Effect of delayed cord clamping on stem cell transfusion and hematological parameters in preterm infants with placental insufficiency: a pilot randomized trial
Eur J Pediatr. 2020
The feasibility of delayed cord clamping (DCC) in preterm infants with placental insufficiency (PI) is questionable. We aimed to study the effect of DCC on stem cell transfusion, hematological parameters, and clinical outcomes in preterm infants born to mothers with PI. Preterm infants, < 34 weeks' gestation, born to mothers with PI were randomized based on the timing of umbilical cord clamping into delayed clamping for 60 s (DCC group) or immediate cord clamping (ICC group) groups at time of birth. CD34 percentage as a marker of stem cell transfusion, early and late-onset anemia, hypothermia, hypotension, polycythemia, hyperbilirubinemia, duration of oxygen therapy, bronchopulmonary dysplasia, intra-ventricular hemorrhage, necrotizing enterocolitis, sepsis, mortality, and length of hospital stay were compared between studied groups. We found that peripheral blood CD34 percentage was significantly higher in DCC compared with that in the ICC group (median (IQR) of 0.5 (0.40-0.7) versus 0.35 (0.20-0.5), p = 0.004). Infants in the DCC group had significantly lower episodes of anemia of prematurity at 2 months, red blood cell transfusion, and shorter duration of oxygen therapy compared with those in the ICC group.Conclusion: In conclusion, DCC compared with ICC increased stem cell transfusion and decreased early- and late-onset anemia in preterm infants with placental insufficiency.Trial registration: NCT03731546 www.clinicaltrials.gov What is Known: * Delayed cord clamping has been recommended by the American Academy of Pediatrics as a standard of care practice during delivery of preterm infants. * The feasibility of DCC in preterm infants with placental insufficiency (PI) is uncertain. What is New: * This randomized controlled trial demonstrated that DCC in the delivery room care of preterm infants born to mothers with placental insufficiency increased stem cell transfusion and decreased early- and late-onset anemia.
"Fenofibrate as an adjuvant to phototherapy in pathological unconjugated hyperbilirubinemia in neonates: a randomized control trial."
Journal of perinatology : official journal of the California Perinatal Association. 2020
BACKGROUND Despite widespread phototherapy usage, many new-born infants remain in need of other invasive lines of therapy, such as intravenous immunoglobulins and exchange transfusions. OBJECTIVE Assessment of the efficacy and the safety of adding fenofibrate to phototherapy for the treatment of pathological jaundice in full-term infants. DESIGN/METHODS We conducted a double blinded randomized control study on 180 full-term infants with pathological unconjugated hyperbilirubinemia admitted to the NICU at Mansoura University Children's Hospital. They were randomly assigned to receive either oral fenofibrate 10 mg/kg/day for 1 day or 2 days or placebo in addition to phototherapy. The primary outcome was total serum bilirubin values after 12, 24, 36, 48, and 72 h from intervention. Secondary outcomes were total duration of treatment, need for exchange transfusions and intravenous immunoglobulin, exclusive breast-feeding on discharge, and adverse effects of fenofibrate. This study was registered at www.clinicaltrials.gov (NCT04418180). RESULTS A total of 180 full-term infants were included, 60 in each group. Infants in group I and II showed significant reduction of bilirubin levels at 36, 48, and 72 h from intervention compared to group III, respectively. Fenofibrate administration was associated with significantly shorter duration of phototherapy, shorter hospital stay, and higher frequency of exclusive breast-feeding compared to phototherapy alone. CONCLUSION(S): Fenofibrate as an adjuvant to phototherapy in term neonate with pathological jaundice is well tolerated and associated with significant reduction of serum bilirubin levels, a shorter duration of phototherapy, shorter hospital stay and higher frequency of exclusive breast-feeding, without significant adverse effects in either the single or double dosage.
