Risk factors and outcomes of delayed completion of the hexavalent 3 + 1 immunisation series in German preterm infants – an observational study

Although very low birthweight infants (VLBWI, birthweight < 1500 g) are at increased risk of infectious diseases, they frequently receive primary vaccinations with the hexavalent vaccine (DTaP-IPV-Hib-HepB) later than recommended. Detailed data on the adherence to the hexavalent 3 + 1 immunisation schedule (at 2, 3, 4 and 11 months of age) in German VLBWI are scarce. This study evaluated the timeliness of the primary hexavalent vaccination series among VLBWI from the German Neonatal Network (GNN) and aimed at identifying risk factors and outcomes associated with delayed series completion. As part of the multicentre, population-based GNN, N = 3,394 VLBWI born between 2009 and 2016 underwent a follow-up examination at 6 years of age, including documentation of vaccination certificates. Uni- and multivariate analyses were performed to evaluate the timely completion of the 3 + 1 schedule for hexavalent immunisation and to examine risk factors and outcomes associated with delays. Despite a high overall hexavalent vaccination coverage of more than 97% by six years of age, only 3.3% (n = 108) of VLBWI received the hexavalent booster at the recommended age of 11 months, and 41.6% (n = 1,373) had completed the primary vaccination series by 15 months of age. Progressive delays were observed across subsequent doses, with the lowest schedule-adherent coverage recorded for the booster dose. A timely first hexavalent vaccination (OR 0.61; 95% CI 0.52–0.72) was protective against delayed series completion, while bronchopulmonary dysplasia (BPD) was associated with a delay of the booster beyond 15 months of age (OR 1.31; 95% CI 1.07–1.61). Timely series completion was associated with decreased risk of incomplete vaccine protection at daycare entry (OR 0.09; 95% CI 0.07–0.14) and a lower rate of parent-reported pertussis within the first 6 years of life (OR 0.47; 95% CI 0.24–0.90). Our data demonstrate significant delays in the primary vaccination series which were most pronounced at the booster dose and particularly affects the most susceptible infants, i.e., VLBWI with BPD. However, vulnerable preterm infants would benefit greatly from timely vaccinations to ensure optimal protection by the time they are increasingly exposed to infectious pathogens, as for instance upon entry into childcare settings.