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There was no difference in maternal blood loss for women with scheduled cesarean delivery when comparing delayed clamping of the umbilical cord to immediate clamping, a randomized trial found.

Mean hemoglobin change was non-significant between the immediate and delayed cord clamping groups, reported Cynthia Gyamfi-Bannerman, MD, of Columbia University Irving Medical Center in New York City, and colleagues, writing in .

The authors noted prior research that found delayed cord clamping was associated with health benefits for the infant, from improved neonatal hemoglobin levels in the first few days of life to improvements in iron stores at age 3 to 6 months to even improved neurodevelopmental performance through age 4. Given these benefits, the researchers noted, the American College of Obstetricians and Gynecologists recommended delayed umbilical cord clamping for at least 30 to 60 seconds after birth, regardless of mode of delivery.

However, there are limited data about maternal outcomes -- specifically for women delivering via cesarean -- where the investigators explained that "the mean blood loss is at least twice that of a vaginal delivery with the potential for increased bleeding from delayed hysterotomy closure."

Study Details

The team randomized women at two hospitals in New York City who were undergoing scheduled cesarean deliveries of term pregnancies (defined as at least 37 weeks gestation) -- 56 to immediate (15 seconds after birth) and 57 to delayed cord clamping (at least 60 seconds after birth). The primary outcome was change in maternal hemoglobin from preoperative levels to postoperative day 1 levels.

Patients were a median age 39, and of patients who reported their race, about 56% to 65% were white. These women had a low rate of prior postpartum hemorrhage (4.4%), and all deliveries were performed under neuraxial anesthesia. Median time to cord clamping was 63 seconds in the delayed group versus 6 seconds in the immediate group, although the authors noted that three women in the delayed group had cord clamping performed prior to 60 seconds -- two for neonatal resuscitation after difficult deliveries and one for concern about maternal bleeding.

Mean hemoglobin level at postoperative day 1 was 10.1 g/dL in the delayed group and 9.8 g/dL in the immediate group. Compared with preoperative hemoglobin levels, there was a mean decrease of -1.90 g/dL in the delayed group compared with -1.78 g/dL in the immediate group.

There were no differences in maternal secondary outcomes, but the authors found that of available neonates, the mean neonatal hemoglobin level was significantly higher in the delayed group compared with the immediate group (18.1 g/dL vs 16.4 dL, mean difference of 1.67 g/dL, P<0.001).

The authors reported that there was one unplanned hysterectomy in each group, but no maternal ICU admissions, and at 30 days postpartum, "additional complications were rare."

Signal of Harm in Umbilical Cord Milking in Preterm Infants

A , also published in JAMA, found that while there was no significant difference in a composite outcome of death and severe intraventricular hemorrhage in preterm infants with umbilical cord "milking" compared with delayed umbilical cord clamping, the rate of severe intraventricular hemorrhage alone was significantly higher in the milking group.

A post hoc analysis of a previously stopped randomized trial found no significant difference in the composite rate of both outcomes between groups (12% in the milking group vs 8% in the clamping group, risk difference 4%, P=0.16), but there was a significant difference in the risk of severe intraventricular hemorrhage among preterm infants (8% in the milking group vs 3% in the clamping group, P=0.02), reported Anup Katheria, MD, of Sharp Mary Birch Hospital for Women & Newborns in San Diego, and colleagues.

This was originally supposed to be a multicenter non-inferiority randomized trial in four countries, but the authors noted a safety signal suggesting an imbalance in severe intraventricular hemorrhage between groups when the first interim analysis was performed, and the trial was immediately stopped. Participants were infants born at less than 32 weeks gestation.

Delayed cord clamping was at least 60 seconds after delivery, while umbilical cord milking was done for approximately 2 seconds, allowing refill, and then repeated three more times, the researchers said.

Thus, this was a post hoc analysis of the 474 infants that had enrolled and completed the trial. Infants were a mean gestational age of 28 weeks and 46% were girls.

The authors also noted that a test for interaction between gestational age and treatment group was not significant for the composite outcome, but was significant for severe intraventricular hemorrhage -- with a significantly higher rate among the milking group versus the clamping group at 22 to 27 weeks gestation (22% vs 6%, respectively, P=0.002).

Writing in an , Heike Rabe, MD, of the University of Sussex in Brighton, U.K., and Ola Andersson, PhD, of Lund University in Sweden, noted that the World Health Organization also recommends delayed cord clamping and cutting for at least 60 seconds for preterm infants and 1 to 3 minutes for term infants "to allow placental transfusion to take place."

Rabe and Andersson appeared to take issue with the results of the study, noting that "umbilical cord milking has been used in many hospitals without an increase in intraventricular hemorrhage being observed."

However, the editorialists added, given these results and the signal of harm reported, "further studies of umbilical cord milking should only be conducted once the results of the ongoing trials are reported, especially for infants at 23 to 27 weeks' gestational age."

Rabe and Andersson also suggested that standardized best practices are needed for preterm infants, not only in terms of cord milking versus cord clamping, but in regards to "the duration of delay, the positioning of the infant with regard to the placenta, the number of times the intact cord should be milked, and the use of uterotonics."