Head midline position for preventing the occurrence or extension of germinal matrix-intraventricular haemorrhage in preterm infants
Cochrane Database Syst Rev. 2020;7:Cd012362
BACKGROUND Head position during care may affect cerebral haemodynamics and contribute to the development of germinal matrix-intraventricular haemorrhage (GM-IVH) in very preterm infants. Turning the head toward one side may occlude jugular venous drainage while increasing intracranial pressure and cerebral blood volume. It is suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the infant is cared for in the supine 'head midline' position. OBJECTIVES To assess whether head midline position is more effective than other head positions for preventing (or preventing extension) of GM-IVH in very preterm infants (< 32 weeks' gestation at birth). SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 12 September 2019), Embase (1980 to 12 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 12 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing caring for very preterm infants in a supine head midline position versus a prone or lateral decubitus position, or undertaking a strategy of regular position change, or having no prespecified position. We included trials enrolling infants with existing GM-IVH and planned to assess extension of haemorrhage in a subgroup of infants. We planned to analyse horizontal (flat) versus head elevated positions separately for all body positions. DATA COLLECTION AND ANALYSIS We used standard methods of Cochrane Neonatal. For each of the included trials, two review authors independently extracted data and assessed risk of bias. The primary outcomes were GM-IVH, severe IVH, and neonatal death. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS Three RCTs, with a total of 290 infants (either < 30 weeks' gestational age or < 1000 g body weight), met the inclusion criteria. Two trials compared supine midline head position versus head rotated 90 degrees with the cot flat. One trial compared supine midline head position versus head rotated 90 degrees with the bed tilted at 30 degrees . We found no trials that compared supine versus prone midline head position. Meta-analysis of three trials (290 infants) did not show an effect on rates of GM-IVH (RR 1.11, 95% confidence interval (CI) 0.78 to 1.56; I(2) = 0%) and severe IVH (RR 0.71, 95% CI 0.37 to 1.33; I(2) = 0%). Neonatal mortality (RR 0.49, 95% CI 0.25 to 0.93; I(2) = 0%; RD -0.09, 95% CI -0.16 to -0.01) and mortality until hospital discharge (typical RR 0.50, 95% CI 0.28 to 0.90; I(2) = 0%; RD -0.10, 95% CI -0.18 to -0.02) were lower in the supine midline head position. The certainty of the evidence was very low for all outcomes because of limitations in study design and imprecision of estimates. We identified one ongoing study. AUTHORS' CONCLUSIONS We found few trial data on the effects of head midline position on GM-IVH in very preterm infants. Although meta-analyses suggest that mortality might be reduced, the certainty of the evidence is very low and it is unclear whether any effect is due to cot tilting (a co-intervention in one trial). Further high-quality RCTs would be needed to resolve this uncertainty.
Effect of Aspiration and Evaluation of Gastric Residuals on Intestinal Inflammation, Bleeding, and Gastrointestinal Peptide Level
The Journal of pediatrics. 2019
OBJECTIVE To determine the effect of gastric residual aspiration and evaluation on preterm very low birth weight infants' gastrointestinal function, intestinal inflammation, and gastrointestinal mucosal bleeding. STUDY DESIGN This single-center, randomized trial compared omission of gastric residuals vs prefeed gastric residuals in 143 infants ≤32 weeks of gestation with a birthweight of ≤1250 g for 6 weeks after birth. Serum levels of gastrin and motilin were collected between 14 and 21 days of life. Stools were collected at 3 and 6 weeks of age and analyzed for calprotectin and S100A12 levels. All stools were tested for occult blood for 6 weeks. RESULTS Means for gastrin (P = .999) and motilin (P = .694) were similar between groups and there were no statistically significant differences in adjusted means for transformed calprotectin (P = .580), and S100A12 (P = .212). Both calprotectin (P = .003) and S100A12 (P = .002) increased from week 3 to week 6. The mean percentage of stools positive for occult blood (P = .888) were similar between the groups. CONCLUSIONS Gastrointestinal function, intestinal inflammation, and gastrointestinal mucosal bleeding were similar whether aspiration and evaluation of gastric residuals were eliminated or not, suggesting routinely evaluating gastric residuals before every feeding may be unnecessary. TRIAL REGISTRATION CLINICALTRIALS.GOV:: NCT01863043.
