Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles


To estimate the effect of antenatal glucocorticoid administration on fetal lung maturity in pregnancies with known fetal lung immaturity between the 34th and 37th weeks of gestation.

Study Design

Pregnancies between 34 0/7 and 36 6/7 weeks undergoing amniocentesis to determine fetal lung maturity were targeted. Women with negative results (TDx-FLM-II <45 mg/g) were randomly assigned to intramuscular glucocorticoid injection or no treatment. A repeat TDx-FLM-II test was obtained 1 week after enrollment.


Thirty-two women who met inclusion criteria were randomly assigned. Seven women delivered within a week of testing for fetal lung maturity, and were excluded from the analysis. Ten received glucocorticoid and 15 did not. Women assigned to glucocorticoids had a mean increase TDx-FLM-II in 1 week of 28.37 mg/g. Women assigned to no-treatment had an increase of 9.76 mg/g ( P < .002).


A single course of intramuscular glucocorticoids after 34 weeks in pregnancies with documented fetal lung immaturity significantly increases TDx- FLM-II.

Respiratory distress syndrome (RDS) is a major cause of morbidity in the newborn, and is ranked as 1 of the leading causes of infant deaths in the United States. It has been demonstrated that treatment with corticosteroids results in a reduction in the rate of RDS in pregnancies at risk to deliver preterm. Treatment with corticosteroids have also been suggested to reduce the rates of intraventricular hemorrhage, necrotizing enterocolitis, neonatal mortality, and systemic infection in the first 48 hours of life. Because of these benefits, current recommendations from the American College of Obstetricians and Gynecologists call for a single course of corticosteroids to all pregnant women between 24 and 34 weeks of gestation who are at risk for preterm delivery.

Although it is accepted that enhancement of pulmonary function via antenatal steroids is recommended for pregnancies at risk for preterm birth at less than 34 weeks, less is known about the effects of steroids among women at more advanced gestational ages. A metaanalysis of published randomized trials on antenatal steroid therapy indicated limited number of patients participating after 34 weeks. Even though the incidence of RDS is lower after 34 weeks, late-preterm infants (defined as birth between 34 0/7 and 36 6/7 ) are at higher risk of complications as compared with term infants and the benefit of steroids for enhancement of fetal lung maturity during this period remains to be determined.

The assessment of fetal lung maturity is useful for determining the timing of delivery in patients with complicated pregnancies. Amniocentesis is commonly performed after 34 weeks in cases in which continuing pregnancy may present substantial maternal and fetal risks. Examples of these complicated pregnancies include a history of bleeding placenta previa, a history of a previous classical cesarean delivery, a history of previous uterine surgery, or in diabetic patients with suboptimal metabolic control. Although the interpretation of a mature fetal lung maturity test is straightforward, there is no consensus on the timing and course of action after an immature result. In our previous analysis, we assessed the weekly increment of TDx-FLM II between 31 and 38 weeks and reported an average 14.4 mg/g per week (95% confidence interval [CI], 12.3–16.5) increase. The effect of steroids among women who have a negative fetal lung maturity test after 34 weeks has not been sufficiently addressed. Methods to accelerate pulmonary maturity in cases of documented fetal pulmonary immaturity after 34 weeks would potentially reduce the likelihood of RDS when preterm delivery is indicated. The purpose of our study was to test the hypothesis that antenatal glucocorticoid administration in pregnancies with known fetal lung immaturity between the 34th and 37th weeks of gestation might accelerate fetal lung maturity.

Materials and Methods

This randomized controlled study was conducted at Barnes-Jewish Hospital in St. Louis, MO, between May 2003 and May 2008. The Human Studies Committee at Washington University School of Medicine approved the protocol and informed consent was obtained from eligible patients. Women with singleton gestations between 34 0/7 and 36 6/7 weeks with an immature TDx-FLM-II test (<45 mg/g) after a clinically indicated amniocentesis to test for fetal lung maturity were invited to participate. Gestational age was calculated based on the last menstrual period (LMP) and correlated to an ultrasound measurement. The LMP was used to assign the gestational age in cases where the ultrasound correlated within ± 7 days. For discrepancies between the LMP and the ultrasound dating >7 days, the ultrasound-assigned gestational age was used. For patients for whom the LMP was uncertain, the ultrasound at ≤20 weeks was used for gestational age assignment.

