Importance The standard schedule of national immunization programs for infants may not be sufficient to protect extremely and very preterm infants. Objective To evaluate the immunogenicity of routine vaccinations administered to preterm infants. Design, Setting, and Participants A multicenter, prospective, observational cohort study of preterm infants stratified according to gestational age recruited from 8 hospitals across the Netherlands between October 2015 and October 2017, with follow-up until 12 months of age (October 2018). In total, 296 premature infants were enrolled and compared with a control group of 66 healthy term infants from a 2011 study, immunized according to the same schedule with the same vaccines. Exposures Three primary doses of the diphtheria-tetanus toxoids-acellular pertussis-inactivated poliomyelitis-Haemophilus influenza type b-hepatitis B combination vaccine were given at 2, 3, and 4 months after birth followed by a booster at 11 months and a 10-valent pneumococcal conjugate vaccine at 2, 4, and 11 months after birth. Main Outcomes and Measures Primary end points were (1) proportion of preterm infants who achieved IgG antibody against vaccine antigens at concentrations above the internationally defined threshold for protection after the primary series and booster dose and (2) serum IgG geometric mean concentrations after the primary series and booster vaccination. Proportions and geometric mean concentrations were compared in preterm infants and the control group of term infants. Results Of 296 preterm infants (56.1% male; mean gestational age, 30 weeks), complete samples before vaccination, 1 month after the primary series, and 1 month after the booster were obtained from 220 preterm infants (74.3%). After the primary series, the proportion of preterm infants across all gestational age groups who achieved protective IgG antibody levels against pertussis toxin, diphtheria, tetanus and 6 of 10 pneumococcal serotypes varied between 83.0% and 100%, Haemophilus influenzae type b between 34.7% and 46.2% (40.6% among all preterm infants overall), and pneumococcal serotypes 4, 6B, 18C, and 23F between 45.8% and 75.1%. After the booster dose, protective antibody levels were achieved in more than 95% of all preterm groups, except for Haemophilus influenzae type b (88.1%). In general, geometric mean concentrations of all vaccine-induced antibodies were significantly lower in all preterm infants vs term infants, except for pertussis toxin and pneumococcal serotypes 4 and 19F after the primary series and booster vaccination. Conclusions and Relevance Among preterm infants, administration of routine vaccinations during the first year of life was associated with protective antibody levels against most antigens in the majority of infants after the primary series and booster, except for Haemophilus influenzae type b. However, antibody concentrations were generally lower among preterm infants compared with historical controls.

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常规婴儿疫苗接种与早产婴儿抗体水平的关联

重要性 国家婴儿免疫计划的标准时间表可能不足以保护极早产儿和极早产儿。目的评价早产儿常规接种疫苗的免疫原性。设计、设置和参与者 2015 年 10 月至 2017 年 10 月期间从荷兰 8 家医院招募的根据胎龄分层的早产儿多中心、前瞻性、观察性队列研究，随访至 12 个月大（2018 年 10 月）。总共招募了 296 名早产儿，并与 2011 年一项研究中的 66 名健康足月婴儿的对照组进行了比较，这些婴儿按照相同的时间表使用相同的疫苗进行免疫。暴露 在出生后 2、3 和 4 个月时分别接种了三剂主要剂量的白喉-破伤风类毒素-脱细胞百日咳-灭活脊髓灰质炎-流感嗜血杆菌-乙型肝炎联合疫苗，然后在 11 个月时接种了加强剂和 10 价疫苗在出生后 2、4 和 11 个月接种肺炎球菌结合疫苗。主要结果和指标 主要终点是 (1) 在主要系列和加强剂量后获得针对疫苗抗原的 IgG 抗体浓度高于国际定义的保护阈值的早产儿比例，以及 (2) 初次接种后血清 IgG 几何平均浓度系列和加强疫苗接种。比较早产儿和足月儿对照组的比例和几何平均浓度。结果 296 名早产儿（男性 56.1%；从 220 名早产儿 (74.3%) 获得平均胎龄，30 周）、接种前、初级系列后 1 个月和加强接种后 1 个月的完整样本。在初级系列之后，所有孕龄组中达到针对百日咳毒素、白喉、破伤风和 10 种肺炎球菌血清型中的 6 种的保护性 IgG 抗体水平的早产儿比例在 83.0% 和 100% 之间变化，b 型流感嗜血杆菌在 34.7% 和46.2%（在所有早产儿中占 40.6%），肺炎球菌血清型 4、6B、18C 和 23F 介于 45.8% 和 75.1% 之间。在加强剂量后，除 b 型流感嗜血杆菌 (88.1%) 外，所有早产组中 95% 以上都达到了保护性抗体水平。一般来说，所有早产儿的所有疫苗诱导抗体的几何平均浓度均显着低于足月儿，但百日咳毒素和肺炎球菌血清型 4 和 19F 在初级系列和加强疫苗接种后除外。结论和相关性 在早产儿中，除了 b 型流感嗜血杆菌外，大多数婴儿在出生后第一年的常规疫苗接种与针对大多数抗原的保护性抗体水平相关。然而，与历史对照相比，早产儿的抗体浓度通常较低。除了 b 型流感嗜血杆菌外，大多数婴儿在出生后第一年进行常规疫苗接种与针对大多数抗原的保护性抗体水平相关。然而，与历史对照相比，早产儿的抗体浓度通常较低。除了 b 型流感嗜血杆菌外，大多数婴儿在出生后第一年进行常规疫苗接种与针对大多数抗原的保护性抗体水平相关。然而，与历史对照相比，早产儿的抗体浓度通常较低。