What clinical practice strategies have been shown to decrease incidence rates of intraventricular haemorrhage in preterm infants?
Journal of paediatrics and child health. 2019;55(10):1269-1278
AIM: To answer the clinical question 'In infants about to be delivered and admitted to neonatal units, what clinical practice strategies, compared to standard care, have been shown to decrease incidence rates of intraventricular haemorrhage (IVH)?' METHODS MEDLINE via Ovid (1943 to 5 January 2018), Embase via Ovid (1974 to 5 January 2018) and the Cochrane Library (5 January 2018) were searched for relevant articles. RESULTS A total of 478 articles, after the removal of duplicates, were found and screened by title and abstract. Forty full-text articles were subsequently reviewed, and 19 were included as relevant to the structured clinical question. An additional article was included based on expert advice. CONCLUSION There are various levels of research evidence for clinical practice strategies to decrease the incidence rates of IVH. Higher-quality evidence suggests that antenatal corticosteroids decrease the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit are associated with decreased rates of IVH.
Infants at high risk of intraventricular haemorrhage (IVH) due to prematurity (20 studies).
Clinical practice strategies to decrease (IVH) incidence rates, including: perinatal and delivery room practices, respiratory and cardiovascular management, and quality improvement strategies.
Higher-quality evidence suggested that antenatal corticosteroids decreased the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit were associated with decreased rates of IVH.
Elevated midline head positioning of extremely low birth weight infants: effects on cardiopulmonary function and the incidence of periventricular-intraventricular hemorrhage
Journal of Perinatology : Official Journal of the California Perinatal Association. 2018;39((1):):54-62.
OBJECTIVE Changes in cerebrovascular hemodynamics associated with head position may be important in the pathogenesis of periventricular-intraventricular hemorrhage (PIVH) in premature infants. This study evaluated the effect of elevated midline head positioning on cardiopulmonary function and the incidence of PIVH. STUDY DESIGN ELBW infants were randomized to FLAT (flat, supine) or ELEV (supine, bed elevated 30 degrees) for 96 h. Cardiopulmonary function, complications of prematurity, and the occurrence of PIVH were documented. RESULTS Infants were randomized into FLAT (n = 90) and ELEV groups (n = 90). No significant differences were seen in the incidence of BPD or other respiratory complications. The ELEV group developed significantly fewer grade 4 hemorrhages (p = 0.036) and survival to discharge was significantly higher in the ELEV group (p = 0.037). CONCLUSIONS Managing ELBW infants in an elevated midline head position for the first 4 days of life appears safe and may decrease the likelihood of severe PIVH and improve survival.
Effect of delayed cord clamping on hematocrit, and thermal and hemodynamic stability in preterm neonates: a randomized controlled trial
Indian Pediatrics. 2017;54((2)):112-115.
