delayed cord clamping

Current recommendations by the American College of Obstetrician and Gyne- cologists (ACOG) encourage the use of delayed umbilical cord clamping (DCC) in all premature neonates as a means of placental transfusion because of its sig- nificant associated benefits [1]. Despite substantial evidence that placental transfusion by delayed cord clamping improves transitional circulation, de- creases the need for blood transfusion, and lowers the incidence of necrotizing enterocolitis (NEC) and intraventricular hemorrhage (IVH) in preterm neo- nates, there appears to be reluctance to adopt DCC. This may be due to concern about delayed neonatal resuscitation until the cord is clamped and cut [2]. To avoid this delay, the study of two distinct approaches to immediate resuscitation efforts that preserve placental transfusion was examined. One such effort is the use of the mobile trolley to initiate resuscitation at the mother’s bedside. Mobile trolley resuscitation has been shown to be a safe and successful way to delay cord clamping in applicable settings [3] but significant planning and resources must be devoted to the installation and use of a trolley. Alternatively, the stripping of blood from the umbilical cord, or umbilical cord milking (UCM) as a means of placental transfusion has been hypothesized as a fast and effective way to pro- vide the benefits of placental transfusion to the neonate [4].

A limitation of our study is that we did not obtain a comparison group of infants receiving early or immedi- ate cord clamping, since the aim of our study was to de- termine the infant’s physiological changes occurring during delayed cord clamping. In our center delayed cord clamping is practiced by the majority of our obste- tricians and often requested by parents. We did not feel it would be ethical to randomize newborns to receive a treatment that would change our accepted practice or be against parental wishes. In addition we did not obtain weights of the infants to compare the amount of placen- tal transfusion. Lastly to limit the amount of monitoring during the bonding period we also did not continue monitoring past 5 minutes. We believe this study pro- vides pilot important information and future studies will build on our data to determine the normal range of hemodynamics of the neonate immediately after birth.

Index (RI), Pulsatility Index (PI) and cerebral blood flow velocities of middle cerebral artery (MCA) were measured at 24 to 48h of life. A recent meta-analysis of UCM including seven randomized clinical trials involving 501 infants delivered at < 33 weeks, demonstrated that infants who underwent UCM had a higher hemoglobin level and lower risk of oxygen requirement at 36 weeks and IVH of all grades compared with those who underwent immediate cord clamping. Our results were consistent with this study. In present study we demonstrated that in both pre-term and early term neonates, the hematological and hemodynamic effects of umbilical cord milking (UCM) were similar to those of delayed cord clamping (DCC) after 60-90 seconds of birth. 10

In the United States, the practice of DCC in preterm newborns has not been widely adopted and few institutions have policies regarding DCC [11]. A myriad of barriers exist that may hinder adoption of DCC. Uncertainties sur- rounding DCC need to be addressed when considering implementing this practice. For provider’ s accustomed to ICC, the recommended 30 to 60 second range to perform DCC in preterm infants [4] may be perceived as non- specific and may raise concerns that inconsistent DCC practices could lead to variable outcomes. However, evidence-based guidelines are often collectively derived from studies that used non-standardized parameters, which leads to recommended ranges, exemplified in the Neonatal Resuscitation Program (NRP) with endotracheal tube epi- nephrine (1:10,000 concentration; 0.1 mg/ml) dose ranges from 0.5 – 1 ml/kg that can be repeated every 3 – 5 minutes [12]. Another barrier preventing endorsement of DCC may be provider perceptions of potential harm associated with DCC that may be incongruent with existing evidence refuting these concerns (e.g., the assumption that maternal hemorrhage is reduced with ICC when no difference has been demonstrated in multiple studies) [13]. A lack of awareness of potential infant benefits beyond placental neo- natal transfusion, such as an almost 50% reduction in intra- ventricular hemorrhage all grades (10 trials, 539 infants, RR 0.59, CI 0.41-0.85, NNT 15) [2], may limit enthusiasm to- ward DCC. In addition, the term “delayed” cord clamping may also contribute to hesitancy in adopting DCC, since this term is often associated with a negative con- notation of waiting, particularly in a society that values immediate service, instant access, and quick results.

