Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Delayed cord clamping in healthy term infants: More harm or good?

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.

Umbilical Cord Management at Term and Late Preterm Birth: A Meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management at term and late preterm birth. OBJECTIVE: To assess effects of umbilical cord management strategies (clamping timing and cord milking) in infants ≥34 weeks' gestational age. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and trial registries searched July 2019. STUDY SELECTION: Two authors independently assessed eligibility of randomized controlled trials. DATA EXTRACTION: Two authors independently extracted data and assessed evidence certainty (Grading of Recommendations Assessment, Development and Evaluations). RESULTS: We identified 46 studies (9159 women and their infants) investigating 7 comparisons. Compared with early cord clamping (ECC) <30 seconds, delayed cord clamping (DCC) ≥30 seconds (33 studies), intact-cord milking (1 study), and cut-cord milking (2 studies) probably improve hematologic measures but may not affect survival without neurodisability, anemia in early infancy, or maternal postpartum hemorrhage. No differences in major neonatal morbidities are seen in studies comparing methods of optimizing placental transfusion (DCC versus cut-cord milking [3 studies], longer delays in clamping [7 studies], or physiologic parameters [3 studies]). Strategies that promote increased placental transfusion may be associated with greater phototherapy use. Evidence for all outcomes was low or very low certainty. LIMITATIONS: Incompleteness and low certainty of findings limit applicability. CONCLUSIONS: Compared with ECC, DCC or cord milking increases hemoglobin and hematocrit immediately after birth in infants ≥34 weeks' gestational age. The uncertain effects of DCC and cord milking compared with ECC on major morbidities limit usefulness of available evidence for policy and practice.

Magnetic Non-invasive Auricular Acupuncture During Eye-Exam for Retinopathy of Prematurity in Preterm Infants: A Multicentre Randomized Controlled Trial.

Background: Eye exam for Retinopathy of prematurity (ROP) is a painful procedure and pharmacological analgesia might be ineffective. We hypothesized that magnetic auricular acupuncture (MAA) compared to placebo will decrease pain during ROP exam in preterm infants. Methods: Multicentre randomized controlled trial conducted in three hospitals (Australia, Canada, and Malaysia). Eligibility: >32 weeks, ROP exam, not sedated, and parental consent. A total of 100 infants were randomized (1:1) to MAA (n = 50) or placebo (n = 50). MAA stickers or placebo were placed on both ears by an unblinded investigator. Pain was assessed using the Premature Infant Pain Profile. Primary analyses were by intention-to-treat. ClinicalTrials.gov:NCT03650621. Findings: The mean (standard deviation, SD) gestation, birthweight, and postnatal age were (MAA 28(3) vs. placebo 28(2) weeks; MAA 1,057(455) vs. placebo 952(273) g; MAA 7(3) vs. placebo 7(3) weeks. Placebo infants had significantly higher PIPP scores during [mean difference 1.6 points (95%CI 0.1-3.1)] and 1 h mean difference 1.5 points (95%CI 0.7-2.2) after the procedure (p < 0.03). Heart rate was lower (173(22) vs. 184(18)/min) and oxygen saturations were higher (93.8(6.2) vs. 91.7(6.1)%, p = 0.05) in MAA infants. No adverse effects. Interpretation: MAA may reduce physiological pain responses during and after ROP exam in preterm infants. Assessment of long-term effects are warranted. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03650621.

Invasive and non-invasive acupuncture techniques for pain management in neonates: a systematic review.

BACKGROUND: Neonatal pain is an extensive research field and there are many possibilities to treat pain in neonates. Acupuncture is one new and non-pharmacological option and a promising tool to reduce pain in neonates undergoing minor painful interventions during routine medical care. OBJECTIVES: This review summarises trials of acupuncture for pain reduction in neonates undergoing painful interventions during routine medical care. DATA SOURCE: MEDLINE, Embase, CINAHL, electronic clinical trials registry platforms and reference lists were systematically screened for trials from their dates of inception to February 2017 (English language database search). STUDY SELECTION: Inclusion criteria were (1) preterm or term neonates, (2) acupuncture for painful medical interventions and (3) formal pain assessment as a primary or secondary study outcome. We included only randomised controlled trials. DATA EXTRACTION: Data were extracted using a standardised protocol and individual risk of bias was assessed. RESULTS: The literature search revealed a total of 12 196 records. After application of inclusion criteria, five studies were included in this review. Two studies demonstrated significant pain reduction, one found equal outcomes in comparison to standard care, and two showed significantly higher pain scores with acupuncture alone. LIMITATIONS: The main limitation of the results is the heterogeneity across trials in acupuncture modality, acupuncture point selection, control groups and pain assessment (heterogeneity: I2=87%). CONCLUSION: The results of this review suggest that acupuncture may have a positive pain-relieving effect in neonates. However, due to the low number of available high-quality trials and heterogeneity across the studies it is not possible to state clear recommendations.