Patients excluded were those with multiple gestations, ruptured membranes, uncertain gestational ages, steroid treatment previously in the current pregnancy, delivery before completion of the steroid course, and those who were unwilling or unable to comply with the study protocol. Block randomization was performed, which ensured equal numbers of steroid and no steroid assignments, with sealed envelopes twice the target number of subjects. Eligible patients were consented and randomly assigned into either the treatment group or the no-treatment group.

The treatment group received corticosteroids, either betamethasone 12 mg intramuscular (IM) injection every 24 hours for 2 doses or dexamethasone 6 mg, IM every 12 hours for 4 doses. This treatment is identical to those given to patients between 24 and 34 weeks’ gestation at risk for preterm delivery. Both the treatment and the no-treatment group underwent a repeat test for fetal lung maturity 7 days after the initial sampling. This was performed by either amniocentesis or, if it occurred after 7 days, directly at the time of delivery. Patients undergoing cesarean delivery had amniotic fluid sampled at the time of their hysterotomy. Patients delivering vaginally had fluid taken from a vaginal pool at the time of artificial rupture of membranes. Patients were excluded for preterm delivery in <7 days after the initial amniocentesis.

Whereas different laboratory markers, lecithin-to-sphingomyelin ratio (L/S), presence of phosphatidylglycerol (PG), lamellar body count, and surfactant-to-albumin ratio (TDx-FLM-II), may be used to determine fetal lung maturity, the TDx-FLM-II is the test of choice at our institution. When fetal lung maturity is defined as >45 mg/g, we found 100% sensitivity (no cases of RDS) and 90% specificity for assessment of a mature result. The TDx-FLM-II test was found to be more sensitive with improved negative predictive values compared with L/S and had a more rapid turnaround time and lower cost compared with L/S and PG.

Our primary outcome was the percent with positive lung maturity test results (TDx-FLM-II >45 mg/g) in 1 week between the 2 groups. Secondary outcomes included increase in TDx-FLM-II value between the 2 groups as well as neonatal intensive care unit (NICU) admissions, duration of NICU stay, neonatal hyaline membrane disease, and any maternal complications associated with corticosteroid administration. A sample size calculation was performed for the primary outcome variable based on the results of earlier studies evaluating amniotic fluid indices of fetal lung maturity. One study of amniotic fluid fetal pulmonary phospholipids revealed a spontaneous weekly conversion of 18% from an immature to a mature result between 34 and 37 weeks gestation. A metaanalysis showed a marked reduction in RDS in infants delivered between 24 hours and 7 days after corticosteroid administration (odds ratio [OR] for RDS, 0.35; 95% CI, 0.26–0.46). This was extrapolated to a 51% mature result in the steroid group compared with 18% in the control group. Assuming an alpha of .05 for a 2-tailed test (given steroids could increase or potentially decrease TDx-FLM-II) and a power of 0.8, a sample size of 38 women was required in each arm of the study. Data were analyzed with STATA version 9.0 using a paired t test, Fisher’s exact test, and χ 2 test where appropriate. P < .05 was considered statistically significant.


Thirty-two women who met the inclusion criteria were randomly assigned. Thirteen patients were randomly assigned to the steroid arm and 19 patients were randomly assigned to the no-treatment arm. Seven women, 3 in the steroid arm and 4 in the no-treatment group, delivered within 7 days of their initial testing for fetal lung maturity and were therefore excluded from the analysis. Ten women receiving IM steroids and 15 receiving no-treatment were analyzed ( Figure 1 ). There were no significant differences between the 2 groups with respect to patient age, gestational age at first amniocentesis, race and delivery mode ( Table 1 ). There were more women with diabetes and hypertension in the no-treatment group, but this was not statistically significant.

Jul 7, 2017 | Posted by in GYNECOLOGY | Comments Off on Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles
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