COVID-19造成了全球的疫情,孕妇相比非妊娠人群,更易感染呼吸道疾病和严重肺炎[1],且妊娠使感染后风险更高[2],因此,COVID-19疫情中母胎健康需要引起特别注意。
疫情期间包括孕产妇在内的所有人的生活方式发生了很大改变,由于防疫措施和对感染的担心,孕妇在妊娠期间的产检方式发生变化[3-8];对自身及胎儿感染及社交隔离的担忧也导致孕妇的焦虑和抑郁率显著升高,这可能会导致流产、早产、出生体重降低和新生儿窒息等一系列不良围产结局[9-10]。尽管国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)建议以线上咨询弥补常规产检的不足[11],但疫情影响仍备受关注。本文综述了新冠疫情对未感染孕妇围产期结局的影响,纳入的围产结局包括妊娠期糖尿病、妊娠期高血压、胎膜早破、早产、出生体重、胎儿窘迫、死胎等指标。
妊娠期并发症中最常见的是妊娠期高血压和妊娠期糖尿病(gestational diabetes mellitus,GDM)。其中,一项单中心研究发现[5],疫情期间南京市妊娠期高血压的发病率显著增高,这可能与焦虑等精神状态的改变有关[12]。McDonnell等[13]对都柏林一家三级医院2020年分娩的8 000余例孕产妇资料进行了回顾性研究,妊娠高血压疾病的发病率从1月份的4.4%上升至疫情爆发期的7.1%。但Ranjbar等[14]回顾性分析伊朗德黑兰疫情前1 287例孕产妇和疫情期间1 216例孕产妇,疫情前后妊娠期并发症,如子痫,妊娠期高血压、GDM等发生率并未发生变化。Chmielewska等[15]对于6项研究[5,16-20]的meta分析也认为妊娠相关高血压疾病(hypertensive disorders in pregnancy,HDP)、GDM的风险在疫情期间没有显著差异(OR=1.16,95%CI:0.75～1.79,I2=81%)。
Zanardo等[21]对于意大利疫情前533例和疫情后637例孕产妇的回顾性研究发现疫情后GDM的风险显著增高,这可能与疫情期间孕妇压力增加有关。而Fernández 等[22]发现,Ⅰ型糖尿病患者的血糖控制更为有效。一般认为疫情期间居家办公使其饮食时间更可控,食物更健康,并且有更多的时间关注和调整药物[23-25]。糖尿病作为呼吸道疾病感染的高危因素,也使得患者增强了自我管理意识。但值得注意的是,疫情期间,GDM和妊娠期高血压的发病率可能被低估[16]。孕妇的产前检查次数变少[8,26];妊娠高血压和妊娠糖尿病是否得到充分诊断值得商榷;疫情期间转诊模式的变化,也可能对单中心的结果产生影响[16]。
早产也是争议的焦点问题之一,Bian等[27]对于上海164 107例单胎妊娠孕产妇队列进行研究,认为疫情期间早产率整体下降,但仅在中晚期早产(32周～36+6周)亚组中具有统计学意义,而管控措施解除后,早产率逐渐恢复。Yang等[28]纳入了45项研究,疫情期间1 843 665例妊娠和疫情前23 564 552例妊娠,有25项单中心研究认为早产率有所下降(25项研究,未调整OR=0.90,95%CI:0.86～0.96),但较大的区域性研究中并未发现早产率下降(10项研究,未调整OR=0.99,95%CI:0.95～1.02),早产发生率变化的差异可能与疫情期间孕妇转诊模式的改变有关。Chmielewska等[15]的一项荟萃研究分析则认为高收入国家早产和自发早产发病率减少,(OR=0.91,95%CI:0.84～0.99 vs.OR=0.81,95%CI:0.67～0.97);lemon等[29]认为自然早产率的下降仅限于白人孕妇和居住条件良好的孕妇。
疫情期间,多国政府制定了用于遏制新冠病毒传播的居家隔离措施,或在管控期间减少公共交通及产前诊断可及性[30],但封锁政策对高收入国家和中低收入国家的影响不尽相同[15]。疫情期间,高收入国家佩戴口罩、社交隔离、卫生意识的提高在一定程度上减少了与病原体的接触,降低了孕妇感染常见传染病的风险[31]。此外,疫情期间,孕妇居家饮食次数增多,营养的摄入显著改良[32];疫情期间空气污染的减少都有可能导致早产率的降低[33-34]。而资源匮乏地区则报告了更多由于疫情冲击导致的医疗服务短缺、经济负担加重[35-36]。此外,妊娠期压力、焦虑与子宫动脉阻力增加和子宫血流量减少有关,从而导致早产的风险增加[37]。早产发生率变化的差异也可能与疫情期间孕妇转诊模式的改变有关,三级转诊中心接受的早产孕妇可能有所减少,导致单中心的数据存在偏倚的可能[17]。