The circulatory system of a newborn undergoes drastic transitions to adapt to the ex utero life, during which respiratory function is transferred from placenta to lungs. A smooth and event free transition is important for infant’s well-being and constitutes grounds for a healthy pediatric development. Although being very common, it is recommended to avoid immediate cord clamping (ICC) as its harmful effects for neonates are being documented in recent bodies of work [1, 2]. Our recent work elucidated the role of hemodynamics in cir- culatory transition from fetal-to-neonatal life in “term” neonates [3]. An abrupt removal of the placental circula- tion via ICC resulted in a lower cardiac output, a lower organ blood flow mediated by a decreased cardiac pre- load related to hypovolemia, and neonatal hypoxia when the cord is clamped before ventilation is established [4]. These quantitative findings are supported by the clinical studies performed during or immediately after birth in which delayed cord clamping (DCC) was found to be improving the early oxygenation [5], cardiac output [6], blood volume [7], in human neonates, and hemodynamic stability in fetal lamb studies [8] com- pared with ICC. Consequently, it has been observed that DCC has a lower incidence of bradycardia [8], iron defi- ciency [9] and provides an increased hematocrit [10] of the neonate during the early developmental phase. A re- ported adverse neonatal effect of DCC in term babies by The American College of Obstetricians and Gynecolo- gists Committee is increase of jaundice requiring photo- therapy, without any adverse maternal effect [11]. On the other hand, while systematic reviews of randomized controlled trials in babies born claimed DCC reduced the incidence of intraventricular hemorrhage [6, 10], more recent ones including meta-analysis concluded that effect of DCC on reducing all grades of intraventric- ular hemorrhage is no longer significant [12, 13].

estimate that a new-born infant requires approximately 0.7 mg of iron per day for growth and development, maintenance of hemoglobin levels and myoglobin and enzyme levels in muscle and other tissues, 46-60 mg would be equivalent to roughly 1-3 months of infant iron requirements. Likewise, immediately clamping the umbilical cord will deprive the infant of a substantial portion of TBI at birth. In preterm neonates, this measure of extra iron would make significant differences to growth during infancy. Thus, the purpose of this study was to testify that umbilical cord milking is an efficient placental transfusion strategy over delayed cord clamping to improve iron status among the preterm neonates as shown by higher ferritin levels at 6 weeks of life.

Deliveries were managed as per the institutional protocol. Group A (early cord clamping) had patients where cord clamping was done within 30 seconds and in Group B (delayed cord clamping) cord was clamped after 60 seconds. Inj oxytocin 10 mg was used as prophylactic uterotonic for all patients at the time of delivery. Patients showing evidence of acute intrapartum fetal distress were excluded. Immediate neonatal resuscitation was carried out and babies were roomed in with mother. Any baby admitted to NICU after delivery (other than for short period of observation) was excluded from the study except those developing transient tachypnea of new-born. Mothers were observed for 1 hour after delivery for evidence of atonic PPH (≥500 ml for vaginal delivery and ≥1000 ml for caesarean delivery). 72 hours after delivery neonatal blood for haemoglobin, haematocrit and serum bilirubin estimation was sent. The mothers and the newborns were evaluated with reference to neonatal haemoglobin, haematocrit and neonatal or maternal complications if any. Data was entered in excel sheet, the results were tabulated and statistically analysed by statistical package SPSS17.

This is to certify that the dissertation entitled “COMPARISON OF DELAYED CORD CLAMPING AND UMBILICAL CORD MILKING IN LATE PRETERM AND TERM INFANTS – AN OPEN LABEL RANDOMISED CONTROL TRIAL” is a bonafide work done by Dr.S.BALAJI under my guidance and supervision during the period between Nov 2013 – Feb 2014 towards the partial fulfilment of requirement for the award of D.M. (Neonatology) degree examination to be held in August 2014 by the Tamilnadu Dr. M.G.R. Medical University, Chennai.

