Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth

Clarke, Paul ORCID: https://orcid.org/0000-0001-6203-7632, Shearer, Martin J., Card, David J., Nichols, Amy, Ponnusamy, Vennila, Mahaveer, Ajit, Voong, Kieran, Dockery, Karen, Holland, Nicky, Mulla, Shaveta, Hall, Lindsay J. ORCID: https://orcid.org/0000-0001-8938-5709, Maassen, Cecile, Lux, Petra, Schurgers, Leon J. and Harrington, Dominic J. (2022) Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth. Journal of Thrombosis and Haemostasis, 20 (12). pp. 2773-2785. ISSN 1538-7933

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Abstract

Background: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. Objectives: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla-proteins, factor II (PIVKA-II) and osteocalcin (GluOC), synthesized by liver and bone respectively. Patients/Methods: Prospective, multi-center, observational study in preterm infants born <33 weeks’ gestation. Blood samples and dietary history were collected before hospital discharge, and post discharge at 2-3 months corrected age. Outcome measures were serum VK1, PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants post-discharge. Results: Post discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA-II (0.10 vs. 0.02 AU/mL) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only 1 (2%) of 45 breastmilk-fed infants was VK insufficient. Post-discharge, 8 (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only 1 (4%) of 25 formula/mixed-fed babies. Conclusions: Preterm infants who remain exclusively or predominantly human breastmilk-fed post neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine post-discharge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.

Item Type:	Article
Additional Information:	Research Funding: P.C. and S.M. received support to conduct this research from their institution (NNUH) via NIHR Research Capability Funding awards. P.C. also received support from the NNUH Charitable Fund and UEA Medical School.
Uncontrolled Keywords:	hemorrhage,infant,nutrition,vitamin k deficiency,vitamin k1,hematology ,/dk/atira/pure/subjectarea/asjc/2700/2720
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Medicine and Health Sciences > School of Health Sciences
Related URLs:	http://www.scopus.com/inward/record.url?... https://onlinelibrary.wiley.com/doi/epdf...
Depositing User:	LivePure Connector
Date Deposited:	21 Sep 2022 17:30
Last Modified:	14 Nov 2022 12:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/88571
DOI:	10.1111/jth.15874

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