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Cut umbilical cord milking (C-UCM) as a mode of placental transfusion in non-vigorous preterm neonates: a randomized controlled trial
Bora, R. L., Bandyopadhyay, S., Saha, B., Mukherjee, S., Hazra, A.
European journal of pediatrics. 2023
Abstract
Routine practice of delayed cord clamping (DCC) is the standard of care in vigorous neonates. However there is no consensus on the recommended approach to placental transfusion in non-vigorous neonates. In this trial, we tried to examine the effect of cut umbilical cord milking (C-UCM) as compared to early cord clamping (ECC) on hematological and clinical hemodynamic parameters in non-vigorous preterm neonates of 30-35 weeks gestation. The primary outcome assessed was venous hematocrit (Hct) at 48 (± 4) hours of postnatal age. The important secondary outcomes assessed were serum ferritin at 6 weeks of age, mean blood pressure in the initial transitional phase along with important neonatal morbidities and potential complications. In this single centre randomized controlled trial, 134 non vigorous neonates of 30-35 weeks gestation were allocated in a 1:1 ratio to either C-UCM (n = 67) or ECC (n = 67). For statistical analysis, unpaired Student t and Chi square or Fisher's exact test were used. The mean Hct at 48 h was higher in the C-UCM group as compared to the control group, 50.24(4.200) vs 46.16(2.957), p < .0001. Also significantly higher was the mean Hct at 12 h, 6 weeks and mean serum ferritin at 6 weeks of age in the milked group (p < .0001). Mean blood pressure at 1 h and 6 h was also significantly higher in the milked arm. Need for transfusion and inotropes was less in the milked group but not statistically significant. No significant difference in potential complications was observed between the groups. Conclusion: C-UCM stabilizes initial blood pressure and results in higher hematocrit and improved iron stores. It can be an alternative to DCC in non-vigorous preterm neonates of 30-35 weeks' gestation. Further large multicentric studies are needed to fully establish its efficacy and safety. Trial registration: CTRI/2021/12/038606; registration date December 14, 2021. What is Known: • DCC is the routinely recommended method of placental transfusion for vigorous neonates but no consensus exist for neonates requiring resuscitation at birth. • C-UCM is easier to perform in non-vigorous neonates but there is paucity of studies in the preterm population. What is New: • C-UCM is effective as well as safe in non-vigorous preterm neonates of 30-35 weeks gestational age. • C-UCM holds promise as an alternative to DCC, especially in resource limited settings and in situations where the later is not feasible.
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Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial
Chaudhary, P., Priyadarshi, M., Singh, P., Chaurasia, S., Chaturvedi, J., Basu, S.
European journal of pediatrics. 2023;:1-11
Abstract
Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate. Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia. Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.
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Premature infants receiving delayed cord clamping with and without cord milking: a randomized control trial
Prachukthum S, Tanprasertkul C, Somprasit C
BMC pediatrics. 2023;23(1):123
Abstract
BACKGROUND Preterm infants often have long hospital stays and frequent blood tests; they often develop anemia requiring multiple blood transfusions. Placental transfusion via delayed cord clamping (DCC) or umbilical cord milking (UCM) helps increase blood volume. We hypothesized umbilical cord milking (UCM), together with DCC, would be superior in reducing blood transfusions. OBJECTIVES To compare the effects of DCC and DCC combined with UCM on hematologic outcomes among preterm infants. METHODS One hundred twenty singleton preterm infants born at 280/7- 336/7 weeks of gestation at Thammasat University Hospital were enrolled in an open-label, randomized, controlled trial. They were placed into three groups (1:1:1) by a block-of-three randomization: DCC for 45 s, DCC with UCM performed before clamping (DCM-B), and DCC with UCM performed after clamping (DCM-A). The primary outcomes were hematocrit levels and number of infants receiving blood transfusions during the first 28 days of life. Intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC) were secondary outcomes. Analyses were performed with an intent-to-treat approach. RESULTS One hundred twenty preterm infants were randomized. There was no statistically significant difference in neonatal outcomes; hematocrit on admission 54.0 ± 5.5, 53.3 ± 6.0, and 54.3 ± 5.8 (p = 0.88), receiving blood transfusions 25%, 20%, and 12.5% (p = 0.24), incidence of NEC 7.5, 0 and 10% (p = 0.78) in the DCC, DCM-B and DCM-A groups, respectively. There were no preterm infants with severe IVH, polycythemia, maternal or neonatal death. CONCLUSION The placental transfusion techniques utilized, DCC and DCC combined with UCM, provided the same benefits for preterm infants born at GA 28 and 33 weeks in terms of reducing the need for RBC transfusions, severities of IVH and incidence of NEC without increasing comorbidity. TRIAL REGISTRATION TCTR20190131002 . Registered 31 January 2019-Retrospectively registered.
