Preterm Birth Frequency and Associated Outcomes From the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Trial of the Bivalent Respiratory Syncytial Virus Prefusion F Protein Vaccine

Abstract

Objective: To describe preterm birth frequency and newborn and infant outcomes overall and among preterm children in the MATISSE (Maternal Immunization Study for Safety and Efficacy) trial of maternal vaccination with bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) to protect infants against severe RSV-associated illness.

Methods: MATISSE was a global, phase 3, randomized, double-blind trial. Pregnant individuals received single injections of RSVpreF or placebo. Adverse events of special interest, including preterm birth (gestational age less than 37 weeks) and low birth weight (2,500 g or less), were collected through 6 months after delivery (pregnant participants) and from birth through age 12 or 24 months (pediatric participants).

Results: Overall, 7,386 pregnant participants received RSVpreF (n=3,698) or placebo (n=3,688); 7,305 newborns and infants were included in the analysis. Most children in both groups were born full term (more than 93%) with normal birth weight (95% or higher). Newborn and infant outcomes, including rates of low birth weight and neonatal hospitalization, were favorable and comparable between groups. Preterm birth rates were 5.7% in the RSVpreF arm and 4.7% in the placebo arm (relative risk [RR] 1.20, 95% CI, 0.98-1.46); most were late preterm. Newborn and infant outcomes, including rates of low birth weight and neonatal hospitalization, were comparable between groups. Twenty-two newborn or infant deaths occurred during the study (RSVpreF n=8, placebo n=14). When stratified by income region, preterm birth rates in RSVpreF and placebo recipients were both 5.0% in high-income countries. Rates in non-high-income countries were 7.0% and 4.0% in the RSVpreF and placebo groups, respectively, and 8.3% and 4.0% in South Africa (RR 2.06, 95% CI, 1.21-3.51).

Conclusion: In this study of maternal RSVpreF vaccination, no clinically significant increase in adverse events of special interest, including preterm birth, low birth weight, or neonatal hospitalization, was observed among pregnant people in the overall analysis. In subgroup analysis of non-high-income countries, an elevated risk of preterm birth was observed. More research is needed to better ascertain preterm delivery risk factors, particularly aimed at minimizing disparities among geographic regions.

Funding source: This study was sponsored by Pfizer.

Clinical trial registration: ClinicalTrials.gov , NCT04424316.

Fig. 1.. Relative risk for newborn and infant outcomes (A) and newborn and infant deaths during the study (B). Shown are data from the newborn and infant safety population. Serious adverse event (SAE)–related hospitalizations were within the neonatal period (ie, 4 weeks). Low Apgar scores were a first score lower than 4 or last score lower than 7. AE, adverse event; RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine.

Fig. 2.. Cumulative distribution, case counts, and cumulative case counts of gestational age at birth among newborns and infants born at less than 37 weeks of gestation. RSVpreF, respiratory syncytial virus prefusion F protein–based vaccine.

Fig. 3.. Preterm births by gestational age (GA) at vaccination. Shown are data from the infant safety population. Numbers above the error bars are the preterm birth rate (less than 37 weeks of gestation) overall and by GA at vaccination. Also shown is the relative risk (95% CI). In the overall and less than 28 weeks of gestation at vaccination groups, the rate of GA at birth of 24–less than 28 weeks was less than 0.1% (n=1) in both the respiratory syncytial virus prefusion F protein–based vaccine (RSVpreF) and placebo groups.

Fig. 4.. Preterm births by income region (A) and relative risk for preterm birth overall and by country (B). Shown are data from the newborn and infant safety population. A. Numbers above the bars are the preterm birth rate (less than 37 weeks of gestational age [GA]) overall and by World Bank income region. Also shown is the relative risk (95% CI). In the overall group, the rate of GA at birth of 24–less than 28 weeks was less than 0.1% (n=1) in both the respiratory syncytial virus prefusion F protein–based vaccine (RSVpreF) and placebo groups. In the high-income group, the preterm birth rate at a GA at birth of 24–less than 28 weeks was less than 0.1% (n=1) in the placebo group. In the non–high-income group, the preterm birth rate at a GA at birth of 24–less than 28 weeks was less than 0.1% (n=1) in the RSVpreF group. In the upper-middle–income group, the preterm birth rate at a GA at birth of 24–less than 28 weeks was less than 0.1% (n=1) in the RSVpreF group. B. Countries with more than five preterm births overall. Countries included in each income region are summarized in Appendix 2, available online at http://links.lww.com/AOG/D944. n, number of newborns and infants born preterm; N, total number of infants.