Betamethasone and Severity of Hyaline Membrane Disease

Study Overview
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Brief Summary
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Primary purpose: to study the relationship between betamethasone placental transfer and the occurrence and severity of the Hyaline Membrane Disease.

Detailed Description
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β-Mhyalines is a prospective multicentric non interventional study. One hundred fifty pregnant women at risk of premature delivery, in the framework of Hyaline Membrane Disease of the neonate, will receive 2 intramuscular injections of Celesten (betamethasone) at 24 hours interval. Plasma samples will be collected: 2 in the mother before delivery, one maternal and one cord samples at delivery. Concentrations will be measured and analyzed using a population approach. A ratio between neonatal and maternal exposure will be calculated to represent placental transfer. The effect of covariates (genetic polymorphism for CYP3A4, CYP3A5, P-glycoprotein…, and others variables as gestational age, bodyweight at birth, apgar score, co-medication, maternal disease) will be tested to explain the variability of placental transfer. The relationship between placental transfer and the occurrence and severity of the Hyaline Membrane Disease will then be study, in order to target betamethasone maternal concentration and thus to optimize the antenatal dose to administer to the mother in the framework of Hyaline Membrane Disease.

Official Title
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Betamethasone and Severity of Hyaline Membrane Disease in the Newborn Premature

Conditions
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Pregnant Women Receive Celesten

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women who received at least a first injection of Celesten in the prevention of MMH. A one-term> 27 SA, Major Patients > or = 18 years old Informed Consent Form signed Exclusion Criteria: Patients undergoing treatment with corticosteroids in the long term

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Celesten in prevention of hyaline membrane disease.<br>Pregnant women that received at least a first injection of Celesten in the prevention of hyaline membrane disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of neonates with hyaline membrane disease | respiratory symptoms (respiratory rhythm disorders, signs of retraction, cyanosis, oxgen dependance >30 %). Confirmation by radiology | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic polymorphisms | To study the pharmacogenetics of genetic polymorphisms that may affect the placental transfer of steroids (CYP-3A4, CYP-3A5, P-glycoprotein) | Day 1 | 
| mode of delivery | To study the variability of the factor  mode of delivery on fetal morbidity | Day 7 | 
| blood sample of betamethasone | To study the pharmacokinetics of betamethasone in all women treated | Day 1 and day 2 | 
| Optimal dose of betamethasone | Determine the optimal dose of betamethasone necessary for the prevention of MMH, especially in infants under 28 weeks | Day 28 | 
| gestational age | To study the variability of the factors gestational age on fetal morbidity | Day 7 | 
| birth weight | To study the variability of the factor  birth weight on fetal morbidity | Day 7 | 
| sex | To study the variability of the factor sex on fetal morbidity | Day 7 | 
| Apgar score | To study the variability of the factor  Apgar score  on fetal morbidity | Day 7 | 
| twinning | To study the variability of the factors twinning on fetal morbidity | Day 7 | 
| time between birth and the last dose | To study the variability of the factor time between birth and the last dose on fetal morbidity | Day 7 | 
| ethnicity | To study the variability of the factor ethnicity on fetal morbidity | Day 7 | 
| maternal disease and treatment | To study the variability of the factor  maternal disease and treatment on fetal morbidity | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyaline membrane disease, placenta, betamethasone