Clinical trial NCT06264973: Maternal and Fetal/Neonatal Pharmacokinetics and - Dynamics of Corticosteroids During Pregnancy
Official title: Maternal and Fetal/Neonatal Pharmacokinetics and - Dynamics of Corticosteroids During Pregnancy as Treatment for Fetal Lung Maturation MaDyCo-study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Preterm Birth
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pregnant women admitted at the Department of Obstetrics at Erasmus MC - Sophia for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks. Postpartum, the neonates will also be included in the study.

Brief summary: Improving pregnancy outcome is essential in improving health of both parents and their offspring during the life course. Preterm birth (PTB) occurs in 10-15% of all pregnancies, is the leading cause of perinatal mortality and morbidity {Goldenberg, 2008}, has long-term adverse consequences for postnatal health {Huddy, 2001} and is a burden for health care expenditure. In order to improve neonatal outcome, antenatal corticosteroids (ACS) are routinely administered to women at risk for preterm delivery before 34 weeks of pregnancy. {Jobe, 2018;Roberts, 2017;Travers, 2018} However, the current, worldwide standard of care, for the use of ACS is still based on animal experiments performed in the 1970's. {Liggins, 1969} Although ACS treatment to improve neonatal outcome was clinically introduced in the 70's, still only two dosing regimens are used, neither of which have been investigated, re-evaluated or refined to determine the optimal doses or treatment interval. With the current health care approach of personalized medicine in mind, the same universal approach for everybody, independent of gestational age, number of fetus, maternal weight or comorbidity one dose does not fit all since it often has not the desired effect. Due to the lack of optimization of the above mentioned synthetic corticosteroid drug regimens {Kemp, 2019}, significant gaps in knowledge exist. An important aspect to set up, investigate and understand dosing and also dosing interval experiments, is knowledge of the maternal individual pharmacokinetics and pharmacogenetics of the drug of interest during pregnancy.

Detailed description: A clinical observational study will be performed in women admitted at the Department of Obstetrics at the Sophia Children's Hospital/Erasmus MC for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks. Antenatal corticosteroids will be administered according to the local standard protocol (12 mg betamethasone intramuscular with a 24 hours intervall). Importantly, clinical management of women with suspicion of preterm birth will not be affected by the proposed study. After inclusion, repetitive blood sampling according to the following schedule: t0 (administration), t0-30 min, t10-12hrs and t20-24 hrs. Umbilical cord will be sampled directly after birth as fetal determinant in which corticosteroids and their metabolites will be measured. Also, neonatal blood samples (drawn by the paediatricians as part of standard care) will be used for measurement of corticosteroids and their metabolites. Maternal blood samples will furthermore be analysed for determinants effecting pharmacokinetics such as oestradiol.

Eligibility criteria: Inclusion Criteria:

1. Older than 18 years of age.
2. Admitted at the Department of Obstetrics at Erasmus MC - Sophia for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks.
3. Understanding of Dutch in speaking and reading.
4. Written informed consent.

   In order for the neonate to be able to participate in this study, the parent must meet the following criteria:
5. Older than 18 years of age.
6. Admitted at the Department of Obstetrics at Erasmus MC - Sophia for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks.
7. Understanding of Dutch in speaking and reading.
8. Written informed consent for the neonate.

Exclusion Criteria:

1. Women unable or unwilling to agree with the procedures.
2. Women unable or unwilling to give written informed consent.
3. Women with acute obstetric complications requiring immediate delivery at time of admission.

Primary outcomes:
measure: Pharmacokinetics of antenatal corticosteroids by investigation of betamethasone concentrations in serum using mmol/l
timeFrame: 2 days
Secondary outcomes:
measure: Maternal age
timeFrame: 2 days
measure: Fetal sex
timeFrame: 2 days
measure: Maternal weight/BMI in kg and kg/m2
timeFrame: 2 days
measure: Number of fetus
timeFrame: 2 days
measure: Parity: the number of times a woman has given birth to a live neonate (any gestation) or at 24 weeks or more
timeFrame: 2 days
measure: PE by urine measurement of protein-creatinine ratio
timeFrame: 2 days
measure: Oestradiol concentration in serum in mmol/l
timeFrame: 2 days
measure: Cord blood and neonatal blood concentration in mmol/l of corticosteroids
timeFrame: Delivery
Other outcomes:
measure: CYP3A4 level
timeFrame: 2 days
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid Holland
Study officials:
affiliation: Erasmus Medical Center
name: Sam Schoenmakers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: