgroups (single-ventricle, cyanotic lesions) most likely to benefit from optimal cord clamping practices is necessary to optimize risk/benefit profiles. The available evidence base suggests that contemporary, pragmatic, randomized controlled trials comparing DCC with ECC among infants with CHD are needed.

Objective To evaluate changes in cerebral oxygenation, peripheral arterial oxygenation, respiratory status, and administered fraction of inspired oxygen during the first 10 minutes of life in premature infants receiving umbilical cord milking compared with delayed cord clamping (DCC). Study design Premature infants born at 230/7 to 276/7 weeks of gestation were randomized to umbilical cord milking or DCC. A near infrared spectroscopy sensor, pulse oximeter, and electrocardiogram electrodes were placed. Pulse rate, cerebral tissue oxygenation, peripheral oxygen saturation, airway pressure, and fraction of inspired oxygen were collected for 10 minutes in the delivery room. Longitudinal models were used to compare effects of umbilical cord milking and DCC. Results Fifty-six infants had cerebral oximetry and advanced monitoring at birth. There was an increased incidence of severe intraventricular hemorrhage in infants who received umbilical cord milking compared with DCC (P = .0211). Longitudinal models suggested that peripheral oxygen saturation was higher in the umbilical cord milking group in the first 4 minutes (P = .0221) and that mean airway pressures were lower in the umbilical cord milking group after the first 7 minutes (P = .0072). No statistical differences were observed for fraction of inspired oxygen, cerebral tissue oxygenation, or heart rates. Conclusions The data suggest that the rapid transfer of blood during umbilical cord milking may facilitate lung expansion with improved pulmonary blood flow, but may also increase cerebral blood flow, resulting in severe intraventricular hemorrhage. Trial Registration ClinicalTrials.gov : NCT03145142

ObjectiveTo compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given.Study designA total of 202 neonates of