168 - 1 / 1 Delayed Cord Clamping and Fetal Hemoglobin in Extremely Preterm Infants During the First Two Weeks

Publication Number: 2162.168

Veronika Chytilova, Skane University Hospital, Hjärup, Skane Lan, Sweden; Sara Marie Larsson, Pediatrics, Department of Clinical Sciences Lund, Lund University/Department of Clinical Chemistry, Halland Hospitals, Sweden, Lund, Skane Lan, Sweden; Tommy Ulinder, 1. Institute of Clinical Sciences, Department of Pediatrics, Lund University, Lund, Sweden, Rydeback, Skane Lan, Sweden; Ann Knattan. Hellström, Neuroscience and Physiology, Hovås, Vastra Gotaland, Sweden; Ola Andersson, Lund University, Halmstad, Hallands Lan, Sweden; Margareta Gebka, Skånes University Hospital Lund, Lund, Skane Lan, Sweden; Linda Nilsson, Skåne University Hospital Lund, Lund, Skane Lan, Sweden; Karin Sävman, University of Gothenburg, Gothenburg, Vastra Gotaland, Sweden; Dirk Wackernagel, University of Mainz, Mainz, Rheinland-Pfalz, Germany; Mireille Vanpee, Karolinska Insitutet, Stockholm, Stockholms Lan, Sweden; Alexander Rakow, Karolinska University Hospital, Solna, Stockholms Lan, Sweden; Ingrid Hansen-Pupp, Lund University, Lund, Skane Lan, Sweden; David Ley, Lund University, Lund, Skane Lan, Sweden

Background: Postnatal decline in fetal hemoglobin (HbF) in extremely preterm infants is causally related to loss of endogenous fetal blood and replacement with adult donor blood. Low fractions of HbF have been associated with increased neonatal morbidities, including retinopathy of prematurity and bronchopulmonary dysplasia.

Objective: To investigate the association between cord clamping time (CCT) and HbF levels during the first two weeks of life in extremely preterm infants.

Design/Methods: This observational study was conducted as part of the LIM trial (NCT04239690), a prospective randomized multicenter intervention study aimed at minimizing blood loss using micromethods for clinical blood sampling. Infants < 27+0 weeks gestation were recruited from three Swedish NICUs between March 2020, and April 2024. Infants with registered CCT were assigned to two groups according to cord clamping time: early cord clamping group (ECC) < 60s and delayed cord clamping group (DCC) ≥ 60s. HbF% was measured from clinically indicated blood gas analyses and from chromatographic analysis.
Primary outcome was HbF% on day 1;7;14. Mixed-effects linear regression models were used to analyze repeated HbF% measures, adjusted for gestational age, birth weight, 1-minute Apgar score, study arm, and study site.

Results: A total of 139 infants with registered cord clamping time were included (ECC n=74; DCC n=65). Median CCT was 30 (10-30) s in the ECC group and 80 (60-100) s in the DCC group. Mean gestational age was 25.0 ± 1.2 weeks, with no significant group difference (p = 0.55). Overall, 56% were boys (ECC 49%, DCC 65%; p = 0.06).
In a mixed model, HbF% decreased significantly in both groups over the 14 days. Day 1, mean adjusted HbF% was comparable between the groups (DCC 92%, ECC 93%; p=0.7). On day 7, the DCC group had significantly higher HbF% than ECC (73% vs 65%, mean difference 8%, 95% CI 2-17; p=0.012). By day 14, HbF had further decreased with no significant difference between the groups (53% vs 51%, p=0.43). Figure 1 illustrates the decline in HbF% over time, with a slower reduction in the DCC group, during the first week of life.

Conclusion(s): Delayed cord clamping ≥ 60s in extremely preterm infants was associated with higher HbF% day 7. These findings suggest that delayed cord clamping may preserve HbF early in life. Ongoing analysis will assess whether DCC reduces transfusion requirements.

Adjusted HbF over time by cord clamping group
Adjusted mean fetal hemoglobin (HbF%) over the first 14 days of life by cord clamping group. Shaded areas represent 95% confidence intervals.