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Neonatal outcomes from a randomized controlled trial of maternal treatment of iron deficiency anaemia with intravenous ferumoxytol versus oral ferrous sulfate
Awomolo, A. M., McWhirter, A., Sadler, L. C., Coppola, L. M., Hill, M. G.
American journal of obstetrics & gynecology MFM. 2023;:101063
Abstract
BACKGROUND Anemia in pregnancy is common worldwide and has known maternal risks. The relationship between the types of treatment offered for maternal anemia and the effects on the fetus and newborn are largely uninvestigated. OBJECTIVE Investigate whether maternal treatment with intravenous ferumoxytol compared to oral ferrous sulfate results in an increase in neonatal hematologic and iron indices. These analyses were planned secondary outcomes and post-hoc analysis from the trial with a primary outcome of change in maternal hemoglobin. STUDY DESIGN A randomized controlled trial including 124 participants with anemia by WHO criteria was performed in which participants were allocated in a 1:1 ratio to either 2 infusions of 510mg of intravenous ferumoxytol or 325mg oral ferrous sulfate twice daily. Fetal monitoring was performed during each intravenous iron infusion. Standard univariable statistical techniques were used to compare groups and to investigate associations between maternal and neonatal hemoglobin and iron indices. RESULTS Cord blood hematological parameters were equivalent between groups. Hemoglobin was 15.7g/dL vs 15.4g/dL (p = 0.6) and hematocrit was 50.5% and 49.2% (p=0.4) in those randomized to intravenous ferumoxytol, and oral ferrous sulfate, respectively. Iron studies revealed higher cord blood ferritin concentrations in infants of participants treated with intravenous ferumoxytol (294 vs 186, p = 0.005). There were equivalent iron (158 vs 146, p = 0.4), transferrin (186 vs 196, p=0.4) and total iron binding capacity (246 vs 244, p=1) in neonates of participants receiving intravenous versus oral treatment. There were no effects of the infusions observed on cardiotocography. Gestational age at birth was equivalent between groups. We noted a larger birth weight in neonates of participants treated with intravenous ferumoxytol (3215g vs 3033g, p=0.09), which was not statistically significant. Post hoc analyses revealed a statistically significant correlation between neonatal ferritin and maternal hemoglobin (p=0.006) and neonatal ferritin and maternal ferritin (p=0.017) at admission for delivery. CONCLUSION Neonates born to participants who received intravenous ferumoxytol were born with higher ferritin concentrations in cord blood, at the same gestation with the same birthweight. Participants with higher hemoglobin and ferritin indices delivered infants with higher ferritin concentrations in cord blood.
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Effective management of foetal anaemia in Rh(D) alloimmunised pregnant women with intrauterine transfusion: a Systematic Review
Prescott, B., Jackson, D. E.
Hematology, transfusion and cell therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops. STUDY DESIGN AND METHOD A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method. RESULTS Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present. CONCLUSION The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.
PICO Summary
Population
Rh(D) alloimmunised pregnant women (15 studies).
Intervention
Systematic review and meta-analysis to determine the effectiveness and safety of intrauterine transfusions (IUTs).
Comparison
Outcome
The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present.
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Placental Transfusion Strategies in Preterm Infants in Low- and Middle-Income Countries: A Systematic Review and Network Meta-Analysis
Ramaswamy VV, Bandyopadhyay T, Abiramalatha T, Shaik NB, Pullattayil SAk, Jasani B, Hegde V, Trevisanuto D, Weiner GM
Neonatology. 2022;:1-16
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Editor's Choice
Abstract
INTRODUCTION Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). METHODS Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. RESULTS Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30-60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78-1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01-1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). CONCLUSIONS In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival.
PICO Summary
Population
Preterm newborns in low- and middle-income countries (9 studies).
Intervention
Delayed cord clamping (DCC) for various time intervals.
Comparison
DCC until cord pulsations stop. Umbilical cord milking. Immediate cord clamping (ICC).