此外,很多研究都关注到新生儿出生体重的变化,爱尔兰利默里克大学妇产科医院30 705例新生儿中,极低出生体重儿(即<1 500 g)的活产率从2001—2019年的8.18‰(7.21‰～9.29‰)降至2020年的2.17‰,下降倍数为3.77(1.21～11.75)(P=0.022)[38]。伊朗Ranjbar等[14]得到了类似的结论。
但也有研究结论与之相反,西班牙的一项国家性队列研究[39]报告:低出生体重和巨大儿的发生率均有所增加,乌拉圭Briozzo等[40]的单中心研究认为低出生体重(<2 500 g)的发生率(12%)高于2019年(9.8%)。而荟萃分析认为[15,28]疫情前后低出生体重(<2 500 g)、极低出生体重(<1 500 g)或极端低出生体重(<1 000 g)的发生率没有差异。因出生体重与妊娠期并发症关系密切,且影响因素非常复杂,需要后续更多的研究进一步讨论。
疫情对于死胎的影响也得到了广泛的研究,英国一项纳入疫情前1 718例分娩和疫情期间1 681例孕妇的单中心研究认为疫情期间死产的发生率显著增高,疫情期间为6.98 ‰,而疫情前为1.2‰[16],以色列的一家单中心研究也有一致的结果[19]。死胎率增加与围分娩期的焦虑、忽视胎动减少的情况以及产检次数减少有关[19,41-43]。但澳大利亚[44]一项纳入了三家医院孕产妇的队列研究认为,没有证据表明疫情后死胎率增加(0.7% vs.0.9%;RR=0.83,95%CI:0.48～1.44,P =0.515),Shah等[45]得到了类似的结论。一项基于32项研究、疫情期间797 416名孕产妇的荟萃分析[28]认为,疫情期间和疫情前的死胎风险没有显著差异。进一步的亚组分析显示,无论是单中心研究或是较大的区域/国家性研究中,死胎率均无显著差异。
相关的研究还发现,疫情期间胎膜早破的发生率明显增高(20.6% vs.11.0%,P <0.001)[46],与Du等[47]对北京地区7 699名孕妇的队列研究相似(调整后RR=1.11,95%CI:1.04～1.18; P<0.01),这可能与疫情后孕产妇的焦虑增加相关[48-49]。孕产妇的焦虑和抑郁会导致肌酐和胆碱水平下降以及皮质醇昼夜模式改变(表现为皮质醇下降扁平和夜间皮质醇升高),而这些都是胎膜早破的高危因素[50-51]。Du等[47]的研究还发现疫情前胎儿窘迫527例(11.7%),疫情后418例(13.1%),疫情期间胎儿窘迫的风险有所增加(调整后RR=1.14,95%CI:1.01～1.29;P=0.028),这可能与疫情期间分娩期的资源紧张有关。疫情期间为了利于术前的充分防护和准备,胎儿窘迫早期预警的标准有所放松,这也导致了胎儿窘迫诊断率的升高,但是否与压力引起的心理、神经内分泌和神经化学变化有关,尚无证据[26]。
新冠肺炎疫情期间,为了尽可能控制新冠病毒传播,许多国家采取一定的出行限制措施,这可能会增加孕妇的社会隔离压力[26]。一项研究报道,由于担心感染而被隔离,三分之一的妇女接受了不充分的产检,这可能导致围产期保健的指导不足,增加不良妊娠结局的风险[3,7]。疫情考虑到分娩医院及住院时间与孕产妇及新生儿健康显著相关[52-55],而对疫情的恐惧可能导致患者从救治水平较高的医院转诊到就近医院分娩,孕产妇由于对疫情的担忧而发生的就诊行为变化应得到注意[56]。
为减少疫情对妊娠健康的影响,国家卫生健康委员会于2020年2月8日发布新通知,建议加强对孕妇的健康咨询、筛查和随访[57]。此外,国内多家医院采取综合措施(如网上预约服务、网上会诊、门诊服务等),尽量减低新冠肺炎疫情对孕期及医疗服务的影响,确保孕产妇获得产前护理[5,47]。疫情期间,应将孕产妇这一敏感人群视为重点关注对象,确保及早发现和干预高危孕妇。为确保获得产前护理,医院应采取全面和个性化措施,在随访中尽可能多地评估和监测不良妊娠结局的风险[58]。此外,除基本的医疗服务外,还应教育孕妇在疫情期间定期产前检查、健康的生活方式和预防感染的措施(戴口罩、手部卫生等)的重要性。
综上所述,疫情对未感染孕妇围产结局的影响存在显著的报道偏倚,这可能源于单中心小样本和较大的区域性研究的差别,也可能与潜在的产检和转诊模式的改变有关,中国对未感染孕妇围产结局影响的研究仍然存在较大空白,需要进一步的研究探索疫情对于未感染孕妇的影响,为疫情期间孕产妇的管理提供参考和指导。
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