背景:在2023年初,当Omicron成为关注的变种时,我们表明,孕妇接种疫苗降低了严重COVID-19相关并发症的风险,孕产妇发病率和死亡率。
目的:分析妊娠期间COVID-19对新生儿的影响以及母亲接种COVID-19对新生儿结局的影响,当Omicron成为关注的变种时。
方法:INTERCOVID-2022是一个大型的,prospective,观察性研究,在18个国家的40家医院进行,从2021年11月27日(世界卫生组织宣布Omicron为关注变种后的第二天)到2022年6月30日,评估妊娠期间COVID-19对孕产妇和新生儿结局的影响,以及疫苗有效性(VE)。在怀孕期间被诊断为实验室确诊的COVID-19的女性与两名“未确诊”的女性进行了比较,不匹配的妇女在怀孕或分娩时同时和连续招募。对母亲/新生儿进行随访,直到出院。主要结果是新生儿COVID-19阳性检测,严重新生儿发病指数(SNMI),严重围产期发病率和死亡率指数(SPMMI),早产,新生儿死亡,转诊至新生儿重症监护病房(NICU),和新生儿期的疾病。VE估计是根据产妇风险状况进行调整的。
结果:我们招募了4707名新生儿,其中1577名(33.5%)母亲被诊断为COVID-19,3130名(66.5%)母亲未被诊断为COVID-19。在确诊的母亲中,642人(40.7%)未接种疫苗,147人(9.3%)部分接种疫苗,551(34.9%)完全接种疫苗,237人(15.0%)也接种了加强疫苗。与未接种疫苗的母亲相比,接种疫苗的母亲的新生儿被诊断出患有COVID-19的风险不到一半(RR=0.46;95CI=0.23,0.91);他们的早产率也最低,医学上指示的早产,呼吸窘迫综合征和NICU天数。未接种疫苗的母亲的新生儿与未诊断的母亲相比,新生儿死亡的风险加倍(RR=2.06;95%CI=1.06,4.00)。疫苗接种与任何先天性畸形无关。尽管所有疫苗都提供了防止新生儿检测阳性的保护,加强疫苗接种母亲的新生儿的VE显著最高(64%;95%CI=10-86%);仅mRNA疫苗的VE没有那么高.针对中度/重度新生儿结局的VE要低得多:加强疫苗接种组(所有疫苗)为13%,在完全和加强疫苗接种组中分别有25%和28%,分别(仅mRNA疫苗)。当孕妇在出生前100天(14周)或更短时间接种疫苗时,疫苗在保护新生儿方面相当有效;此后,风险增加,且在200天(29周)后更高..最后,没有研究新生儿的做法,包括皮肤接触和直接母乳喂养,增加了感染新生儿的风险。
结论:当Omicron成为关注的变体时,未接种疫苗的母亲的新生儿新生儿死亡风险增加.接种疫苗的母亲的新生儿早产和不良新生儿结局的风险降低。由于COVID-19疫苗的保护作用随着时间的推移而降低,为了确保新生儿得到最大限度的预防COVID-19的保护,母亲应该在预计分娩日期前不超过14周接受疫苗或加强剂量。
BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality.
OBJECTIVE: This
study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern.
METHODS: INTERCOVID-2022 was a large, prospective, observational
study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile.
RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns.
CONCLUSIONS: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.