Umbilical cord milking tied to severe IVH in very premature neonates

 

LAS VEGAS – Umbilical cord milking can cause severe intraventricular hemorrhage (IVH) in very premature neonates and should not be performed on these cerebrovascularly fragile premature babies.

Michele G. Sullivan/MDedge News

Just six of these procedures would be needed to cause a case of severe IVH in neonates born at 23-27 weeks’ gestation, Michael W. Varner, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Centers practicing umbilical cord milking should consider discontinuing this practice in infants 23-27 weeks’ gestation,” said Dr. Varner of the University of Utah, Salt Lake City.

The damage to the brains of very young preemies appears to be a direct result of the fluid overload caused by milking, he said. “From a mechanistic perspective, we can intuit that these findings are consistent with cord milking. This causes increasing venous return to the right atrium where it enters the foramen ovale and aorta. These very premature babies have more pulmonary vasoconstriction, which shunts more blood toward the brain. This results in fluctuations in flow in an immature brain with fragile germinal matrices and perhaps further compromised by chorioamnionitis inflammation, resulting in IVH.”

Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2) was a noninferiority trial of umbilical cord milking compared to delayed cord clamping and cutting in preterm infants. Conducted at 11 sites in the United States and Europe, the study was halted prematurely when the data safety monitoring board determined that cord milking increased the risk of IVH in younger preemies and was no better than delayed cutting in the older preemies. The analysis presented at the meeting is the first public discussion of the data details.

The trial involved 474 premature neonates. They were randomized to placental transfusion via a 60-second delay in cord clamping and cutting or to umbilical cord milking, which involved grasping the cord and manually pushing the cord blood toward the infant four times before clamping. All participating sites received a video demonstrating the proper procedure. The cohort also was divided by gestational age: 23-27 weeks and 28-31 weeks.

 

The primary endpoint was a combination of severe IVH (grade 3 or higher) and neonatal death. Overall, the primary endpoint occurred in 29 of those randomized to cord milking (12%) and 20 randomized to delayed clamping (8%) – a significant difference.

This finding was largely driven by the treatment differences in the 23-27 week group, Dr. Varner said. Severe IVH occurred in 20 (22%) of those randomized to cord milking and five (6%) of those randomized to delayed clamping – a highly statistically significant difference with a P value of 0.0019.

In the 28-31 week group, there were no cases of severe IVH in the cord milking group, and three cases in the delayed clamping group; the difference was not statistically significant.

Overall, deaths were similar between the cord milking and cord clamping groups (17 and 15, respectively). Most of these deaths occurred in the younger group (14 in the cord milking group and 13 in the clamping group). There were five deaths in the older group: three in the cord milking group and two in the clamping group. None of these differences were statistically significant.

After seeing these data in a preplanned interim safety analysis, the Data Safety Monitoring Board stopped the study, saying that the intervention appeared dangerous for the younger babies, and no better than the delayed cutting and clamping for the older group, Dr. Varner said.

Since the trial was halted, investigators have been dissecting the data to identify any other intracranial hemorrhage risks particular to the infants. They found no significant differences in maternal characteristics at baseline, and – other than age and randomization– nothing significantly different between the infant groups. Severe persistent IVH occurred in almost 70% of the infants born at 23 weeks’ gestation but in only 7% in the delayed cord clamping group. The risks declined rapidly with increasing gestational age, although they were at all times greater than the risk of IVH in the cord clamping group.

“Looking at the data by gestational age, it’s clear that the majority of the severe IVH occurrences were in the 23 weekers, and also occurred in the first 7 days of life,” Dr. Varner said.

The cohort will be followed for at least another year, he added, as investigators track neurodevelopmental outcomes.

Investigators are particularly interested in differences in motor and language skills, as well as general cognitive development.

The study was sponsored by theEunice Kennedy Shriver National Institute of Child Health and Development. Neither Dr. Varner nor any of the coauthors had any financial declarations.

SOURCE: Katheria AC et al. The Pregnancy Meeting, late breaking abstract 1.

