Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht and Utrecht University, Utrecht, the Netherlands.
JAMA Netw Open. 2024 Jul 1;7(7):e2424608. doi: 10.1001/jamanetworkopen.2024.24608.
Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination protects newborns against severe pertussis. Data on transplacental antibody transfer on Tdap vaccination before 24 weeks' gestation remain scarce and are particularly relevant for preterm infants to increase the time interval for maternal antibody transfer.
To assess noninferiority of anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) antibody levels at age 2 months in early- to late-term infants following Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation and compared with preterm infants.
DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study included pregnant women aged 18 years or older in birthing centers and hospitals in the Netherlands between August 2019 and November 2021 who received Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation. Women with imminent premature birth were recruited if they had received maternal Tdap vaccination between 20 and 24 weeks' gestation. Blood samples were collected from mothers at delivery, from the umbilical cord, and from infants at age 2 months. Data from infants' blood samples at age 2 months were compared with a reference cohort (recruited between January 2014 and February 2016) of early- to late-term infants of the same age whose mothers had received Tdap vaccination between 30 0/7 and 33 0/7 weeks' gestation.
Maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation or 30 0/7 and 33 0/7 weeks' gestation.
The primary outcome was the geometric mean concentration (GMC) of anti-PT IgG antibodies in early- to late-term infants (≥37 0/7 weeks' gestation) at age 2 months, comparing maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' vs 30 0/7 and 33 0/7 weeks' gestation (reference cohort). Anti-PT GMC in 2-month-old infants born preterm (<35 0/7 weeks' gestation) compared with early- to late-term infants after maternal Tdap vaccination between 20 and 24 weeks' gestation was a secondary outcome.
In total, 221 women who delivered 239 offspring were enrolled in the study; 66 early- to late-term infants (median gestational age [GA], 40.6 weeks [IQR, 39.8-41.0 weeks]; 38 [57.6%] male) and 73 preterm infants (median GA, 32.1 weeks [IQR, 29.5-33.0 weeks]; 42 [54.5%] female) had blood samples collected at 2 months of age. Anti-PT GMC was 14.7 IU/mL (95% CI, 10.6-20.4 IU/mL) in early- to late-term infants following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 27.3 IU/mL (95% CI, 20.1-37.1 IU/mL) in 55 infants in the reference group (median GA, 40.3 [IQR, 39.1-41.0]; 33 [60.0%] female). The mean anti-PT GMC in preterm infants in the study group was 11.2 IU/mL (95% CI, 8.1-15.3 IU/mL) (P = .23 compared with early- to late-term infants).
In this cohort study, 2-month-old preterm and early- to late-term infants showed significantly lower anti-PT antibody levels following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation; preterm and early- to late-term infants had similar anti-PT antibody levels, but both groups showed significantly lower antibody levels compared with the reference group. Epidemiological research should investigate whether maternal Tdap vaccination before 24 weeks' gestation provides sufficient protection against clinical pertussis, particularly in preterm infants, as long as no correlate of protection is available.
母体破伤风、白喉和无细胞百日咳（Tdap）疫苗可保护新生儿免受严重百日咳的侵害。关于 24 周妊娠前 Tdap 疫苗接种时胎盘抗体转移的数据仍然很少，对于早产儿尤其重要，因为这可以增加母体抗体转移的时间间隔。
评估在 20 至 24 周妊娠期间接受 Tdap 疫苗接种的晚期至早期婴儿在 2 个月龄时抗百日咳毒素（anti-PT）免疫球蛋白 G（IgG）抗体水平与 30 至 33 周妊娠和早产儿的非劣效性。
设计、地点和参与者：这是一项前瞻性、多中心队列研究，纳入了 2019 年 8 月至 2021 年 11 月期间在荷兰分娩中心和医院的 18 岁或以上的孕妇，这些孕妇在 20 至 24 周妊娠期间接受了 Tdap 疫苗接种。如果有即将早产的孕妇在 20 至 24 周妊娠期间接受了母体 Tdap 疫苗接种，则招募她们。母亲在分娩时、脐带和婴儿 2 个月龄时采集血样。将婴儿 2 个月龄时的血样数据与参考队列（2014 年 1 月至 2016 年 2 月招募）进行比较，参考队列是在相同年龄段接受了 30 至 33 周妊娠 Tdap 疫苗接种的晚期至早期婴儿。
20 至 24 周妊娠或 30 至 33 周妊娠期间接受母体 Tdap 疫苗接种。
主要结局是 2 个月龄时晚期至早期婴儿（≥37 周妊娠）的抗-PT IgG 抗体几何平均浓度（GMC），比较了 20 至 24 周妊娠与 30 至 33 周妊娠（参考队列）之间的 Tdap 疫苗接种（母亲）。20 至 24 周妊娠时接受母体 Tdap 疫苗接种的早产儿（<35 周妊娠）与晚期至早期婴儿在 2 个月龄时的抗-PT GMC 比较是次要结局。
共有 221 名分娩 239 名婴儿的孕妇入组研究；66 名晚期至早期婴儿（中位胎龄[GA]，40.6 周[IQR，39.8-41.0 周]；38[57.6%]为男性）和 73 名早产儿（中位 GA，32.1 周[IQR，29.5-33.0 周]；42[54.5%]为女性）在 2 个月龄时采集了血样。与 55 名在参考组接受 Tdap 疫苗接种的婴儿（中位 GA，40.3 [IQR，39.1-41.0]；33[60.0%]为女性）相比，在 20 至 24 周妊娠期间接受 Tdap 疫苗接种的晚期至早期婴儿的抗-PT GMC 为 14.7 IU/mL（95%CI，10.6-20.4 IU/mL）（中位数 GA，40.3 [IQR，39.1-41.0]；33[60.0%]为女性）。研究组早产儿的平均抗-PT GMC 为 11.2 IU/mL（95%CI，8.1-15.3 IU/mL）（与晚期至早期婴儿相比，P=0.23）。
在这项队列研究中，与 30 至 33 周妊娠相比，20 至 24 周妊娠期间接受 Tdap 疫苗接种的早产儿和晚期至早期婴儿在 2 个月龄时的抗-PT 抗体水平明显较低；早产儿和晚期至早期婴儿的抗-PT 抗体水平相似，但两组的抗体水平均明显低于参考组。由于没有保护相关性，流行病学研究应调查 24 周妊娠前的母体 Tdap 疫苗接种是否能为临床百日咳提供足够的保护，特别是对早产儿。