Magnetic noninvasive acupuncture for infant comfort (MAGNIFIC) - a single-blinded randomised controlled pilot trial.

AIM: To determine the safety and feasibility of auricular noninvasive magnetic acupuncture (MA) to decrease infant pain during heel pricks. METHODS: Infants requiring heel pricks for blood collection were randomised to either MA (n = 21) or placebo (P) (n = 19) after parental informed consent. MA or placebo stickers were placed on both ears according to the Battlefield Protocol by an unblinded investigator and left on for 3 days. Pain was assessed with the Premature Infant Pain Profile (PIPP) by blinded clinicians. RESULTS: Mean gestation (MA:34.1, P:34.4 weeks) and age of infants (MA:5.3, P:4.5 days) were similar as were mean (SD) pre (MA:1.7(1.4), P:2.1(1.9)) and post (MA:1.6(1.4), P: 2.1(1.7)) heel prick PIPP scores. PIPP scores were significantly lower in MA infants during heel pricks (MA:5.9(3.7), P: 8.3(4.7), p = 0.04). One-way ANCOVA modelling showed that MA was significantly associated with lower PIPP scores after controlling for analgesic use (p = 0.043). No differences in heart rate, oxygen saturation, analgesic use or adverse effects (e.g. local skin reactions) noted. CONCLUSION: This pilot study shows that auricular MA is feasible in neonates and may reduce PIPP scores during heel pricks. Further study is required to determine the impact of MA on other painful or stressful conditions and on neurodevelopment.

Active Somatic and Psychic Ear Acupuncture Points in Newborn Infants with Neonatal Abstinence Syndrome.

BACKGROUND: Neonatal abstinence syndrome (NAS) occurs within the first days after birth in newborns of mothers with a history of drug abuse. It may also occur in newborns whose mothers are undergoing substitution therapy. OBJECTIVE: To determine the presence of active ear acupuncture points in newborn infants with NAS. METHODS: Among newborn infants with NAS admitted to the Division of Neonatology at the University Hospital Graz between March 2009 and November 2014, an acupuncture-point detector (PS3 Silberbauer, Vienna, Austria) was used to identify active ear acupuncture points. An integrated optical and acoustical signal detects the ear points, which were then assigned to the ear map. A total of 31 newborn infants were assessed; 1 infant was excluded, however, because the mother had already weaned herself off opiates before admission. RESULTS: The excluded infant did not develop signs of NAS, had a low Finnegan score (3 points), and did not present any detectable active psychic ear acupuncture points. In all included newborn infants with NAS, active ear acupuncture points were identified: The psychovegetative rim was the most common active somatic area in each infant, followed by a few somatic and psychic ear acupuncture points. In all infants with symptoms of NAS, active psychic ear points were identified, of which the most frequently found points were the Frustration point and the R point. CONCLUSION: The activity of psychic ear acupuncture points may be specific for neonates with NAS.

Myocardial perfusion and oxidative stress after 21% vs. 100% oxygen ventilation and uninterrupted chest compressions in severely asphyxiated piglets.

AIM: Despite the minimal evidence, neonatal resuscitation guidelines recommend using 100% oxygen when chest compressions (CC) are needed. Uninterrupted CC in adult cardiopulmonary resuscitation (CPR) may improve CPR hemodynamics. We aimed to examine 21% oxygen (air) vs. 100% oxygen in 3:1 CC:ventilation (C:V) CPR or continuous CC with asynchronous ventilation (CCaV) in asphyxiated newborn piglets following cardiac arrest. METHODS: Piglets (1-3 days old) were progressively asphyxiated until cardiac arrest and randomized to 4 experimental groups (n=8 each): air and 3:1 C:V CPR, 100% oxygen and 3:1 C:V CPR, air and CCaV, or 100% oxygen and CCaV. Time to return of spontaneous circulation (ROSC), mortality, and clinical and biochemical parameters were compared between groups. We used echocardiography to measure left ventricular (LV) stroke volume at baseline, at 30min and 4h after ROSC. Left common carotid artery blood pressure was measured continuously. RESULTS: Time to ROSC (heart rate ≥100min(-1)) ranged from 75 to 592s and mortality 50-75%, with no differences between groups. Resuscitation with air was associated with higher LV stroke volume after ROSC and less myocardial oxidative stress compared to 100% oxygen groups. CCaV was associated with lower mean arterial blood pressure after ROSC and higher myocardial lactate than those of 3:1 C:V CPR. CONCLUSION: In neonatal asphyxia-induced cardiac arrest, using air during CC may reduce myocardial oxidative stress and improve cardiac function compared to 100% oxygen. Although overall recovery may be similar, CCaV may impair tissue perfusion compared to 3:1 C:V CPR.

