Effect of Steroid Administration on Maternal Blood Levels of hLPCAT1 mRNA

Study Overview
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Brief Summary
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Neonatal respiratory distress syndrome affects babies who are born preterm and requires them to be placed on a ventilator in the Intensive Care Unit. Over 15 million babies were born premature and these numbers have been increasing. It is caused by lungs which are still too immature to produce adequate amounts of surfactant. This surfactant reduces the alveolar surface tension and maintains the alveoli from collapsing. Collapsed alveoli prevent gas exchange and greatly increase work of breathing. Surfactant is a biochemical complex made up mostly of phospholipids such as phosphatidylcholine and phosphatidylglycerol and these, in turn, appear to be synthesized by lysophosphatidylcholine acyltransferase 1 (LPCAT 1). The investigators have previously established that hLPCAT1 mRNA in maternal serum correlates with lamellar body count, a well established clinical marker of fetal lung maturity.

Detailed Description
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OBJECTIVES/AIMS Group 1: Determine the serum levels of hLPCAT1 mRNA in pregnant women from 32- 36+6/7 weeks gestation. More specifically, to determine at what moment in gestation, expression spontaneously begins. Group 2: Determine how (and if) serum hLPCAT1 mRNA changes with administration of a course of steroids by measuring its levels before, 24hrs after the first dose and 24hrs after the second dose of bethamethasone as well as one and two week after the first dose. The investigators seek to understand the effects of the 2nd dose of steroids and determine if, once the hLPCAT1 expression begins, does it continue or does it turn off again after some time from steroid administration. Correlate measures of neonatal outcomes (Apgars, cord gases, need for NICU admission, need for respiratory support, need for ventilator) with levels of hLPCAT1 in labor. METHODOLOGY The first group will consist of patients with normal pregnancies who present for routine prenatal care between 32- 36 6/7 weeks. Once consented and enrolled in the study, participants will give a small (half a teaspoon) blood sample every other week until reaching 37 weeks. In group 2, pregnant women who present for rule-out preterm labor will be offered participation in the study. Blood samples will be collected along with all other relevant clinical labs (in PAX gene tubes) on admission, 24hrs and 48hrs after the course of steroids is initiated. Samples will also be collected 1 and 2 weeks later to see if steroid effect degrades over time. This would have immense clinical implication, especially when it comes to rescue doses. Investigators will also correlate measures of neonatal outcomes (such as apgar scores, blood gases, NICU admission, need to go on respiratory/ventilator support) to the most recent maternal serum hLPCAT1 throughout the study. If the patient delivers more than one week from the last sample, an hLPCAT1 will be acquired during labor. Women with singleton pregnancies and no evidence of diabetes, hypertension, smoking, BMI > 35, Hgb < 10 g/dl or other confounding variables will be admitted to the study. In addition a baseline for hLPCAT1 maternal serum mRNA will be established by testing women from 32 - 36 +6/7 weeks gestation. All tests will consist of a half teaspoon (2.5 ml) blood collection using PAX gene tubes. Consent will be obtained by the PI/Co-PI's and by residents/fellows and the signed consent sheet will become part of the chart. No remuneration will be offered. Investigators will seek 80 volunteers for this study, anticipating an approximate drop-out rate of 50% because of compliance issues and early deliveries.

Official Title
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Effect of Steroid Administration on Maternal Blood Levels of hLPCAT1 mRNA

Conditions
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Fetal Lung Maturity, Respiratory Distress Syndrome in Premature Infant

Intervention / Treatment
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* Other: blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancy, no evidence of diabetes, hypertension, smoking, BMI > 35, Hgb < 10 g/dl or other confounding variables Exclusion Criteria: Smoking, abnormal gestation, multiple gestatio

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women Receiving Antenatal Steroids<br>Group 2: Determine how (and if) serum hLPCAT1 mRNA changes with administration of a course of steroids by measuring its plasma levels before, 24hrs after the first dose and 24hrs after the second dose of bethamethasone as well as one and two week after the first dose. This is accomplished through a simple blood draw. We seek to understand the effects of the 2nd dose of steroids and determine if, once the hLPCAT1 expression begins, does it continue or does it turn off again after some time from steroid administration. | Other: blood draw<br>* Blood draw (2.5mL) to assess mRNA LPCAT1 levels<br>|
| Normal Pregnancy Controls<br>1) Group 1: Determine the plasma levels of hLPCAT1 mRNA in pregnant women from 32- 36+6/7 weeks gestation. This is accomplished through a simple blood draw. More specifically, we seek to find out, at what moment in gestation, expression spontaneously begins. | Other: blood draw<br>* Blood draw (2.5mL) to assess mRNA LPCAT1 levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LPCAT1 mRNA levels in maternal plasma after antenatal steroid administration | The investigators will measure the level of LPCAT1 mRNA in maternal plasma before and after the administration of antenatal steroids. | The time points will be a baseline before steroids, 24h after the first dose, 24h after the second dose, a week after steroids and two weeks after steroids. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants admitted to the NICU with high LPCAT1 mRNA levels | Maternal levels of LPCAT1 mRNA will be measured in labor and compared to the need for admission to NICU. Data gathered from a chart review. | Through study completion, within 2 months | 
| Correlate the LPCAT1 mRNA copy number to need for intubation in the nicu | LPCAT1 mRNA levels in labor will be correlated to need for intubation. Data gathered from a chart review. | Through study completion, within 2 months |