Late Vitamin K Deficiency-related Bleeding in Neonates (VKLB): Comparison of Different Strategies to Prophylaxis

NCT ID: NCT05713045

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-03-27
• Study Completion Date: 2023-01-20

Brief Summary

The goal of this multicentric observational study was to compare four vitamin K dosing regimens in exclusively breastfed healthy term newborns. The main questions it aims to answer were:

• comparing protein induced by vitamin K absence (PIVKA) levels in the different prophylaxis protocols at 48 hours, 1 month and 4 months
• to investigate the compliance and safety of oral vitamin K 1 administration Participants received vitamin K prophilaxis according to birth Hospital regimen. A blood sample was taken at 48 hours, 1 month and 3 months of life. Plasmatic PIVKA-II concentretion was be dosed

Researchers compared four groups of Vitamin K dosing regimens:

1. an intramuscolar injection of 1 mg vitamin K at birth

2. an intramuscolar injection of 1 mg vitamin K at birth followed by 50 μg/die orally from the second to the fourteenth week of life.

3. an intramuscolar injection of 1 mg vitamin K at birth followed by 150 μg/die orally from the second to the fourteenth week of life.

4. an oral dose of 2 mg vitamin K at birth, followed by a second dose at 4 weeks, and a third dose at 12 weeks to see if there is PIVKA-II plasmatic concentration differences.

Detailed Description

Partecipanting Centers

• Azienda Ospedaliera Universitaria di Parma
• Azienda Ospedaliera Universitaria di Siena
• Ospedale Buon Consiglio Fatebenefratelli, Napoli
• Ospedale Di Venere, Bari

Materials and Methods Term healthy newborn born from March 2019 to June 2021 was enrolled Vitamin K formulation was Konakion 2 mg/0,2 ml MM paediatric, solution for injection or oral administration, Cheplapharm Arzneimittel GMBH

PIVKA level was was measured on blood drops obtained by heel prick at 48 hours of life, 1 month and 3 months, using the PIVKA-II ELISA Kit, MyBiosource, San Diego, CA, USA.

Blood samples (0,5 ml) were collected in Lithium Heparine draw. After centrifugation at 1000 rpm for 15 minutes plasma was frozen and stored at -20°C. The samples were subsequently analyzed in the Laboratorio di Patologia Clinica, Università degli Studi di Siena.

Medication adherence was measured by questionnaires administrated to parents at 1 month and 3 months of life. A protocol violation (lack of vitamin K administration, concomitant use of other drugs except vitamins, ormula milk or mixed milk feeding) led to exclution of patients

Addictional collected data were:

• sex
• gestational age
• mode of delivery
• Apgar score
• antenatal corticosteroids
• antenatal antibiotics or others drugs
• birth weight
• premature rupture of membranes

Statistical analysis:

Statistical analysis was performed using SPSS 23.0 (IBM, Chicago, IL, USA) and MATLAB 8.0 (The MathWorks, Inc., Natick, MA, USA).

Data were tested for normality with the Shapiro-Wilk test, with the results expressed as mean and standard deviation, median and interquartile range, or frequency and percentage. Data were analyzed using Student's t-test or Wilcoxon rank-sum test for continuous data, and chi-square or Fisher's exact test for categorical variables. A two-tailed p-value <0.05 was considered significant. PIVKA levels were analyzed with repeated measures-ANOVA: different administration regimen was inserted as covariate.

Conditions

Late Vitamin K Deficiency-related Bleeding

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

intramuscolar injection

intramuscolar injection of 1 mg vitamin K at birth

Konakion

Intervention Type: DIETARY_SUPPLEMENT

Comparing 4 different regimen of Vitamin K administration in newborn

intramuscolar injection following by oral low dose

intramuscolar injection of 1 mg vitamin K at birth followed by 50 μg/die orally from the second to the fourteenth week of life

Konakion

Intervention Type: DIETARY_SUPPLEMENT

Comparing 4 different regimen of Vitamin K administration in newborn

intramuscolar injection following by oral high dose

intramuscolar injection of 1 mg vitamin K at birth followed by 150 μg/die orally from the second to the fourteenth week of life

Konakion

Intervention Type: DIETARY_SUPPLEMENT

Comparing 4 different regimen of Vitamin K administration in newborn

oral administration

oral dose of 2 mg vitamin K at birth, followed by a second dose at 4 weeks, and a third dose at 12 weeks

Konakion

Intervention Type: DIETARY_SUPPLEMENT

Comparing 4 different regimen of Vitamin K administration in newborn

Interventions

Konakion

Comparing 4 different regimen of Vitamin K administration in newborn

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• gestational age between 37+ 0/7 and 42+ 0/7 weeks
• exclusive breastfeeding
• Informed consent by at least one parent

Exclusion Criteria

• gestational age less than 37+ 0/7 weeks or more than 42+0/7 weeks
• neonatal disease
• liver disease
• formula milk or mixed milk feeding
• withdrawal of informed consent

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 1 Day
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliero-Universitaria di Parma

OTHER

Sponsor Role: lead

Responsible Party

Serafina Perrone

Director of Neonatology Unity, Department of Medicine and Surgery, University of Parma

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Pr Serafina Perrone

Parma, , Italy

Countries

Italy

References

Lembo C, Buonocore G, Perrone S. The challenge to define the optimal prophylactic regimen for vitamin K deficiency bleeding in infants. Acta Paediatr. 2021 Apr;110(4):1113-1118. doi: 10.1111/apa.15566. Epub 2020 Oct 6.

Reference Type: BACKGROUND

PMID: 32892390 (View on PubMed)

Shearer MJ. Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev. 2009 Mar;23(2):49-59. doi: 10.1016/j.blre.2008.06.001. Epub 2008 Sep 19.

Reference Type: BACKGROUND

PMID: 18804903 (View on PubMed)

American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003 Jul;112(1 Pt 1):191-2.

Reference Type: BACKGROUND

PMID: 12837888 (View on PubMed)

Mihatsch WA, Braegger C, Bronsky J, Campoy C, Domellof M, Fewtrell M, Mis NF, Hojsak I, Hulst J, Indrio F, Lapillonne A, Mlgaard C, Embleton N, van Goudoever J; ESPGHAN Committee on Nutrition. Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2016 Jul;63(1):123-9. doi: 10.1097/MPG.0000000000001232.

Reference Type: BACKGROUND

PMID: 27050049 (View on PubMed)

Other Identifiers

12150

Identifier Type: -

Identifier Source: org_study_id