Immediate versus delayed umbilical cord clamping in premature neonates born < 35 weeks: a prospective, randomized, controlled study

The purpose of this study was to test whether delayed versus immediate cord clamping would result in higher blood pressure (BP) and hematocrit (Hct), and to assess its clinical effects on the neonatal course in premature neonates (< 35 weeks). This was a prospective, masked, randomized, controlled study. Prior to delivery, 35 neonates were randomly assigned to immediate cord clamping (ICC) at 5 to 10 seconds, and a comparable group of 30 neonates were randomly assigned to delayed cord clamping (DCC) at 30 to 45 seconds. Intention-to-treat analyses revealed that the DCC group tended to have higher initial diastolic BP and higher Hct (especially in vaginally delivered neonates). Infants weighing < 1500 g with DCC tended to have higher mean BP, and needed less mechanical ventilation and surfactant compared with ICC neonates. Infants with DCC did not experience more polycythemia (Hct > 60%), but had a trend toward higher bilirubin levels with no differences in the phototherapy needs. DCC seems to be safe and may be beneficial when compared with ICC in premature neonates. However, the differences between the two methods were modest and the clinical relevance needs to be assessed further by larger studies and additional meta-analysis of randomized trials.     

Placental transfusion: umbilical cord clamping and preterm infants.

OBJECTIVE: To investigate the clinical effects of early versus late cord clamping in preterm infants. STUDY DESIGN: A total of 32 premature infants were prospectively randomized. The following parameters were measured: Initial spun hematocrit (Hct), hemoglobin (Hgb), red blood cell (RBC) counts, frequency of blood transfusions, peak serum bilirubin, mean blood pressure (MBP), oxygen index, intraventricular hemorrhage, and significant patent ductus arteriosus (PDA). RESULTS: Over the 4-week study period, the delayed cord clamping (DCC) group exhibited a decrease in the frequency of blood transfusion (p < 0.001) and also a decrease in albumin transfusions over the first 24 hours (p < 0.03). MBP in the first 4 hours was higher in the DCC group (p < 0.01), and there were statistically significant increases in Hct (21%), Hgb (23%), and RBC count (21%) compared with the early cord clamping group. The risks of patent ductus arteriosus, hyperbilirubinemia, or intraventricular hemorrhage were similar in both groups. Late clamping of the umbilical cord had little or no effect on the oxygen index. CONCLUSION: DCC significantly reduced the requirement for blood and albumin transfusion. It also increased the initial Hct, RBC count, Hgb levels, and MBP.     

Delayed cord clamping and inotrope use in preterm infants

Objective: To evaluate the impact of delayed cord clamping (DCC) on need for inotropic support and mean arterial blood pressure (MABP).

Methods: This is a single-center, prospective case-control study of premature infants, born <32 weeks gestation, who underwent DCC in comparison to a matched control group who underwent immediate cord clamping (ICC). The primary outcomes were the differences in MABP and inotropic medication used over the first week of life. Secondary outcomes included the admission hemoglobin, need for blood transfusion, and rates of intraventricular hemorrhage (IVH). Infants were matched on EGA, birth weight, sex, antenatal corticosteroid and magnesium exposure, and presence of chorioamnionitis.

Results: Hundred and fifty-eight infants (DCC n?=?79, ICC n?=?79) were included. Demographic factors were similar between groups. DCC infants had a higher admission hemoglobin (p?p?=?.03), fewer median transfusions (p?=?.03), and were discharged at an earlier post-menstrual age (p?=?.04). When controlling for other factors, DCC was not associated with a reduction in inotrope use (p?=?.22) but was associated with a reduction in high-grade IVH (p?=?.01). There was no difference in MABP between the groups.

Conclusions: DCC is not associated with a reduction in the use of inotropes or a difference in MABP.     

Cord clamping time in spontaneously breathing preterm neonates in the first minutes after birth: impact on cerebral oxygenation – a prospective observational study

Objective: To analyse impact of delayed cord clamping (DCC60sec) on cerebral regional tissue oxygenation (crSO2) and fractional tissue oxygen extraction (cFTOE) in spontaneously breathing preterm neonates during the first 15?min after birth.

Methods: Two-centre observational study, crSO2 and cFTOE was monitored in neonates with DCC60sec or early cord clamping (ECC?<?30?s).

Results: Seventy-six infants (birth weight and gestational age 1736?±?508?g and 31.8?±?2.5 weeks) were included. DCC was associated with lower initial crSO2 and higher cFTOE and lower initial Apgar-score and heart rate.