Laser Acupuncture for Neonatal Abstinence Syndrome: A Randomized Controlled Trial.

BACKGROUND: Neonatal abstinence syndrome (NAS) is usually treated with opiate derivatives and supported with nonpharmacological treatment. METHODS: This prospective, randomized, controlled, blinded, single-center study was carried out between March 2009 and November 2014. Newborn infants diagnosed with NAS after maternal opioid substitution therapy were eligible for inclusion. Infants were randomly allocated to the acupuncture group (combining laser acupuncture and pharmacological therapy of morphine and phenobarbital) or control group (pharmacological therapy alone). Laser acupuncture was performed with a LABpen MED 10 (675 nm/10 mW) at 5 ear and 4 body acupuncture points, bilaterally, and sessions were repeated every day. The primary outcome measure was duration of oral morphine therapy for NAS. Secondary outcomes included highest single Finnegan score, time to highest single Finnegan score, maximum amount of oral morphine solution (in milliliters per kilogram and milligrams per kilogram), time to maximum amount of oral morphine solution, and length of hospital stay. RESULTS: Twenty-eight newborns (14 in each group) were eligible for analysis. Duration of oral morphine therapy was significantly reduced in the acupuncture group compared with the control group (28 vs 39 days, respectively, P = .019). In addition, we observed a significantly reduced length of hospital stay in the acupuncture group compared with the control group (35 days [interquartile range 25 to 47] vs 50 days [36 to 66], P = .048). CONCLUSIONS: Adjunctive laser acupuncture significantly reduced the duration of morphine therapy in newborns with NAS.

Acupuncture in the treatment of infantile colic.

Regarding the recently published review "Looking for new treatments of Infantile Colic" by Savino et al. we want to add that positive effects of acupuncture have been demonstrated to release pain and agitation and that acupuncture seems to be a safe treatment when performed by trained acupuncturists. Inconclusive results in the few published articles on the subject can be due to different acupuncture points, different insertion time, different needling methods, differences in the outcome variables, in how the crying was measured and insufficient sample sizes. Further research is needed on understanding the utility, safety, and effectiveness of acupuncture in infants with colic.

Efficacy and safety of acupuncture in preterm and term infants.

The aim of the paper was to review the literature about safety and efficiency of acupuncture therapy in term and preterm infants. We searched Medline, EMBASE, and Cochrane Central Register of Controlled Trials using a predefined algorithm, reviewed abstracts from the Pediatric Academic Society annual meetings (2000-2012), and performed a manual search of references in narrative and systematic reviews. A total of 26 studies identified met our search criteria. Only 6 of these studies met our inclusion criteria; however, two studies had to be excluded because the manuscripts were published in Chinese. Hence, only four studies were included in our analysis. Three of the four studies evaluated the effects of acupuncture on infantile colic, and one assessed pain reduction during minor painful procedures in preterm babies. The limited data available suggests that acupuncture could be a safe nonpharmacologic treatment option for pain reduction in term and preterm infants and could also be a non-pharmacologic treatment option to treat infantile colic. Currently acupuncture in infants should be limited to clinical trials and studies evaluating short- and long-term effects and should be performed only by practitioners with adequate training and experience in neonatal/pediatric acupuncture.

Near-infrared spectroscopy for objectifying cerebral effects of laser acupuncture in term and preterm neonates.

Laser acupuncture (LA) becomes more and more relevant in neonates and infants. With near-infrared spectroscopy (NIRS), a continuous and noninvasive measurement of tissue oxygenation is possible. Aim was to investigate, whether the application of LA was associated with any changes in regional cerebral oxygen saturation (rcSO2) in term and preterm neonates. The study included 20 neonates (12 males, 8 females). The Large Intestine 4 acupuncture point (LI 4, Hegu) was stimulated by a microlaser needle (10 mW, 685 nm laser needle EG GmbH, Germany) for 5 minutes, bilaterally. All neonates underwent polygraphic recording during undisturbed daytime sleep, including heart rate (HR), peripheral oxygen saturation (SpO2), and measurement of nasal flow. Using NIRS, rcSO2 was measured continuously. Cerebral fractional tissue oxygen extraction (cFTOE) was calculated. We did not observe any significant changes in SpO2 and HR values during the whole observation period. However, there was a significant decrease in rcSO2 (P = 0.003) within postintervention period, accompanied by a significant increase in cFTOE (P = 0.010) in postintervention period.