Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth restricted neonates: A randomized controlled trial

Aim: To evaluate the effects of umbilical cord milking (UCM) on systemic blood flow in comparison with delayed cord clamping (DCC) in intrauterine growth restricted (IUGR) neonates.

 Subjects: Antenatally diagnosed IUGR neonates of ≥28 weeks’ gestation consecutively delivered in AIIMS, Rishikesh will be assessed for eligibility.

Fetal weight as measured by ultrasonography in second half of pregnancy will be plotted on Intergrowth 21st chart. Pregnancy with fetal weight < 10th centile would be considered eligible for the study after obtaining a written informed consent from either parent.

 Intervention: NICU and delivery unit team would be trained in the study procedure before the trial is started. In all cases after birth, the neonates will be placed on the mother’s abdomen in case of vaginal delivery and on the thighs in case of Caesarean delivery before clamping the cord. The intervention in the UCM group will include gentle grasping of the uncut umbilical cord and squeezing approximately 20 cm of the cord at the speed of 10cm/sec towards the infant for four times. A short waiting time of 2 seconds in between two squeezing movements will be ensured for quick refilling the cord.

 In DCC group the delivering obstetrician will position the baby as previously described and delay clamping for at least 60 seconds while the baby will be placed in warm, sterile towel and given gentle stimulation. Neonatal care would be provided according to standard practice at the hospital. SVC blood flow and RVO will be determined by echocardiography.

Anterior cerebral artery and superior mesenteric artery blood flow will be studied by ultrasound and color Doppler. Cerebral regional oxygen saturation (rScO2) will be measured by near infra-red spectrometry. Mean blood pressure and perfusion index will be documented. Blood samples for hematocrit will be drawn from a peripheral vein under aseptic precautions. Study neonates will be managed as per our unit protocol.

Sample Size: As there is lack of data comparing UCM and DCC exclusively in IUGR infants, sample size is calculated with reference to a previous study in preterm neonates. The study found a mean SVC flow of 93 mL/kg/min with standard deviation (SD) of 24 at 12 hours of life in UCM group and mean of 81 mL/kg/min with SD of 29 in DCC group.

Expecting a similar difference in SVC flow, considering a power of the study as 80% and 2 tailed alpha error as 0.05, a total sample size of 156 was calculated (78 in each group).  Anticipating a dropout rate of 10%, final sample size was calculated to be 172 (86) in each group.

Statistical analysis: All the data will be uploaded into the excel sheet (Microsoft excel 2016). Analysis of data will be done by using SPSS software version 21. Continuous variables with normal distribution will be presented as mean ± SD. Categorical variables will be presented as proportions. Quantitative data with normal distribution will be compared using Student T test and those with skewed distribution will be analyzed using Mann Whitney U test. Data expressed as proportions will be compared using Chi square or Fisher exact test as applicable. Mean and 95% confidence interval will be calculated for outcome variables. Subgroup analysis will be done as per stratifications with analysis of variance (ANOVA) test. A p-value of <0.05 will be considered statistically significant.