The proportion of infants with iron deficiency at 3 months of age in our study was lower in DCC group although hemoglobin levels were similar. We did not observe differ- ence in hemoglobin probably because iron deficiency pro- gresses in stages with erythropoiesis affected only after bone marrow iron stores and serum ferritin levels have decreased considerably [23]. A longer follow up might have possibly detected the difference in hemoglobin levels. A recent Cochrane review comparing early and delayed cord clamping strategies in term infants has also shown similar results of lower incidence of iron deficiency in DCC group and similar hemoglobin in both the groups [6].

Despite the above limitations, our findings suggest that cord clamping can be safely delayed for at least 120 s in elective CD without resulting in excess maternal blood loss and further suggest maternal blood loss may be decreased with the protocol utilized. Given the potential benefit of improved iron status on infant neurodevelop- mental outcomes and the dearth of data available in this country regarding infant iron status and related out- comes, these results call for a larger, randomized trial of DCC in elective CD evaluating both short- and longer- term outcomes for both members of the dyad. The need for such a trial is particularly compelling with the recent report that delayed cord clamping in Sweden, a high- income country, reduced the number of children with low fine-motor and social skill scores at 4 years of age [26]. An editorial in the same JAMA issue highlighted that since 2000, no randomized trial has documented symptomatic polycythemia in infants [27]. Intuitively, there is reason to think newborn outcomes related to DCC are likely similar to those in vaginal deliveries, but this needs to be confirmed prior to recommending its use. Lastly, it will be important to confirm if this 120 s delay can also improve outcomes for the mother, an in- triguing possibility which is suggested by our and other data.

The observational study in newborns by Smith et al. Two thousand fourteen also showed early clamping resulted in a higher heart rate [16]. Findings of Polglase et al. and Smith et al. was concurrent with our findings on higher oxygen saturation and lower heart rate in the first 5 min of birth in the DCC group [16, 21]. Katheria et al. conducted a feasibility trial on measuring cardiac changes during delayed cord clamping after vaginal de- livery in term infant. Cardiac output increased from 2 to 5 min of birth [22].

This is the first study to compare developmental outcomes in babies born very preterm who either experience cord milking or delayed cord clamping at birth. It is also the longest follow-up of infants involved in a placental transfusion trial. A previous study comparing immediate and delayed cord clamping followed infants up to seven months of age but the authors recommended that follow-up should be at approximately four years as this is when motor outcomes stabilise. 5 However, the sample sizes at both time points in our trial were relatively small, and the pilot trial was

outcome at term. This was a randomized, controlled trial performed in 2 obstetrical units in Argentina on neonates born at term without complications to mothers with uneventful pregnancies. After written parental consents were obtained, newborns were randomly assigned to cord clamping within the first 15 seconds (group 1), at 1 minute (group 2), or at 3 minutes (group 3) after birth. The infants’ venous haematocrit value was measured 6 hours after birth. Two hundred seventy-six newborns were recruited. Mean venous haematocrit values at 6 hours of life were 53.5% (group 1), 57.0% (group 2), and 59.4% (group 3). The result of the study showed that delayed cord clamping at birth increases neonatal mean venous haematocrit within a physiologic range. No harmful effects were observed among groups. Furthermore, this intervention seemed to reduce the rate of anemia.

neonates. 9,15-20 A randomized study by Purisch et al, 21 com- pared immediate cord clamping (within 15 seconds after birth) with DCC (60 seconds after birth) in cesarean delivery. This study demonstrated that mean neonatal hemoglobin level was higher in the DCC group (18.1 g/dl vs 16.4 g/dl). However, the recommended timing of DCC in cesarean delivery is still problematic. Delayed cord clamping time in vaginal delivery can vary between 30 seconds, to more than 1 minute, or as long as the mother request but there is no de fi nite DCC time recommended in cesarean delivery. 4,8,10

