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NCT Number: NCT06264973

Maternal and Fetal/Neonatal Pharmacokinetics and - Dynamics of Corticosteroids During Pregnancy

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.

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Key information

Conditions

Preterm Birth Female Urogenital Diseases and Pregnancy Complications Obstetric Labor Complications Obstetric Labor, Premature Pregnancy Complications Premature Birth Urogenital Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Older than 18 years of age.
  • 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.
  • Understanding of Dutch in speaking and reading.
  • Written informed consent.

In order for the neonate to be able to participate in this study, the parent must meet the following criteria:

  • Older than 18 years of age.
  • 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.
  • Understanding of Dutch in speaking and reading.
  • Written informed consent for the neonate.

Exclusion criteria

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

Treatment and study plan

Primary outcomes

  1. Pharmacokinetics of antenatal corticosteroids by investigation of betamethasone concentrations in serum using mmol/l

    Time frame: 2 days

    To examine the pharmacokinetics in maternal blood of standard regimen at the Erasmus MC of two doses of 12 mg betamethasone intramuscular with a 24 hours interval

Secondary outcomes

  1. Maternal age

    Time frame: 2 days

    To examine the relation between maternal age and the pharmacokinetics of the primary objective

  2. Fetal sex

    Time frame: 2 days

    To examine the relation between fetal sex and the pharmacokinetics of the primary objective

  3. Maternal weight/BMI in kg and kg/m2

    Time frame: 2 days

    To examine the relation between maternal weight/BMI and the pharmacokinetics of the primary objective

  4. Number of fetus

    Time frame: 2 days

    To examine the relation between the number of fetus and the pharmacokinetics of the primary objective

  5. Parity: the number of times a woman has given birth to a live neonate (any gestation) or at 24 weeks or more

    Time frame: 2 days

    To examine the relation between parity the pharmacokinetics of the primary objective

  6. PE by urine measurement of protein-creatinine ratio

    Time frame: 2 days

    To examine the relation between pre-eclampsia and the pharmacokinetics of the primary objective

  7. Oestradiol concentration in serum in mmol/l

    Time frame: 2 days

    To examine the relation between oestradiol on pharmacokinetics of the primary objective

  8. Cord blood and neonatal blood concentration in mmol/l of corticosteroids

    Time frame: Delivery

    To examine the relation between pharmacokinetics in cord blood and neonatal blood

Other outcomes

  1. CYP3A4 level

    Time frame: 2 days

    To examine the relation between CYP3A4 genotype and the pharmacokinetics of the primary objective

Study contacts

Contact information is provided by the study sponsor or research team.

Emma Ronde-Salminen, MD

CONTACT

[email protected]

0031683997312

Sam Schoenmakers, MD, PhD

CONTACT

[email protected]

0031107037439

Sponsors and collaborators

Lead sponsor

Erasmus Medical Center

Other

Registry information

Official study title

Maternal and Fetal/Neonatal Pharmacokinetics and - Dynamics of Corticosteroids During Pregnancy as Treatment for Fetal Lung Maturation MaDyCo-study

Acronym: MaDyCo

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Feb 20, 2024
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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