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1.
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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2.
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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3.
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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4.
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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5.
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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6.
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.
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7.
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
Shinohara E, Kataoka Y, Yaju Y
Maternal health, neonatology and perinatology. 2021;7(1):5
Abstract
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.
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8.
Delayed cord clamping for prevention of intraventricular hemorrhage in preterm neonates: a randomized control trial
Fariba H, Sharma D, Bahia NJ, Leila S, Farahbakhsh N
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;:1-7
Abstract
BACKGROUND Intraventricular hemorrhage (IVH) is a common condition in preterm neonates and is responsible for substantial adverse neurodevelopmental outcome in preterm neonates. Prevention of IVH is an important intervention for better neurological outcome in these preterm neonates. AIMS AND OBJECTIVE This study aimed to determine whether delayed cord clamping (DCC) was superior to immediate cord clamping (ICC) for the prevention of IVH in preterm neonates. PATIENTS AND METHODS In this two centered prospective double-blind randomized controlled trial, eligible neonates with gestational age from 26 to 34 weeks were randomized to receive either ICC (cord clamped in 10-15 s) or DCC (cord clamped in 30-45 s) groups. The grading and severity of IVH were evaluated by cranial ultrasound scan done on the 3-4th and 7-10th days after birth. RESULTS Among the 148 enrolled neonates, 79 were in the ICC group and 69 were in the DCC group. There was no difference in maternal and neonatal baseline characteristics except the neonates in the DCC group weighed more (ICC 1528.77 ± 365.5 g vs. DCC 1658.11 ± 419.52 g; p = .047) at birth. There was no significant difference in the incidence of any grade of IVH in both groups (ICC 12.8% vs. DCC 14.5%; p = .745). There was a significantly higher incidence of grade I IVH (ICC 2.5% vs. DCC 13%; p = .024) in the DCC group. The incidence of grade II IVH (ICC 5.1% vs. DCC 0%; p = .123); grade III IVH (ICC 3.8% vs. DCC 1.4%; p = .623); and grade IV IVH (ICC 1.3% vs. DCC 0%; p>.999) were comparable between the two groups. The incidence of a significant IVH (grades II, III, and IV) was significantly less in the DCC group (ICC 10.1% vs. DCC 1.4%, p = .036). The mean initial hemoglobin levels were significantly higher in neonates enrolled in DCC (15.41 ± 2.1 vs. 16.46 ± 2.45 g/dL; p = .007). There was a significant reduction in the number of days of hospital stay (ICC 18.78 ± 15.42 vs. DCC 13.21 ± 16.16; p = .002). There was no difference in initial hematocrit, platelet count, maximum bilirubin level, and Apgar score (p>.05). CONCLUSIONS Although there was no reduction in any grade of IVH, the incidence of significant IVH (grades II, III, and IV) was significantly decreased with the use of DCC in preterm neonates. Delayed cord clamping also resulted in a significant increase in birth weight, higher hemoglobin levels, and shorter hospital stays without any increase in the risks of hyper-bilirubinemia, low Apgar score, and neonatal mortality. TRIAL REGISTRY IRCT2014031116936N1, https://www.irct.ir/trial/15707.
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9.
Effect of Umbilical Cord Milking vs Delayed Cord Clamping on Venous Hematocrit at 48 Hours in Late Preterm and Term Neonates: A Randomized Controlled Trial
Mangla MK, Thukral A, Sankar MJ, Agarwal R, Deorari AK, Paul VK
Indian pediatrics. 2020
Abstract
OBJECTIVE To compare the effect of intact umbilical cord milking (MUC) and delayed cord clamping (DCC) on venous hematocrit at 48 (±6) hours in late preterm and term neonates (350/7- 426/7 wk). STUDY DESIGN Randomized trial. SETTING AND PARTICIPANTS All late preterm and term neonates (350/7 - 426/7 wk) neonates born in the labor room and maternity operation theatre of tertiary care unit were included. INTERVENTION We randomly allocated enrolled neonates to MUC group (cord milked four times towards the baby while being attached to the placenta; n=72) or DCC group (cord clamped after 60 seconds; n=72). OUTCOME Primary outcome was venous hematocrit at 48 ((±6) hours of life. Additional outcomes were venous hematocrit at 48 ((±6) hours in newborns delivered through lower segment caesarean section (LSCS), incidence of polycythemia requiring partial exchange transfusion, incidence of hyperbilirubinemia requiring phototherapy, and venous hematocrit and serum ferritin levels at 6 (±1) weeks of age. RESULTS The mean (SD) hematocrit at 48 ((±6) hours in the MUC group was higher than in DCC group [57.7 (4.3) vs. 55.9 (4.4); P=0.002]. Venous hematocrit at 6 ((±1) weeks was higher in MUC than in DCC group [mean (SD), 37.7 (4.3) vs. 36 (3.4); mean difference 1.75 (95% CI 0.53 to 2.9); P=0.005]. Other parameters were similar in the two groups. CONCLUSIONS MUC leads to a higher venous hematocrit at 48 (±6) hours in late preterm and term neonates when compared with DCC.
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10.
Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants
Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S, et al
Jama. 2019;322(19):1877-1886
Abstract
Importance: Umbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation. Objective: To determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping. Design, Setting, and Participants: Noninferiority randomized clinical trial of preterm infants (born at 23-31 weeks' gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018. Interventions: Participants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238). Main Outcomes and Measures: The primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin. Results: Among 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, -2% to 9%]; P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%]; P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks' gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%]; P = .002). Conclusions and Relevance: In this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks' gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulting post hoc nature of the analyses preclude definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT03019367.