Methods
All live births in Nova Scotia, Canada, and the United States from 2007 to 2020 were included in the study. Data on live births in Canada were obtained from the Nova Scotia Atlee Perinatal Database. This population-based, clinically-focused database, contains information on maternal characteristics, delivery events and neonatal information for all births (with a birth weight of at least 500 gram or gestational age of 20 weeks or more) in the province. Information in the database is routinely abstracted from antenatal and medical charts by trained personnel using standardized forms.14 Data for births in the United States were obtained from the natality files of the National Center for Health Statistics, which includes information on all live birth registrations in the United States.15
ACS use in the Natality database of the United States was defined as “ACS for fetal lung maturation received by the mother before delivery” and available for all live births. The gestational age at ACS administration was unknown in both Canada and the United States. However, in Nova Scotia, information on ACS use in the Nova Scotia Atlee Perinatal Database included the timing of the first dose administered in relation to delivery (viz., first dose received <24 hours prior to delivery, first dose received between 24 hours and 48 hours prior to delivery, first dose received between 48 hours and 7 days prior to delivery, and first dose received >7 days prior to delivery) and this enabled us to distinguish between receipt of a partial course (one dose) versus a complete course (two doses of betamethasone) of ACS. Thus, women who received ACS <24 hours prior to delivery were deemed to have received suboptimal ACS as this represented insufficient time for receipt of a complete single course.16-18 Women who received ACS prophylaxis more than 7 days before preterm delivery at 24 to 34 weeks were also considered to have received less than optimal therapy since the efficacy of ACS in reducing respiratory distress syndrome does not extend beyond 7 days.16-18 We, therefore, categorized ACS use as follows: i) any administration of ACS in the period before delivery; ii) optimal ACS administration i.e., ACS administration between 24 hours to 7 days before delivery to women who delivered a live birth between 24 to 34 weeks of gestation; and iii) suboptimal ACS administration i.e., ACS administration <24 hours or >7 days prior to delivery to women who delivered a live birth between 24 and 34 weeks of gestation. In Nova Scotia, gestational age was based on the following hierarchy: the date of early second trimester ultrasound or the date of the last menstrual period, or a postnatal assessment, and in the United States it was based on the clinical (obstetric) estimate of gestation.
The time span of the study was divided into two periods, 2007-2016 (i.e., the period before and including the year of publication of the ALPS trial) vs 2017-2020 (i.e. the period after the publication of the ALPS trial), with the earlier period used as the reference. Rates of ACS use were also examined by year. The frequency of ACS administration within specific categories of gestational age (<24, 24-27, 28-32, 33-34, 35-36, ≥37 weeks) was assessed by calculating rates per 100 live births within each gestational age category in both Canada and the United States. Odds ratios (OR) were used to quantify temporal changes in ACS use by gestational age.
In Nova Scotia, Canada, we estimated the frequency of ACS administration within categories of maternal and clinical characteristics including mode of delivery. Mode of delivery was categorized as spontaneous vaginal delivery, instrumental vaginal delivery, cesarean delivery in labour, and planned cesarean delivery. Temporal trends were assessed by plotting the frequency of optimal and suboptimal ACS administration using 2-year moving averages over the study period. The rate denominators for optimal and suboptimal administration were the number of live births between 24 and 34 weeks’ gestation. The statistical significance of a linear pattern in annual rates was assessed using the Cochran-Armitage chi-square test for linear trend, and also visually to identify non-linear patterns. The statistical significance of differences was assessed using two-sided P-values and a P-value <0.05 was considered statistically significant. Analyses were performed using SAS software Version 9.2 of the SAS System for Windows ©. The Reproductive Care Program of Nova Scotia and the Research Ethics Board of the IWK Health Centre provided data access and ethics approval, respectively.