Association of Umbilical Cord Management Strategies With Outcomes of Preterm Infants: A Systematic Review and Network Meta-analysis
JAMA pediatrics. 2021;:e210102
IMPORTANCE It is unclear which umbilical cord management strategy is the best for preventing mortality and morbidities in preterm infants. OBJECTIVE To systematically review and conduct a network meta-analysis comparing 4 umbilical cord management strategies for preterm infants: immediate umbilical cord clamping (ICC), delayed umbilical cord clamping (DCC), umbilical cord milking (UCM), and UCM and DCC. DATA SOURCES PubMed, Embase, CINAHL, and Cochrane CENTRAL databases were searched from inception until September 11, 2020. STUDY SELECTION Randomized clinical trials comparing different umbilical cord management strategies for preterm infants were included. DATA EXTRACTION AND SYNTHESIS Data were extracted for bayesian random-effects meta-analysis to estimate the relative treatment effects (odds ratios [OR] and 95% credible intervals [CrI]) and surface under the cumulative ranking curve values. MAIN OUTCOMES AND MEASURES The primary outcome was predischarge mortality. The secondary outcomes were intraventricular hemorrhage, severe intraventricular hemorrhage, need for packed red blood cell transfusion, and other neonatal morbidities. Confidence in network meta-analysis software was used to assess the quality of evidence and grade outcomes. RESULTS Fifty-six studies enrolled 6852 preterm infants. Compared with ICC, DCC was associated with lower odds of mortality (22 trials, 3083 participants; 7.6% vs 5.0%; OR, 0.64; 95% CrI, 0.39-0.99), intraventricular hemorrhage (25 trials, 3316 participants; 17.8% vs 15.4%; OR, 0.73; 95% CrI, 0.54-0.97), and need for packed red blood cell transfusion (18 trials, 2904 participants; 46.9% vs 38.3%; OR, 0.48; 95% CrI, 0.32-0.66). Compared with ICC, UCM was associated with lower odds of intraventricular hemorrhage (10 trials, 645 participants; 22.5% vs 16.2%; OR, 0.58; 95% CrI, 0.38-0.84) and need for packed red blood cell transfusion (9 trials, 688 participants; 47.3% vs 32.3%; OR, 0.36; 95% CrI, 0.23-0.53), with no significant differences for other secondary outcomes. There was no significant difference between UCM and DCC for any outcome. CONCLUSIONS AND RELEVANCE Compared with ICC, DCC was associated with the lower odds of mortality in preterm infants. Compared with ICC, DCC and UCM were associated with reductions in intraventricular hemorrhage and need for packed red cell transfusion. There was no significant difference between UCM and DCC for any outcome. Further studies directly comparing DCC and UCM are needed.
Feeding Practices and Effects on Transfusion-Associated Necrotizing Enterocolitis in Premature Neonates
Advances in neonatal care : official journal of the National Association of Neonatal Nurses. 2021
BACKGROUND Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. PURPOSE To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. METHODS/SEARCH STRATEGY Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. FINDINGS Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. IMPLICATIONS FOR PRACTICE To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. IMPLICATIONS FOR RESEARCH It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.
Evaluation of high-dose aspirin elimination in the treatment of Kawasaki disease in the incidence of coronary artery aneurysm
Annals of pediatric cardiology. 2021;14(2):146-151
BACKGROUND Standard first-step therapy for Kawasaki disease consists of Intravenous immunoglobulin and high dose Aspirin (80-100 mg/kg/day). The standard dose of Intravenous immunoglobulin (2gr/kg) is strongly effective in reducing the risk of coronary arteries abnormalities. So, the proper dose and efficacy of Aspirin to decrease the risk of coronary arteries abnormalities is a controversial issue. In this study, it is tried to assess the result of eliminating high-dose Aspirin in the treatment of the acute phase of Kawasaki and observe the incidence rate of coronary arteries abnormalities when only Intravenous immunoglobulin was administered. METHODS This study is a prospective randomized, open-label, blinded end-points clinical trial performed in Afzalipour hospital in Kerman University of Medical Sciences from September 2017 to September 2018 in 62 patients with typical and atypical Kawasaki disease. The study group received Intravenous immunoglobulin (2 g/kg) and the control group get the same dose of Intravenous immunoglobulin plus Aspirin with the dose of 80-100 mg/Kg/day until they were afebrile for 48 hours. Afterward, both groups received a daily single dose (3-5 mg/kg) of Aspirin for six weeks. Echocardiography was done after two weeks, six weeks, and six months. Internal diameter of the left and right main coronary arteries was measured and then the corresponding Z-score was calculated. RESULTS In the study group, coronary arteries abnormalities decreased from 38.7% in the 2nd week to 16.1% in the 6th month. In the control group, it declined from 54.8% to 22.6%. There was no statistically significant difference between the groups in term of frequency of abnormal coronary arteries at the study period (P=0.151). CONCLUSIONS We concluded that high dose Aspirin does not have a significant role in preventing coronary arteries abnormalities in Kawasaki disease and giving standard 2 gr/kg/day Intravenous immunoglobulin without high-dose Aspirin in acute-phases therapy does not increase the risk of coronary arteries abnormality.