Outcome
Network meta-analysis of 9 randomised controlled trials could not rule out benefit or harm for survival from DCC 30-60s compared to ICC: relative risk (RR), (95% credible interval) 0.96 (0.78 to 1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01 to 1.22), very low certainty. Differences were not detected in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60s and 120s might improve the haematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty).
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Bleeding Complications Associated with Pregnancy with Primary Immune Thrombocytopenia: A Meta-Analysis
Gonzalez-Porras JR, Palomino D, Vaquero-Roncero LM, Bastida JM
TH open : companion journal to thrombosis and haemostasis. 2022;6(3):e230-e237
Abstract
Introduction Immune thrombocytopenia (ITP) during pregnancy has received little attention from researchers. Reliable information about the outcome of mothers and newborns is required to properly counsel women who are pregnant or planning to become pregnant. Our primary outcomes were the frequency and severity of maternal and neonatal bleeding events in the setting of ITP in pregnancy. Mode of delivery, neonatal thrombocytopenia, and maternal/infant mortality were secondary outcomes. Material and Methods We comprehensively reviewed the prospective studies that enrolled ≥20 pregnant women with primary ITP. Two reviewers, blinded to each other, searched Medline and Embase up to February 2021. Meta-analyses of the maternal and newborn outcomes were performed. Weighted proportions were estimated by a random-effects model. Results From an initial screening of 163 articles, 15 were included, encompassing 1,043 pregnancies. The weighted event rate for bleeding during pregnancy was 0.181 (95% confidence interval [CI], 0.048-0.494). Most of these were nonsevere cases. The weighted event rates were 0.053 (95% CI, 0.020-0.134) for severe postpartum hemorrhage, 0.014 (95% CI, 0.008-0.025) for intracerebral hemorrhage, and 0.122 (0.095-0.157) for severe thrombocytopenia events in neonates (platelet count <50,000/μL). There were no reliable predictors of severe neonatal thrombocytopenia. The incidence of neonatal mortality was 1.06%. There were no maternal deaths. Conclusion Primary ITP in pregnant women is rarely associated with poor outcomes.
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Effects of spontaneous first breath on placental transfusion in term neonates born by cesarean section: A randomized controlled trial
Kilicdag H, Parlakgumus D, Demir SC, Satar M
Frontiers in pediatrics. 2022;10:925656
Abstract
BACKGROUND The role of umbilical cord management in placental transfusion in cesarean section (CS) requires clarification. The spontaneous first breath may be more important than the timing of cord clamping for placental transfusion in neonates born by CS. OBJECTIVE This study aimed to evaluate the impact of cord clamping after the first spontaneous breath on placental transfusion in neonates born by CS. METHODS We recruited women with a live singleton pregnancy at ≥37.0 weeks of gestation admitted for CS. The interventions performed, such as physiologic-based cord clamping (PBCC), intact-umbilical cord milking (I-UCM), 30-s delay in cord clamping (30-s DCC), and 60-s delay in cord clamping (60-s DCC), were noted and placed in a sealed envelope. The sealed envelope was opened immediately before delivery to perform randomization. RESULTS A total of 123 infants were eligible for evaluation. Of these, 31, 30, 32, and 30 were assigned to the PBCC, I-UCM, 30-s DCC, and 60-s DCC groups, respectively. The mean hemoglobin (Hb) and mean hematocrit (Hct) were significantly higher in the 60-s DCC group than in the PBCC group (p = 0.028 and 0.019, respectively), but no difference was noted among the I-UCM, 30-s DCC, and PBCC groups at 36 h of age. Further, no significant differences were observed in the mean Hb and mean Hct among the I-UCM, 60-s DCC, and 30-s DCC groups. Peak total serum bilirubin (TSB) levels were higher in the 60-s DCC group than in the I-UCM and PBCC groups (p = 0.017), but there was no difference between the 60-s DCC and 30-s DCC groups during the first week of life. The phototherapy requirement was higher in 60-s DCC than in IUCM and 30-sDCC (p = 0.001). CONCLUSIONS Our findings demonstrated that PBCC, 30-s DCC, and I-UCM in neonates born by CS had no significant differences from each other on placental transfusion. The Hb and Hct in the neonates were higher after 60-s DCC than after PBCC.
