Transfer of prednisolone into human breast milk and plasma of breastfeeding children - A low intervention cohort study with biobanking of breast milk and plasma (PREDBANK)

Study type

• Study type:
  Clinical trial

Clinical trials

• Clinical trial regulatory scope:
  Post-authorisation interventional clinical trial
• Clinical trial types:
  Low-intervention clinical trial

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (S01BA04) prednisolone

  prednisolone
• Medical condition to be studied:
  Rheumatoid arthritis

  Inflammatory bowel disease

  Systemic lupus erythematosus
• Additional medical condition(s):
  Myositis, psoriatric arthritis

Population studied

• Short description of the study population:
  Mothers with newborn infants 6-8 weeks postpartum
• Age groups:
  Adults (18 to < 46 years)
• Special population of interest:
  Nursing women
• Estimated number of subjects:
  30

Study design details

• Study design:
  Low interventional clinical trial
• Main study objective:
  The primary endpoint is the concentration of prednisolone in the breastfeeding child’s plasma 2h after feeding an infant breast milk, with the feeding taking place at 1h following maternal dose intake. ;
• Setting:
  Breast milk and blood will be collected merely to study excretion of prednisolone into breastmilk and transferal to her child. Participation in the trial will not decide or in any other way interfere with patients’ treatment as prescribed by their physician. Only patients that already have been assigned treatment with prednisolone by their physician and made the choice to breastfeed, will be approached and asked for participation. All procedures for blood collection will follow established routines at the clinical sites.; The sampling will take place ≈ 6-8 weeks after birth at the designated clinic. At this time point it is estimated that there is nothing left from medication taken during pregnancy.; Women willing to participate in the study will be provided with detailed information about what this entails and provided with a written informed consent form, that they will sign and also ask their partners (the other care giver) to sign. They will bring the signed informed consent form with them to the sampling center.; Breast milk will be collected once during the visit, using an electric breast milk pump. Venous blood will be collected from the woman and from the infant. After centrifugation, plasma samples and the breast milk sample will be shipped to Uppsala Biobank where it will be frozen and stored. Samples will be analysed for pharmacokinetic properties using mass spectrometry at the platform UDOPP, Department of Pharmacy, Uppsala University.
• Interventions:
  Blood sampling from infants
• Data analysis plan:
  Dosage of infant as Average Daily Infant Dose (ADID) in mg/kg/day will be estimated by using 200 mL/kg/day as a standard for daily milk intake in accordance with FDA guidelines for lactation studies (FDA Clinical Lactation Studies May 2019): “While a 150 mL/kg/day estimated milk intake is a reasonable assumption to estimate daily infant dosage, greater volumes do occur in early infancy and often correlate to the time of most reported infant adverse drug events. Additional consideration should be given to estimates of infant risk based on a 200 mL/kg/day milk intake in early infancy”.; Relative infant dose (RID) will be calculated by dividing infant dosage (ADID) in mg/kg/day with maternal dosage in mg/kg/day, multiplied with 100 in order to get the percentage. It is estimated that a RID < 10% is considered safe for the infant (Bennet PN, Use of the monographs on drugs, Drugs and Human Lactation, 1996:67-74.).; The maternal prednisolone/prednisone milk to plasma ratio will be calculated by dividing drug concentration in the mother’s milk with the drug concentration of the mother’s plasma.; Prednisolone concentration in infant blood will be reported. Cortisol concentration in infant blood will be reported.