Conclusion: Attending practitioners should be aware that DCC might impact initial immediate transition in spontaneously breathing preterm neonates.     

延迟脐带结扎对极早产儿的临床意义

目的：评价延迟脐带结扎（delayed cord clamping,DCC）对极早产儿预后的影响。方法：选取2019年5月—2021年5月郑州大学第三附属医院阴道分娩的极早产儿,随机分为早期脐带结扎（early cord clamping,ECC）组和DCC组。比较2组的血常规、胆红素值、Apgar评分、平均动脉压、血气、体温,以及新生儿低氧血症、急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）、输血、脑室内出血、坏死性小肠炎、败血症、低血糖、新生儿死亡、高胆红素血症及光疗的发生率。比较2组极早产儿平均住院日和平均住院费用,并比较2组产妇的第三产程和产后出血量。结果：DCC组极早产儿出生时血红蛋白、72 h血红蛋白、出生时红细胞压积、72 h红细胞压积、平均动脉压、出生时胆红素、胆红素峰值均高于ECC组,差异有统计学意义（P<0.05）。DCC组的新生儿低氧血症、ARDS、输血、脑室内出血、坏死性小肠炎、新生儿败血症、低血糖的发生率,以及极早产儿平均住院日、平均住院费用均低于ECC组,差异有统计学意义（P<0.05）。2组极早产儿的Apgar评分、体温、酸中毒发生率、高胆红素血症发生率、光疗发生率、红细胞增多症发生率及新生儿死亡率比较,差异无统计学意义（P>0.05）。2组产妇的第三产程及产后出血量比较,差异无统计学意义（P>0.05）。结论：DCC是一项可以有效改善极早产儿分娩结局且不增加其他并发症的临床干预措施。     

A systematic review and meta-analysis of a brief delay in clamping the umbilical cord of preterm infants

BACKGROUND: The optimal timing of clamping the umbilical cord in preterm infants at birth is the subject of continuing debate. Objective: To investigate the effects of a brief delay in cord clamping on the outcome of babies born prematurely. METHODS: A retrospective meta-analysis of randomised trials in preterm infants was conducted. Data were collected from published studies identified by a structured literature search in EMBASE, PubMed, CINAHL and the Cochrane Library. All infants born below 37 weeks gestation and enrolled into a randomised study of delayed cord clamping (30 s or more) versus immediate cord clamping (less than 20 s) after birth were included. Systematic search and analysis of the data were done according to the methodology of the Cochrane collaboration. RESULTS: Ten studies describing a total of 454 preterm infants were identified which met the inclusion and assessment criteria. Major benefits of the intervention were higher circulating blood volume during the first 24 h of life, less need for blood transfusions (p = 0.004) and less incidence of intraventricular hemorrhage (p = 0.002). CONCLUSIONS: The procedure of a delayed cord clamping time of at least 30 s is safe to use and does not compromise the preterm infant in the initial post-partum adaptation phase.     

Current best evidence: a review of the literature on umbilical cord clamping

Immediate clamping of the umbilical cord can reduce the red blood cells an infant receives at birth by more than 50%, resulting in potential short-term and long-term neonatal problems. Cord clamping studies from 1980 to 2001 were reviewed. Five hundred thirty-one term infants in the nine identified randomized and nonrandomized studies experienced late clamping, ranging from 3 minutes to cessation of pulsations, without symptoms of polycythemia or significant hyperbilirubinemia. Higher red blood cell flow to vital organs in the first week was noted, and term infants had less anemia at 2 months and increased duration of early breastfeeding. In seven randomized trials of preterm infants, benefits associated with delayed clamping in these infants included higher hematocrit and hemoglobin levels, blood pressure, and blood volume, with better cardiopulmonary adaptation and fewer days of oxygen and ventilation and fewer transfusions needed. For both term and preterm infants, few, if any, risks were associated with delayed cord clamping. Longitudinal studies of infants with immediate and delayed cord clamping are needed.     