OBJECTIVE To evaluate the short term clinical effects of delayed cord clamping in preterm neonates. DESIGN Randomized controlled trial. SETTING A tertiary care neonatal unit from October 2013 to September 2014. PARTICIPANTS 78 mothers with preterm labor between 27 to 316/7 weeks gestation. INTERVENTION Early cord clamping (10 s), delayed cord clamping (60 s) or delayed cord clamping (60 s) along with intramuscular ergometrine (500 microg) administered to the mother. MAIN OUTCOME MEASURES Primary: hematocrit at 4 h after birth; Secondary: temperature on admission in neonatal intensive care unit, blood pressure (non-invasive) at 12 h, and urinary output for initial 72 h. RESULTS Mean (SD) hematocrit at 4 h of birth was 58.9 (2.4)% in delayed cord clamping group, and 58.7 (2.1) % in delayed cord clamping with ergometrine group as compared to 47.6 (1.3) % in early cord clamping group. Mean (SD) temperature on admission in NICU was 35.8 (0.2) masculineC, 35.8 (0.3) masculineC, and 35.5 (0.3) masculineC, respectively in these three groups. The mean (SD) non-invasive blood pressure at 12 h of birth was 45.8 (7.0) mmHg, 45.8 (9.0) mmHg, and 35.5 (8.6) mmHg, respectively in these three groups. Mean (SD) urinary output on day 1 of life was 1.1 (0.2) mL/kg/h, 1.1 (0.2) mL/kg/hr and 0.9 (0.2) ml/kg/h, respectively. CONCLUSION In preterm neonates delayed cord clamping along with lowering the infant below perineum or incision site and administration of ergometrine to mother has significant benefits in terms of increase in hematocrit, higher temperature on admission, and higher blood pressure and urinary output during perinatal transition.
Head midline position for preventing the occurrence or extension of germinal matrix-intraventricular hemorrhage in preterm infants
The Cochrane Database of Systematic Reviews. 2017;((7)):CD012362.
BACKGROUND Preterm birth is known to constitute the major risk factor for development of germinal matrix-intraventricular hemorrhage (GM-IVH). Head position may affect cerebral hemodynamics and thus may be involved indirectly in development of GM-IVH. Turning the head toward one side may functionally occlude jugular venous drainage on the ipsilateral side while increasing intracranial pressure and cerebral blood volume. Thus, it has been suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the patient is in supine midline position with the bed tilted 30 degrees . The midline position might be achieved in the supine position and, with the use of physical aids, in the lateral position as well. Midline position should be kept, at least when the incidence of GM-IVH is greatest, that is, during the first two to three days of life. OBJECTIVES Primary objective To assess whether head midline position is more effective than any other head position for preventing or extending germinal matrix-intraventricular hemorrhage in infants born at ≤ 32 weeks' gestational age. Secondary objectives To perform subgroup analyses regarding gestational age, birth weight, intubated versus not intubated, and with or without GM-IVH at trial entry. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE via PubMed (1966 to September 19, 2016), Embase (1980 to September 19,.2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to September 19, 2016). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA Randomized clinical controlled trials, quasi-randomized trials, and cluster-randomized controlled trials comparing placing very preterm infants in a head midline position versus placing them in a prone or lateral decubitus position, or undertaking a strategy of regular position change, or having no prespecified position. We included trials enrolling infants with existing GM-IVH and planned to assess extension of hemorrhage in a subgroup of infants. We planned to analyze horizontal (flat) versus head elevated positions separately for all body positions. DATA COLLECTION AND ANALYSIS We used standard methods of the Cochrane Neonatal Review Group. For each of the included trials, two review authors independently extracted data (e.g., number of participants, birth weight, gestational age, initiation and duration of head midline position, co-intervention with horizontal vs head elevated position, use of physical aids to maintain head position) and assessed risk of bias (e.g., adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review are GM-IVH , severe IVH, and neonatal death. MAIN RESULTS Our search strategy yielded 2696 references. Two review authors independently assessed all references for inclusion. Two randomized controlled trials, for a total of 110 infants, met the inclusion criteria of this review. Both trials compared supine midline head position with the bed at 0 degrees versus supine head rotated 90 degrees with the bed at 0 degrees . We found no trials that compared supine versus prone midline head position, and no trials that compared effects of head tilting. We found no significant differences in rates of GM-IVH (typical risk ratio [RR] 1.14, 95% confidence interval [CI] 0.55 to 2.35; typical risk difference [RD] 0.03, 95% CI -0.13 to 0.18; two studies, 110 infants; I2 = 0% for RR and I2 = 0% for RD), severe IVH (typical RR 1.57, 95% CI 0.28 to 8.98; typical RD 0.02, 95% CI -0.06 to 0.10; two studies, 110 infants; I2 = 0% for RR and I2 = 0% for RD), and neonatal mortality (typical RR 0.52, 95% CI 0.16 to 1.65; typical RD -0.07, 95% CI -0.18 to 0.05; two studies, 110 infants; I2 = 28% for RR and I2 = 44% for RD). Among secondary outcomes, we f
Effects of umbilical cord milking on the need for packed red blood cell transfusions and early neonatal hemodynamic adaptation in preterm infants born <1500 g: a prospective, randomized, controlled trial
Journal of Pediatric Hematology/Oncology. 2014;36((8):):e493-8.
