68 - Peripheral Markers of HPA-axis Function in Neonates Exposed to Betamethasone Remote from Delivery

Publication Number: 2065.68

Lauren A. Buckley, University of Minnesota Medical School, Saint Paul, MN, United States; Raghavendra Rao, University of Minnesota Medical School, Minneapolis, MN, United States; Sarah Wernimont, University of Minnesota Medical School, Minneapolis, MN, United States

Background: Antenatal corticosteroids including betamethasone (BMZ) are associated with improved outcomes for preterm infants if delivery occurs between 1-7 days of administration. However, due to the difficulty of predicting preterm delivery, up to 70% of BMZ-exposed infants are born outside the window of optimal efficacy and up to 40% are born at term. There is concern for a negative impact of mistimed BMZ, particularly for term-born infants, due to reports of impaired cortisol-reactivity and increased incidence of mental disorders including autism spectrum disorder and attention deficit hyperactivity disorder following antenatal corticosteroid exposure.

Objective: The objective of this study was to determine whether remote BMZ exposure alters circulating hypothalamic-pituitary-adrenal (HPA) axis hormones as measured in umbilical cord blood (UCB). We hypothesized that UCB cortisol and ACTH levels would be suppressed in neonates with remote BMZ exposure.

Design/Methods: UCB from neonates exposed to BMZ ≥3 weeks prior to delivery (BMZ, N=8) and unexposed control pregnancies (CON, N=24) were obtained from the UMOM:GOPHER maternal-infant biobank at the University of Minnesota. Clinical variables related to maternal health status, pregnancy complications, neonatal outcomes and timing of BMZ exposure were abstracted from the biobank database. BMZ latency interval was defined as the number of weeks between the most recent BMZ dose and delivery. UCB cortisol and pituitary hormone levels (adrenocorticotropic hormone (ACTH), Agouti-Related Protein (AgRP), growth hormone (GH)) were quantified by Luminex Multiplex assay. Statistical outliers were identified using Grubbs test and were removed. Student's t-tests or Wilcoxon rank-sum tests were used for comparison of continuous variables, and Chi-square or Fisher's exact tests were used for comparison of categorical variables.

Results: Gestational age at birth (37.1 vs. 39.0 weeks', p=0.008) and birth weight (3.02 vs. 3.45 kg, p=0.02) were lower in the BMZ group compared to CON group. Other baseline characteristics were similar between groups (Table 1). The initial dose of BMZ was administered between 29.1 and 33.3 weeks' gestation (median = 31.2 weeks). BMZ latency interval ranged from 3.0 to 10.1 weeks (median = 4.9 weeks). UCB cortisol, AgRP, GH, and ACTH were not statistically different between groups (Figure 1).

Conclusion(s): Remote BMZ exposure does not significantly affect fetal HPA-axis hormone concentrations in UCB at time of delivery.

Table 1. Pregnancy and Birth Characteristics
CON, control; BMZ, betamethasone-exposed; SD, standard deviation; IQR, interquartile range.

Figure 1.
Comparison of umbilical cord blood hormone levels in control infants (CON, N=23-24) versus infants exposed to antenatal betamethasone ≥3 weeks prior to delivery (BMZ, N=7-8). A. Cortisol. B. Agouti-Related Protein (AgRP). C. Growth Hormone (GH). D. Adrenocorticotropin (ACTH).