Effects of timing of umbilical cord clamping on preventing early infancy anemia in low-risk Japanese term infants with planned breastfeeding: a randomized controlled trial
Maternal health, neonatology and perinatology. 2021;7(1):5
BACKGROUND Japanese infants have relatively higher risk of anemia and neonatal jaundice. This study aimed to assess the effects of delayed cord clamping (DCC) on the incidence of anemia during early infancy in low-risk Japanese term infants with planned exclusive breastfeeding for 4 months. This study also aimed to explore the effects of DCC on neonatal jaundice. METHODS We conducted an open-label, parallel-arm, multicenter randomized controlled trial of DCC (clamping the cord after more than a minute or pulsation stops) vs. early cord clamping (ECC; clamping the cord within 15 s) at one birth center and two clinics in Japan. Low-risk pregnant women planning to have a vaginal birth and to exclusively breastfeed and term singleton infants delivered in cephalic presentation were included in this study. The primary outcome was spectrophotometric estimation of hemoglobin at 4 months. Secondary outcomes were anemia incidence at 4 months, four outcomes related to neonatal jaundice, hematocrit levels, and related outcomes. RESULTS Overall, 150 pregnant women were recruited. Participants (N = 138) were randomly allocated to two groups (DCC n = 68, ECC n = 70). There were no significant differences between the two groups in spectrophotometric estimation of hemoglobin at 4 months: mean difference = 0.1 g/dL, 95% confidence interval - 0.14, 0.35, DCC 12.4 g/dL, ECC 12.3 g/dL. Only the hematocrit levels on days 3 to 5 were significantly higher in the DCC group than in the ECC group: DCC 57.0%, ECC 52.6%, mean difference = 4.4, 95% confidence interval 2.61, 6.20. There were no significant differences in other secondary outcomes, including outcomes related to neonatal jaundice. CONCLUSION Among low-risk Japanese term infants with planned exclusive breastfeeding, DCC showed no significant effects on spectrophotometric hemoglobin levels at 4 months compared with ECC. We observed significantly higher hematocrit levels on days 3 to 5 in infants who underwent DCC, while these levels were within the normal range. Jaundice outcomes remained similar to those of infants who underwent ECC. Although a larger sample size is required to assess the effects of cord clamping on neonatal jaundice, DCC may prevent anemia in newborn infants. TRIAL REGISTRATION UMIN-CTR; UMIN000022573, 06/01/2016 - retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000023056.
The Impact of Erythropoietin on Short and Long-term Kidney-Related Outcomes in Extremely Low Gestational Age Neonates. Results of a Multi-center Double-Blind Placebo-Controlled Randomized Clinical Trial
The Journal of pediatrics. 2021
OBJECTIVE To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs. placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22-26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73m2, 35.8% had urine albumin/creatinine ratio (ACR) > 30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (p<0.04). This association remained even after controlling for gestational age, site and sibship (adjusted OR=0.6 [95% CI=0.39-0.92]). We did not find statistically significant differences between treatment groups in eGFR, ACR, rates of SBP >95th percentile or DBP >90th or >95th percentiles. CONCLUSIONS ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months cGA. Recombinant erythropoietin (rhEpo) may protect ELGANs against long-term elevated SBP, but does not appear to protect from AKI, low eGFR, albuminuria or elevated DBP at 22-26 months cGA.