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Hemostasis in Neonates with Perinatal Hypoxia-Laboratory Approach: A Systematic Review
Tsaousi M, Iliodromiti Z, Iacovidou N, Karapati E, Sulaj A, Tsantes AG, Petropoulou C, Boutsikou T, Tsantes AE, Sokou R
Seminars in thrombosis and hemostasis. 2022
Abstract
Birth asphyxia, with an estimated prevalence of 1 to 6 per 1,000 live births, may lead to multiorgan dysfunction due to impaired oxygen and/or blood supply to various organ systems, including the hemostatic system. Coagulopathy, a common complication of perinatal asphyxia, has been described since the 1960s. The aim of this study was to systematically review the literature for records on the use of hemostasis tests in the evaluation of coagulation disorders, in neonates who had suffered from perinatal hypoxia or asphyxia. We identified published studies by searching PubMed and Scopus, up until April 2022. The literature search retrieved 37 articles fulfilling the inclusion criteria of the review. According to the bibliography, thrombocytopenia is commonly associated with perinatal hypoxia/asphyxia. The thrombocytopenia is usually described as mild and platelets return to normal levels by the 10th day of life. Additionally, hypoxic neonates usually present with a hypocoagulable profile, as reflected by the prolongation of standard coagulation tests, including prothrombin time, activated partial thromboplastin time, and international normalized ratio, findings commonly associated with disseminated intravascular coagulation, and by the reduction of the levels of the physiologic inhibition of coagulation system. A few studies thus far using ROTEM/TEG in hypoxic neonates have come to the same conclusion as well; hypoxic newborns seem to be characterized by a hypocoagulable profile compared with healthy neonates. It should be emphasized, however, that standard coagulation tests provide only a rough estimation of the true bleeding or thrombotic risk of hypoxic neonates. On the contrary, viscoelastic methods seem to be more precise in the early detection of hemostasis disorders in the neonatal population. However, until now, there was uncertainty as to the most appropriate coagulation assays for diagnosis and management of coagulation derangement in neonates with perinatal hypoxia indicating the need for further research on this field.
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Effects of Umbilical Cord Management Strategies on Stem Cell Transfusion, Delivery Room Adaptation, and Cerebral Oxygenation in Term and Late Preterm Infants
Okulu E, Haskologlu S, Guloglu D, Kostekci E, Erdeve O, Atasay B, Koc A, Soylemez F, Dogu F, Ikinciogullari A, et al
Frontiers in pediatrics. 2022;10:838444
Abstract
BACKGROUND The umbilical cord blood contains a high concentration of stem cells. There is not any published study evaluating the amount of stem cells that have the potential to be transferred to the infant through placental transfusion methods as delayed cord clamping (DCC) and umbilical cord milking (UCM). The aim of this study is to measure the concentrations of endothelial progenitor cell (EPC) and CD34+ hematopoietic stem cell (HSC) in the placental residual blood volume (PRBV), and evaluate the delivery room adaptation and cerebral oxygenation of these infants. METHODS Infants with ≥36 gestational weeks were randomized to receive DCC (120 s), UCM, or immediate cord clamping (ICC). EPC and CD34+ HSC were measured by flow cytometry from the cord blood. PRBV was collected in the setup. The cord blood gas analysis and complete blood count were performed. The heart rate (HR), oxygen saturation (SpO2), and cerebral regional oxygen saturation (crSO2) were recorded. RESULTS A total of 103 infants were evaluated. The amount of PRBV (in ml and ml/kg) was higher in the ICC group (p < 0.001). The number of EPCs in the PRBV content (both ml and ml/kg) were the highest in the ICC group (p = 0.002 and p = 0.001, respectively). The number of CD34+ HSCs in PRBV content (ml and ml/kg) was similar in all groups, but nonsignificantly higher in the ICC group. The APGAR scores at the first and fifth min were lower in the ICC group (p < 0.05). The mean crSO2 values were higher at the 3rd and 10th min in the DCC group (p = 0.042 and p = 0.045, respectively). cFOE values were higher at the 3rd and 10th min in the ICC group (p = 0.011 and p < 0.001, respectively). CONCLUSION This study showed that placental transfusion methods, such as DCC and UCM, provide both higher blood volume, more stem cells transfer to the infant, and better cerebral oxygenation in the first minutes of life, whereas many lineages of stem cells is lost to the placenta by ICC with higher residual blood volume. These cord management methods rather than ICC do not require any cost or technology, and may be a preemptive therapeutic source for diseases of the neonatal period.