 

LAS VEGAS – Umbilical cord milking can cause severe intraventricular hemorrhage (IVH) in very premature neonates and should not be performed on these cerebrovascularly fragile premature babies.

Michele G. Sullivan/MDedge News

Just six of these procedures would be needed to cause a case of severe IVH in neonates born at 23-27 weeks’ gestation, Michael W. Varner, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Centers practicing umbilical cord milking should consider discontinuing this practice in infants 23-27 weeks’ gestation,” said Dr. Varner of the University of Utah, Salt Lake City.

The damage to the brains of very young preemies appears to be a direct result of the fluid overload caused by milking, he said. “From a mechanistic perspective, we can intuit that these findings are consistent with cord milking. This causes increasing venous return to the right atrium where it enters the foramen ovale and aorta. These very premature babies have more pulmonary vasoconstriction, which shunts more blood toward the brain. This results in fluctuations in flow in an immature brain with fragile germinal matrices and perhaps further compromised by chorioamnionitis inflammation, resulting in IVH.”

Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2) was a noninferiority trial of umbilical cord milking compared to delayed cord clamping and cutting in preterm infants. Conducted at 11 sites in the United States and Europe, the study was halted prematurely when the data safety monitoring board determined that cord milking increased the risk of IVH in younger preemies and was no better than delayed cutting in the older preemies. The analysis presented at the meeting is the first public discussion of the data details.

The trial involved 474 premature neonates. They were randomized to placental transfusion via a 60-second delay in cord clamping and cutting or to umbilical cord milking, which involved grasping the cord and manually pushing the cord blood toward the infant four times before clamping. All participating sites received a video demonstrating the proper procedure. The cohort also was divided by gestational age: 23-27 weeks and 28-31 weeks.

 

The primary endpoint was a combination of severe IVH (grade 3 or higher) and neonatal death. Overall, the primary endpoint occurred in 29 of those randomized to cord milking (12%) and 20 randomized to delayed clamping (8%) – a significant difference.

This finding was largely driven by the treatment differences in the 23-27 week group, Dr. Varner said. Severe IVH occurred in 20 (22%) of those randomized to cord milking and five (6%) of those randomized to delayed clamping – a highly statistically significant difference with a P value of 0.0019.

In the 28-31 week group, there were no cases of severe IVH in the cord milking group, and three cases in the delayed clamping group; the difference was not statistically significant.

Overall, deaths were similar between the cord milking and cord clamping groups (17 and 15, respectively). Most of these deaths occurred in the younger group (14 in the cord milking group and 13 in the clamping group). There were five deaths in the older group: three in the cord milking group and two in the clamping group. None of these differences were statistically significant.

After seeing these data in a preplanned interim safety analysis, the Data Safety Monitoring Board stopped the study, saying that the intervention appeared dangerous for the younger babies, and no better than the delayed cutting and clamping for the older group, Dr. Varner said.

Since the trial was halted, investigators have been dissecting the data to identify any other intracranial hemorrhage risks particular to the infants. They found no significant differences in maternal characteristics at baseline, and – other than age and randomization– nothing significantly different between the infant groups. Severe persistent IVH occurred in almost 70% of the infants born at 23 weeks’ gestation but in only 7% in the delayed cord clamping group. The risks declined rapidly with increasing gestational age, although they were at all times greater than the risk of IVH in the cord clamping group.

“Looking at the data by gestational age, it’s clear that the majority of the severe IVH occurrences were in the 23 weekers, and also occurred in the first 7 days of life,” Dr. Varner said.

The cohort will be followed for at least another year, he added, as investigators track neurodevelopmental outcomes.

Investigators are particularly interested in differences in motor and language skills, as well as general cognitive development.

The study was sponsored by theEunice Kennedy Shriver National Institute of Child Health and Development. Neither Dr. Varner nor any of the coauthors had any financial declarations.

SOURCE: Katheria AC et al. The Pregnancy Meeting, late breaking abstract 1.

