Low Cord Blood Titers Are Associated with Prolonged Maternal RSV Antibody Half-Lives in Preterm Infants
Joukje E Willemsen, Emily W E M Phijffer, Joanne G Wildenbeest, Larry J Anderson, Binh Ha, Ranjini Sankaranarayanan, Floris Groenendaal, Kitty W M Bloemenkamp, José A M Borghans, Julia Drylewicz, Louis BontAbstract
Background
Preterm infants are at higher risk of severe RSV infection, partially because of reduced placental transfer of maternal antibodies (Abs). Increased risk of severe infection persists in the first year of life. This study evaluates the postnatal kinetics of RSV neutralizing antibodies in preterm and full-term infants born to unvaccinated mothers.
Methods
We enrolled infants with a gestational age (GA) of 24-42 weeks born in hospital from RSV-unvaccinated mothers. Serum was collected at birth (cord blood), 1–2 weeks, and 4–8 weeks. Linear mixed-effects models were used to estimate half-lives of RSV-neutralizing Abs in relation to GA and cord blood titer. Analyses were repeated for total serum IgG1 to confirm the robustness of our findings.
Results
Of 169 infants, 95 were born preterm (<37 weeks GA, including 53 neonates <32 weeks GA). Premature birth was related to prolonged half-life of RSV-neutralizing Abs (∼79 days very preterm to ∼30 days in term infants). The inverse association between gestational age and antibody half-life was largely accounted for by an inverse association between cord blood Ab levels and Ab half-life. A doubling in cord blood titers led to a reduction in half-life of ∼20% for RSV neutralizing Abs and ∼32% for IgG1.
Conclusions
Postnatal antibody half-life depends on starting levels: higher titers decline faster. If our observation would be replicated for vaccine-induced Abs, the difference in vaccine protection between preterm and term infants may be smaller than anticipated.