Umbilical Cord Milking in Non-Vigorous Infants Didn’t Impact Neurodevelopment

NATIONAL HARBOR, Md. — Compared to early cord clamping (ECC), umbilical cord milking (UCM) in non-vigorous infants had short-term benefits without any long-term adverse impacts on neurodevelopment, according to the cluster-randomized crossover MINVI trial.

Among almost a thousand infants, those randomized to either UCM or ECC had comparable scores on the Ages and Stages Questionnaire, third edition (ASQ-3), as well as the Modified Checklist for Autism in Toddlers (M-CHAT-R), reported Anup Katheria, MD, director of the Neonatal Research Institute and the NICU follow-up clinic at Sharp Mary Birch Hospital for Women & Newborns and adjunct associate professor of pediatrics at the University of California San Diego.

The median ASQ-3 scores, which assessed communication, problem solving, fine motor, gross motor, and personal social skills, were 255 for both UCM and ECC (P=0.49). Medium-to-high M-CHAT-R scores were also similar at 9.3% for UCM and 8.4% for ECC (P=0.59), Katheria presented at the Society for Maternal-Fetal Medicine (SMFM) annual meeting.

The study is a long-term follow-up from a trial that compared UCM and early ECC in non-vigorous term and near-term newborns. The 10 hospitals in that study were cluster randomized to one of the interventions for 1 year. Last year, the preliminary results were presented at SMFM and published in the American Journal of Obstetrics and Gynecology. Katheria noted that the primary outcome — reduced neonatal intensive care unit (NICU) admissions — was not significantly reduced, though there was a trend for less NICU admissions for those randomized to UCM.

“But more importantly, for several of our pre-specified secondary outcomes, including the need for resuscitation in the delivery room, hemoglobin levels, moderate to severe HIV, the need for cooling, slightly higher peak bilirubin, and improved Apgar score at one minute were all better with umbilical cord milking versus early cord clamping,” Katheria said.

In the current study, rates of abnormal scores on the ASQ-3 subdomains were similar between groups:

• Communication: 11% for UCM vs 11% for ECC
• Gross motor: 7% vs 5%
• Fine motor: 5% vs 4%
• Problem solving: 6% vs 6%
• Personal-social: 9% vs 8%

On the M-CHAT-R, the majority of each group scored in the low-risk category (91% of UCM and 92% of ECC) with similar percentages scoring for medium risk (7% vs 7%) and high risk (2% vs 1%).

“Every single guideline in every country focuses on the vigorous term and pre-term babies, yet we have no guidelines for what to do for non-vigorous infants,” Katheria said. He noted that last month, the American Academy of Pediatrics (AAP) issued guidance that UCM may be reasonable for non-vigorous infants 35 to 42 weeks’ gestation. In 2021, the Resuscitation Council U.K. announced similar guidance.

Katheria concluded his presentation by posing the question of whether the American College of Obstetricians and Gynecologists (ACOG) would create guidance on this topic as well. Members of the audience wondered that, too.

David Hackney, MD, a maternal-fetal medicine doctor at Case Western Reserve University in Cleveland, told MedPage Today that in the past, there have been “some concerns and questions about whether or not [UCM] is safe because unlike delayed cord clamping, where you just wait before clamping the cord, you’re actively ‘milking’ the blood from the cord.”

Hackney also noted that obstetricians will likely be hesitant to change their practice until there are guidelines in place, but the results of Katheria’s study are promising.

The original trial included 1,730 newborns, of which 1,207 consented to long-term follow up. Average maternal age was 31 in both groups.

Researchers followed up with the child’s family to complete the ASQ-3 at 6, 12, and 22 to 26 months and the M-CHAT-R at 22 to 26 months. The team maintained contact with the families via text, phone, email, and written formats to enhance the follow-up rate. M-CHAT-R was used not to diagnose autism but rather because “it’s a very good screener for babies and children that will have early developmental disorders,” Katheria noted.

In total, four infants died in the hospital and three died post-discharge; 971 had ASQ-3 scores for analysis and 927 parents completed the M-CHAT-R. There were 502 in the UCM group and 469 in the ECC group. Whole hospitals were cluster randomized since randomizing individual babies would be too difficult.

Hospitals were trained to assess newborns within the first 15 seconds for poor color or tone and impaired respiration. If the newborn met any of those three criteria, they were included in the trial.

Katheria noted the study was limited by the lack of in-person examinations, the fact it was conducted in higher-income academic centers, that severe morbidities like severe hypoxic-ischemic encephalopathy and death were overall low, and that additional iron and stem cells received may have benefits that don’t present until early childhood.

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