 

LAS VEGAS – Umbilical cord milking can cause severe intraventricular hemorrhage (IVH) in very premature neonates and should not be performed on these cerebrovascularly fragile premature babies.

Michele G. Sullivan/MDedge News

Just six of these procedures would be needed to cause a case of severe IVH in neonates born at 23-27 weeks’ gestation, Michael W. Varner, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Centers practicing umbilical cord milking should consider discontinuing this practice in infants 23-27 weeks’ gestation,” said Dr. Varner of the University of Utah, Salt Lake City.

The damage to the brains of very young preemies appears to be a direct result of the fluid overload caused by milking, he said. “From a mechanistic perspective, we can intuit that these findings are consistent with cord milking. This causes increasing venous return to the right atrium where it enters the foramen ovale and aorta. These very premature babies have more pulmonary vasoconstriction, which shunts more blood toward the brain. This results in fluctuations in flow in an immature brain with fragile germinal matrices and perhaps further compromised by chorioamnionitis inflammation, resulting in IVH.”

Premature Infants Receiving Milking or Delayed Cord Clamping (PREMOD2) was a noninferiority trial of umbilical cord milking compared to delayed cord clamping and cutting in preterm infants. Conducted at 11 sites in the United States and Europe, the study was halted prematurely when the data safety monitoring board determined that cord milking increased the risk of IVH in younger preemies and was no better than delayed cutting in the older preemies. The analysis presented at the meeting is the first public discussion of the data details.

The trial involved 474 premature neonates. They were randomized to placental transfusion via a 60-second delay in cord clamping and cutting or to umbilical cord milking, which involved grasping the cord and manually pushing the cord blood toward the infant four times before clamping. All participating sites received a video demonstrating the proper procedure. The cohort also was divided by gestational age: 23-27 weeks and 28-31 weeks.

 

The primary endpoint was a combination of severe IVH (grade 3 or higher) and neonatal death. Overall, the primary endpoint occurred in 29 of those randomized to cord milking (12%) and 20 randomized to delayed clamping (8%) – a significant difference.

This finding was largely driven by the treatment differences in the 23-27 week group, Dr. Varner said. Severe IVH occurred in 20 (22%) of those randomized to cord milking and five (6%) of those randomized to delayed clamping – a highly statistically significant difference with a P value of 0.0019.

In the 28-31 week group, there were no cases of severe IVH in the cord milking group, and three cases in the delayed clamping group; the difference was not statistically significant.

Overall, deaths were similar between the cord milking and cord clamping groups (17 and 15, respectively). Most of these deaths occurred in the younger group (14 in the cord milking group and 13 in the clamping group). There were five deaths in the older group: three in the cord milking group and two in the clamping group. None of these differences were statistically significant.

After seeing these data in a preplanned interim safety analysis, the Data Safety Monitoring Board stopped the study, saying that the intervention appeared dangerous for the younger babies, and no better than the delayed cutting and clamping for the older group, Dr. Varner said.

Since the trial was halted, investigators have been dissecting the data to identify any other intracranial hemorrhage risks particular to the infants. They found no significant differences in maternal characteristics at baseline, and – other than age and randomization– nothing significantly different between the infant groups. Severe persistent IVH occurred in almost 70% of the infants born at 23 weeks’ gestation but in only 7% in the delayed cord clamping group. The risks declined rapidly with increasing gestational age, although they were at all times greater than the risk of IVH in the cord clamping group.

“Looking at the data by gestational age, it’s clear that the majority of the severe IVH occurrences were in the 23 weekers, and also occurred in the first 7 days of life,” Dr. Varner said.

The cohort will be followed for at least another year, he added, as investigators track neurodevelopmental outcomes.

Investigators are particularly interested in differences in motor and language skills, as well as general cognitive development.

The study was sponsored by theEunice Kennedy Shriver National Institute of Child Health and Development. Neither Dr. Varner nor any of the coauthors had any financial declarations.

SOURCE: Katheria AC et al. The Pregnancy Meeting, late breaking abstract 1.