Early versus delayed cord clamping in term and preterm births: a review

The optimal timing for cord clamping, early versus delayed, in the third stage of labour is a controversial subject. Issues surrounding the timing of cord clamping include gestational age and maternal and neonatal considerations. Delayed cord clamping (DCC) has been shown to increase placental transfusion, leading to an increase in neonatal blood volume at birth of approximately 30%. In the term infant, although this may result in an increase in iron stores, thereby decreasing the risk of anemia, it may adversely increase the risk of jaundice and the need for phototherapy. In the preterm infant, DCC (or even milking of the cord) decreases the need for blood transfusions for anemia, the number of such transfusions, and the risks of intraventricular hemorrhage and late-onset sepsis. Advantages of DCC also include a reduction in alloimmunization in Rh-negative women, although this advantage is theoretical and unproven. We searched multiple databases including PubMed Clinical Queries, Trip Database, Cochrane Systematic Reviews, and UpToDate, as well as published guidelines from the Society of Obstetricians and Gynaecologists of Canada, the American Congress of Obstetricians and Gynecologists, and the Royal College of Obstetricians and Gynaecologists. We preferentially selected systematic reviews and randomized controlled trials for this literature review. Overall, the available evidence appears to suggest that DCC is likely to result in better neonatal outcomes in both term and preterm infants, even in areas where neonatal iron deficiency anemia is rare. However, there is insufficient evidence to date to support a recommendation to delay cord clamping in non-vigorous infants requiring resuscitation.     

Clamp late and maintain perfusion (CLAMP) policy: delayed cord clamping in preterm infants

Objective: Randomized controlled trials have demonstrated that delayed umbilical cord clamping (DCC) in preterm infants results in improved neonatal outcomes, including increased hematocrit, and decreased rates of intraventricular hemorrhage (IVH) and packed red blood cell transfusions. We hypothesized that implementation of a DCC policy in preterm infants would result in similarly improved outcomes, despite initial clinician resistance.

Study design: A DCC policy (30–60?s) for singleton infants <35 weeks gestation was implemented in September 2011. We conducted a pre-test/post-test analysis of neonatal outcomes among singletons delivered between 24 0/7 weeks and 34 6/7 weeks gestation from 2009 to 2013 (2 years pre-implementation and 2 years post-implementation). The primary outcomes were rates of policy compliance and four neonatal outcomes.

Results: Despite multiple routes of policy dissemination, DCC was attempted in only 49% of the deliveries. In spite of this, infants delivered post-policy implementation (n?=?196) had a significant decrease in IVH, significant increase in initial hematocrits, and improved temperatures compared with infants delivered pre-implementation (n?=?204).

Conclusion: After implementation of a DCC policy, preterm singleton infants had improved temperatures, increased hematocrits and a decreased prevalence of IVH without significant differences in adverse outcomes, suggesting that the benefits of DCC outweighed the risks.     

Effects and safety of delayed versus early umbilical cord clamping in newborns of HIV-infected mothers

Objective: To investigate the effect of a 2 minutes-delayed cord clamp (DCC) versus early cord clamp (ECC) on neonate haemoglobin concentration 24 hours and 1 month after birth, and assess the safety of DCC concerning the risk of HIV infection.

Design: Sixty-four mother-infant peers were enrolled. All mothers were on stable ARV therapy. Viral load, CD4⁺ count and blood haemoglobin (Hb) concentrations 24 hours before delivery were collected from all mothers and their infants.

Methods: All patients were enrolled at the Department of Paediatrics, AO FBF Sacco Hospital in Milan, and were followed until 18 months after birth. Women with haematological diseases and obstetrical complications were excluded. All of 64 mother and infants couples (32 ECC group and 32 DCC group) completed the study. ECC and DCC are defined as application of umbilical clamp within 30 seconds and 120 seconds after birth, respectively.

Results: Mean birth weight was significantly higher in the DCC compared with ECC group. Mean Hb levels at birth were significantly higher in DCC than in ECC group (p?=?.05): this difference persisted at 1 month of life. All newborns showed negative viral load.

Conclusions: DCC 2 minutes after birth is proven to be a safe procedure, particularly beneficial in newborns from HIV mothers. The risk of anemia is significantly decreased at 24 hours after birth and persists at age of 1 month without any increased risk of neonatal jaundice or polycitemia.     

Risk factors of the failure of surfactant treatment by transient intubation during nasal continuous positive airway pressure in preterm infants

We sought to identify risk factors and neonatal outcomes associated with the failure of the INSURE method ( INtubation- SURfactant- Extubation) during nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome. We used a retrospective analysis of the prenatal histories, clinical courses, and laboratory data of all inborn infants with gestational age 27 to 34 weeks and respiratory distress syndrome treated with INSURE method. Infants were categorized into two groups: INSURE failure group and INSURE success group. One hundred nine infants were eligible to the study. INSURE failure was registered in 35 infants (32.1%). After control for confounding variables, INSURE failure was significantly associated with arterial partial pressure of carbon dioxide (adjusted odds ratio [OR] = 1.82; 95% confidence interval [CI] = 1.76 to 90.56), mean arterial-to-alveolar oxygen tension ratio (adjusted OR = 1.13; 95% CI = 1.06 to 85.34) and severe radiological grade (adjusted OR = 1.31; 95% CI = 1.15 to 70.16). Positive predictive values of these variables were 70, 75, and 55%, respectively. Patent ductus arteriosus and mortality rates were significantly higher in INSURE failure group. Arterial partial pressure of carbon dioxide, arterial-to-alveolar oxygen tension ratio, and severe radiological grade are predictors of the failure of INSURE method in preterm infants with respiratory distress syndrome. However, a prospective randomized controlled trial is needed to determine whether or not infants at risk for INSURE failure are better off being treated with mechanical ventilation.     