A total of 150 pairs of healthy mothers and their neonates were enrolled in the study and 50 pairs were excluded from the study because 20 of them didn’t meet inclusion criteria, 20 pairs refuse to participate and 10 pairs withdraw before completion of assessment. The remaining 100 pairs were assigned into 2 groups: – Early cord clamping (ECC) group and delayed cord clamping (DCC) group based on computer-generated random numbers. The obstetrician conducting the delivery was informed the group allocation prior to the delivery. In the ECC group, the umbilical cord was clamped within 30 s of fetus expulsion and in the DCC, the umbilical cord was left at 20 cm below the vaginal introitus and then clamped at 2 min after expulsion. The selection of a 2-min interval was based on WHO 2012 recommenda- tions for clamping of the cord [3]. Newborn infants in the DCC were held in their mothers’ arms while waiting for the cord to be clamped.

*The ICC group was defined as a reference; **Mean or median differences and 95% confidence intervals from multivariable linear or quantile regression models adjusted for birth weight, gestational age, weight loss (0–7%, 7.1–10%, and >10%), and type of feeding (exclusive breastfeeding, mixed, and bottle); mean ± standard deviation for normally distributed data; median (IQR) for not normally distributed data; CB, Capillary Bilirubin; CI, Confidence Interval; DCC, Delayed Cord Clamping; dl, deciliter; ICC, Immediate Cord Clamping; IQR, InterQuartile Range; mg, milligrams; NS, Newborn Screening; SD, Standard Deviation.

In a perinatal centre located in a community hospital in Denver, the implementation of DCC for premature infants with GA <35 weeks was very successful, increasing from 19.5% in 2013 to 85% in 2017. This successful imple- mentation of an evidence-based guideline was achieved, thanks to a progressive engagement, feedback and educa- tion of key stakeholders. In our case we believe that the Figure 2 Delayed cord clamping performance and PDSAs. The frequency of delayed cord clamping for at least 60 s (blue line) is shown by quarterly performance in this control chart. It increased from 19.5% in 2013 (baseline observation) to 85% after the third quarter of 2015. The initiation of the implementation of the four PDSA cycles is demonstrated by the respective coloured arrows. CL, control limit; CPG, clinical practice guideline; DCC, delayed cord clamping; LCL, lower control limit; UCL, upper control limit; PDSA, plan, do, study, act. 

had their cord clamped after a mean of 172 s compared with a control group who had their cord clamped after a mean of 28 s had higher haematocrit at 48 hours, as well as higher ferritin and evidence of better myelin- ation of the internal capsule and other areas of the brain essential to visual, motor and sensory function/integra- tion at 4 months of age. 7 Term infants randomised to

The written informed consent from the eligible pregnant women before delivery was obtained. The pregnant women who delivered only at Ramathibodi Hospital were enrolled. The inclusion criteria were living singleton term pregnan- cies (37 – 42 weeks of gestation). The exclusion criteria were umbilical cord length less than 25 cm or cord abnormality (such as true knots or cord prolapse), multiple gestation, maternal Rh-negative blood group, positive anti-HIV, posi- tive HBsAg, and syphilis infection during pregnancy, antenatal diagnosed major congenital anomalies of fetus or apparent at birth, fetal hydrops and fetal growth restric- tion, intrapartum fetal nonreassuring or fetal distress, non-vigorous neonates, unstable maternal hemodynamic condition, placenta abruption, placenta previa, uterine rup- ture and denied to participate.

Gestational age and Hb at first IUT were comparable (Table 2). Antenatal management was similar during the periods with comparable delay between last IUT and birth, and same rate of MCA PSV ≥ 1.5 MoM before delivery. We observed 5 emergency cesarean deliveries (4 in ICC group and 1 in DCC group) secondary to bradychardia during the IUT. Cord clamping was done before resuscitation by the pediatrician.