OBJECTIVE The aim of this study was to evaluate the effects of umbilical cord milking (UCM) on the need for packed red blood cell (PRBC) transfusion and hematologic and hemodynamic parameters in very-low-birth-weight infants. METHODS The infants were randomized into 2 groups: group 1 (UCM) and group 2 (control). The primary outcome was the number of PRBC transfusions during the first 35 days of life. The secondary outcome measures were the hemodynamic variables during the first 24 hours of life. RESULTS A total of 44 infants were included with 22 infants in each group. Two of 21 infants in group 1 and 4 of 21 infants in group 2 received transfusion in the first 3 days of life (P=0.384). The number and volume of PRBC transfusions were similar in both groups. However, the levels of hemoglobin (Hb) at the first and 24th hour of life were significantly higher in group 1. Phlebotomy volume was found as a statistically significant risk factor for the need for PRBC transfusion (P=0.005). CONCLUSIONS UCM in delivery room results in a higher Hb level in the first day of life. In these groups of infants, phlebotomy losses may impact the transfusion need.
Role of hemocoagulase in pulmonary hemorrhage in preterm infants: a systematic review
Indian Journal of Pediatrics. 2011;78((7):):838-44.
Pulmonary hemorrhage (PH) in neonates is associated with significant morbidity and mortality. Hemocoagulase is an established hemostatic agent and may be beneficial in neonates with severe PH.This systematic review was performed to investigate the clinical efficacy and safety of hemocoagulase therapy in preterm infants with Pulmonary hemorrhage (PH). The search strategy of the Cochrane Neonatal Review Group was used to determine outcomes following PH in neonates. The primary outcomes were mortality, duration of PH and length of mechanical ventilation. Other morbidities included: Respiratory Distress Syndrome, sepsis, intraventricular hemorrhage, necrotizing enterocolitis and bronchopulmonary dysplasia. The Cochrane Library, MEDLINE, EMBASE and CINAHL and bibliographies of identified trials were searched. The standard methods of the Cochrane Neonatal Review Group and van Tulder's guidelines were followed independently by the authors to assess study quality, enter data and report outcomes. Typical treatment effects were calculated using fixed confidence intervals (CI). Heterogeneity tests were performed. Two 'randomized' controlled studies related to the role of hemocoagulase in neonates were identified: One for treatment of PH and the other for prevention of PH. All preterm infants' of gestational age<=32 weeks and birth weight<=1500 g with PH were included in the study. A total of 48 and 72 preterm infants were enrolled and randomized into two groups in trial 1 and trial 2 respectively. Mortality risk was significantly lower in the treatment group (RR 0.52; 95%CI 0.31, 0.89, p<0.02) when hemocoagulase was used as therapy compared to prophylactic use in neonates (RR 0.52; 95%CI 0.26, 1.07, p=0.07). Duration of PH and mean duration of ventilation were shorter in both treatment and prophylactic groups. Use of hemocoagulase appeared to be effective in preventing PH in premature infants and reduced mortality. However, the potential risks of use of hemocoagulase including adverse effects and the effectiveness of hemocoagulase still remain uncertain due to the lack of good quality large randomized controlled studies. This needs further evaluation, before routine use can be recommended.