Effect of placental transfusion on the blood volume and clinical outcome of infants born by cesarean section

Delay in cord clamping up to 30 to 40 seconds is feasible and should be practiced in preterm and term infants born by cesarean section. In term infants, this maneuver may decrease iron deficiency anemia at 6 months of age. Premature infants may have a higher blood volume and hematocrit initially requiring fewer transfusions. They also have a decreased incidence of intraventricular hemorrhage. The effect of compounding factors, such as maternal blood pressure, uterine contraction, medications, bleeding, and their effects on the infant's immediate and long-term outcome are unclear.     

Early neonatal predictors of neonatal hypocalcemia in infants of diabetic mothers: an epidemiologic study

Prematurity, neonatal asphyxia, hypomagnesemia, and advanced maternal diabetes are traditional risk factors for hypocalcemia in infants of diabetic mothers (IDMs). The aim of this study was to determine the relative contribution of these factors separately and combined in a cohort of diabetic pregnancies managed prospectively in the recent 9 years and to find accurate predictors of neonatal hypocalcemia in infants of diabetic mothers. We hypothesized that these factors plus low cord blood calcium (Ca) concentration allow prediction of IDMs who develop neonatal hypocalcemia. We studied 186 IDMs (White class B-RT); gestational age (GA, weeks) was by last menstrual period, confirmed +/- 2 weeks by Ballard score. The goals of glycemic control were: preprandial blood glucose less than 100 mg/dl and 90-minute postprandial blood glucose less than 140 mg/dl. Apgar scores, and cord, 24-, 48- and 72-hour serum calcium (Ca) (mg/dl) and magnesium (Mg; mg/dl) were determined. In univariate analysis, lowest serum Ca correlated with cord blood Ca (r = 0.48, p less than 0.001), GA (r = 0.37, p less than 0.001), and 1-minute Apgar score (r = 0.18, p = 0.09), but did not correlate with cord Mg or with advanced White class. In multiple regression, cord Ca and GA were dominant effects and other variables became insignificant. Lowest Ca (mg/dl) was predicted as follows: lowest Ca = 34.05 - 3.22 (Ca cord) - 0.84 (GA) + 0.10 (GA) (Ca cord). This equation predicts neonatal hypocalcemia (lowest Ca less than 8 mg/dl) with a sensitivity of 72% and a specificity of 75%. Thus, GA and cord Ca allow determination of IDMs at risk for neonatal hypocalcemia.     

A review of benefits of cord milking over delayed cord clamping in the preterm infant and future directions of research

Purpose of review: The recommended method of handling the umbilical cord has undergone a complete 360° turn over the years and current knowledge and research has led the direction to delayed clamping and cord milking. This practice has also been supported by American College of Obstetrics and Gynecology (ACOG) in 2012. This review is a summary of current evidence on delayed cord clamping (DCC), umbilical cord milking (UCM), and comparison between the two and future directions.

Recent findings: Multiple studies have been published establishing the safety of umbilical cord milking. Data comparing UCM to DCC favor milking specifically in terms of improved systemic perfusion and higher hemoglobin concentrations.

Summary: UCM is emerging as a safe, quick alternative to DCC and more advantageous especially among premature infants and those delivered via cesarean section.     

Cochrane Update: Effect of timing of umbilical cord clamping at birth of term infants on mother and baby outcomes