Is fresh, leucodepleted, whole blood transfusion superior to blood component transfusion in pediatric patients undergoing spinal deformity surgeries? A prospective, randomized study analyzing postoperative serological parameters and clinical recovery
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2021;:1-7
PURPOSE To compare the effectiveness of fresh whole blood (FWB) and blood component transfusion in improving clinical outcome and serological parameters in the early postoperative period following spinal deformity surgery. METHODS Patients undergoing major spinal deformity surgeries involving ≥ 6 levels of fusion and expected blood loss ≥ 750 ml between September 2017 and August 2018 were included in the study. The patients were randomized into two groups: FWBG and CG, receiving fresh whole blood and component transfusions, respectively. RESULTS A total of 65 patients with spinal deformities of different etiologies were included. The mean age was 14.0 and 14.9 years in FWB and CG, respectively. All other preoperative parameters were comparable. The mean fusion levels and surgical time were 11.1 and 221.20 min in FWB, as compared with 10.70 and 208.74minutes in CG, respectively. Intraoperative blood losses were 929 ml (FWBG) and 847 ml(CG), and the mean volumes of transfusion were 1.90 (FWBG) and 1.65 units (CG). FWBG was significantly superior to CG in the following clinical and laboratory parameters: duration of oxygen dependence [36.43 (FWBG) vs. 43.45 h (CG); P = 0.0256], mean arterial pH [7.442 (FWBG) vs. 7.394 (CG); p < 0.001], interleukin-6 [30.04 (FWBG) vs. 35.10 (CG); p < 0.019], mean duration of HDU stay [40.6 hours (FWBG) vs 46.51 hours (CG); p = 0.0234] and postoperative facial puffiness [7/30 in FWBG vs. 18/35 (CG) (P < 0.02)]. CONCLUSION FWB transfusion can potentially improve the immediate postoperative outcome in patients undergoing major spinal deformity surgeries by reducing the duration of intensive care unit stay and oxygen dependence. The other potential benefits of this practice, based on our study, include a reduced inflammatory response (reduced lactate and IL-6) and postoperative facial puffiness. However, further large-scale validation studies in future are necessary to precisely determine the role of FWB in spine surgeries. LEVEL OF EVIDENCE II Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
Paediatric patients undergoing spinal deformity surgery (n= 65).
Fresh whole blood: FWBG group (n= 30).
Component transfusions: CG group (n = 35).
The mean fusion levels and surgical time were 11.1 and 221.20 min in FWB, as compared with 10.70 and 208.74 minutes in CG, respectively. Intraoperative blood losses were 929 ml (FWBG) and 847 ml (CG), and the mean volumes of transfusion were 1.90 (FWBG) and 1.65 units (CG). FWBG was significantly superior to CG in the following clinical and laboratory parameters: duration of oxygen dependence, mean arterial pH, interleukin-6, mean duration of high dependency unit stay and postoperative facial puffiness.
Transfusions and neurodevelopmental outcomes in extremely low gestation neonates enrolled in the PENUT Trial: a randomized clinical trial
Pediatric research. 2021;:1-8
BACKGROUND Outcomes of extremely low gestational age neonates (ELGANs) may be adversely impacted by packed red blood cell (pRBC) transfusions. We investigated the impact of transfusions on neurodevelopmental outcome in the Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial population. METHODS This is a post hoc analysis of 936 infants 24-0/6 to 27-6/7 weeks' gestation enrolled in the PENUT Trial. Epo 1000 U/kg or placebo was given every 48 h × 6 doses, followed by 400 U/kg or sham injections 3 times a week through 32 weeks postmenstrual age. Six hundred and twenty-eight (315 placebo, 313 Epo) survived and were assessed at 2 years of age. We evaluated associations between BSID-III scores and the number and volume of pRBC transfusions. RESULTS Each transfusion was associated with a decrease in mean cognitive score of 0.96 (95% CI of [-1.34, -0.57]), a decrease in mean motor score of 1.51 (-1.91, -1.12), and a decrease in mean language score of 1.10 (-1.54, -0.66). Significant negative associations between BSID-III score and transfusion volume and donor exposure were observed in the placebo group but not in the Epo group. CONCLUSIONS Transfusions in ELGANs were associated with worse outcomes. We speculate that strategies to minimize the need for transfusions may improve outcomes. IMPACT Transfusion number, volume, and donor exposure in the neonatal period are associated with worse neurodevelopmental (ND) outcome at 2 years of age, as assessed by the Bayley Infant Scales of Development, Third Edition (BSID-III). The impact of neonatal packed red blood cell transfusions on the neurodevelopmental outcome of preterm infants is unknown. We speculate that strategies to minimize the need for transfusions may improve neurodevelopmental outcomes.
