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

Azienda Ospedaliero-Universitaria di Parma

Status: Completed

Conditions: Late Vitamin K Deficiency-related Bleeding

Treatments: Dietary Supplement: Konakion

Study type: Observational

Funder types: Other

Identifiers

NCT05713045

12150

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: All

Ages: 1 to 1 day old

Volunteers: No Healthy Volunteers

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

Trial design

80 participants in 4 patient groups

intramuscolar injection

Description:

intramuscolar injection of 1 mg vitamin K at birth

Treatment:

Dietary Supplement: Konakion

intramuscolar injection following by oral low dose

Description:

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

Treatment:

Dietary Supplement: Konakion

intramuscolar injection following by oral high dose

Description:

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

Treatment:

Dietary Supplement: Konakion

oral administration

Description:

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

Treatment:

Dietary Supplement: Konakion