BACKGROUND: Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord greater than one minute after the birth or when cord pulsation has ceased. OBJECTIVES: To determine the effects of different policies of timing of cord clamping at delivery of the placenta on maternal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Child Birth Group's Trials Register (December 2007). SELECTION CRITERIA: Randomized controlled trials comparing early and late cord clamping. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: We included 11 trials of 2,989 mothers and their babies. No significant differences between early and late cord clamping were seen for postpartum hemorrhage or severe postpartum hemorrhage in any of the five trials (2236 women) which measured this outcome (relative risk (RR) for postpartum hemorrhage 500 mls or more 1.22, 95% (CI) 0.96 to 1.55). For neonatal outcomes, our review showed both benefits and harms for late cord clamping. Following birth, there was a significant increase in infants needing phototherapy for jaundice (RR 0.59, 95% CI 0.38 to 0.92; five trials of 1,762 infants) in the late compared with early clamping group. This was accompanied by significant increases in newborn hemoglobin levels in the late cord clamping group compared with early cord clamping (weighted mean difference 2.17 g/dL; 95% CI 0.28 to 4.06; three trials of 671 infants), although this effect did not persist past six months. Infant ferritin levels remained higher in the late clamping group than the early clamping group at six months. AUTHORS' CONCLUSION: One definition of active management includes directions to administer an uterotonic with birth of the anterior shoulder of the baby and to clamp the umbilical cord within 30-60 seconds of birth of the baby (which is not always feasible in practice). In this review delaying clamping of the cord for at least two to three minutes seems not to increase the risk of postpartum hemorrhage. In addition, late cord clamping can be advantageous for the infant by improving iron status which may be of clinical value particularly in infants where access to good nutrition is poor, although delaying clamping increases the risk of jaundice requiring phototherapy.     

Neonatal morbidity in pregnancy complicated by diabetes mellitus: predictive value of maternal glycemic profiles

The relationship between glycemic control and perinatal outcome was assessed in a relatively uniform population of 75 White Class B through D pregnant diabetic women. All patients used glucose reflectance meter self-monitoring and performed a minimum of four determinations daily. Mean capillary blood glucose was calculated from a minimum of 16 weeks of determinations. Regression analysis confirmed a correlation between these values and third-trimester hemoglobin A1 (p less than 0.001). The study population was divided into two groups on the basis of mean capillary blood glucose values: group I, mean capillary blood glucose less than 110 mg/dl (43 patients) (mean = 96.8 +/- 7.1); group II, mean capillary blood glucose greater than 110 mg/dl (32 patients) (mean = 126 +/- 9.0). Of the 32 patients in group II, eight had mean capillary blood glucose greater than or equal to 130 mg/dl. The degree of maternal glycemic control appeared to affect perinatal outcome. At least one form of infant morbidity was present in 33% of group I infants compared with 53% of group II. Significant differences were observed for the incidence of hypoglycemia (p less than 0.05), macrosomia (p less than 0.05), and respiratory distress syndrome (p less than 0.01). One of six group I infants delivered at 35 to 36 weeks developed respiratory distress syndrome, compared with four of seven group II patients. The appearance of phosphatidylglycerol in amniotic fluid appeared delayed in group II patients at term. These data suggest that maintaining mean capillary blood glucose values less than 110 mg/dl may serve to reduce several major forms of morbidity in the infant of the diabetic mother. This information is helpful in establishing objectives for glycemic control in pregnant women using self-monitoring techniques.     

Is umbilical cord milking always an advantage?

Objective: The role of cord milking as an alternative to delayed cord clamping is an area that requires more research. Purpose of this clinical trial was to investigate the impact of umbilical cord milking on the absolute neutrophil counts (ANCs) and the neutropenia frequency of preterm infants.

Methods: Fifty-eight pregnant women were randomly assigned to one of the umbilical cord milking and control groups. A total of 54 preterm infants (gestational age ≤32 weeks) were enrolled into the study. The umbilical cords of 25 infants were clamped immediately after birth, and in 29 infants, umbilical cord milking was performed first.

Results: The ANCs were statistically significantly lower in the cord milking group compared with the control group on days 1, 3 and 7. The frequency of neutropenia was higher in the cord milking group compared with the control group.

Conclusion: In our study, ANCs were lower in the cord milking group and the frequency of neutropenia was higher. Umbilical cord milking plays a role on the ANCs of preterm infants.     

Timing of cord clamping revisited

Although cord cutting has been performed since the beginning of mankind, the timing and advantages of early versus delayed cord clamping are still controversial. Early cord clamping (within the first 30 s after birth) is usually justified for potential prevention of postpartum hemorrhage and for immediate treatment of the newborn, but at the same time, may increase Rh-sensitization. Delayed cord clamping is performed after a period of 30 s during which 'placental transfusion' of approximately 80 mL of blood occurs. This amount seems to protect the baby from childhood anemia without increasing hypervolemia-related risks. In preterm infants, delayed clamping appears to reduce the risk of intraventricular hemorrhage and the need for neonatal transfusion. Obtaining cord blood for future autologous transplantation of stem cells needs early clamping and seems to conflict with the infant's best interest. Although a tailored approach is required in the case of cord clamping, the balance of available data suggests that delayed cord clamping should be the method of choice.