Interventions to minimize blood loss in very preterm infants-A systematic review and meta-analysis
PloS one. 2021;16(2):e0246353
Blood loss in the first days of life has been associated with increased morbidity and mortality in very preterm infants. In this systematic review we included randomized controlled trials comparing the effects of interventions to preserve blood volume in the infant from birth, reduce the need for sampling, or limit the blood sampled. Mortality and major neurodevelopmental disabilities were the primary outcomes. Included studies underwent risk of bias-assessment and data extraction by two review authors independently. We used risk ratio or mean difference to evaluate the treatment effect and meta-analysis for pooled results. The certainty of evidence was assessed using GRADE. We included 31 trials enrolling 3,759 infants. Twenty-five trials were pooled in the comparison delayed cord clamping or cord milking vs. immediate cord clamping or no milking. Increasing placental transfusion resulted in lower mortality during the neonatal period (RR 0.51, 95% CI 0.26 to 1.00; participants = 595; trials = 5; I2 = 0%, moderate certainty of evidence) and during first hospitalization (RR 0.70, 95% CI 0.51, 0.96; 10 RCTs, participants = 2,476, low certainty of evidence). The certainty of evidence was very low for the other primary outcomes of this review. The six remaining trials compared devices to monitor glucose levels (three trials), blood sampling from the umbilical cord or from the placenta vs. blood sampling from the infant (2 trials), and devices to reintroduce the blood after analysis vs. conventional blood sampling (1 trial); the certainty of evidence was rated as very low for all outcomes in these comparisons. Increasing placental transfusion at birth may reduce mortality in very preterm infants; However, extremely limited evidence is available to assess the effects of other interventions to reduce blood loss after birth. In future trials, infants could be randomized following placental transfusion to different blood saving approaches. Trial registration: PROSPERO CRD42020159882.
A preliminary study of influences of hydroxyethyl starch combined with ulinastatin on degree of edema in newborns with capillary leak syndrome
American journal of translational research. 2021;13(4):2626-2634
OBJECTIVE To analyze the efficacy of hydroxyethyl starch (HES) combined with Ulinastatin (Uti) in the treatment of newborns with capillary leak syndrome (CLS). METHODS A total of 60 newborns with CLS admitted to four hospitals were selected as the study subjects, and were randomly divided into the control group (n = 30) and the observation group (n = 30) in accordance with the random number table. The control group was treated with HES alone, while the observation group was treated with Uti combined with HES. RESULTS At 5 d after treatment, the incidence rates of systemic edema and pulmonary edema, the levels of CRP, NE, and BUN, and the duration for the improvement of systemic edema, pulmonary edema and NICU hospital stay in the control group were superior to those in the observation group, while the 24-h urine output, PaO(2) and MAP levels, the levels of A, SCr, ALT, and IL-10 in the observation group were superior to those in the control group (P < 0.05). After 3 months of follow-up after treatment, the mortality rate of newborns in the observation group (13.33%) was lower than that in the control group (36.67%) (P < 0.05). CONCLUSION HES combined with Uti can effectively alleviate edema, control inflammatory levels, and improve hepatic and renal functions and neonatal survival rate of newborns with CLS.
Anemia and Red Blood Cell Transfusions, Cerebral Oxygenation, Brain Injury and Development, and Neurodevelopmental Outcome in Preterm Infants: A Systematic Review
Frontiers in pediatrics. 2021;9:644462
Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO). Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants. Data Sources: PubMed, Embase, reference lists. Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO. Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively. Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes. Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants.
Preterm infants in neonatal intensive care unit (NICU), (38 studies).
Systematic overview of the impact of anaemia and red blood cell (RBC) transfusions during NICU admission on cerebral oxygenation and neurodevelopmental outcome in preterm infants.
Anaemia resulted in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increased cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes.