Pregnant women who contract the H1N1 influenza virus are much more likely to develop severe disease than the general population, so they should receive antiviral treatment as soon as possible after symptoms appear – preferably within 48 hours.

These women who contract the virus are four times more likely to require hospitalization, and much more likely to die from it, according to a study in the July 29 online edition of The Lancet.

“If a pregnant woman feels like she may have influenza, she needs to call her health care provider right away,” said Dr. Denise J. Jamieson of the division of reproductive health at the Centers for Disease Control and Prevention’s National Center for Chronic Disease Prevention and Health Promotion in Atlanta, in a statement. “Clinicians who treat pregnant women should have a system in place for triaging pregnant women with influenza-like symptoms and they should not delay in initiating appropriate antiviral therapy. Some clinicians hesitate [to treat] pregnant women with antiviral medications because of concerns for the developing fetus, but this is the wrong approach. It is critical that pregnant women, in particular, be treated promptly.”

A total of 6 of the 45 H1N1 deaths that occurred from April 15 to June16 were in pregnant women – a rate of 13%, Dr. Jamieson, lead author of the study, and her colleagues wrote. But, since June 16 there have been an additional 257 H1N1 deaths in the United States, including an additional 9 pregnant women – bringing the total deaths to 302. “The Centers for Disease Control and Prevention has relatively complete information on 266 of these deaths,” Dr. Jamieson said in an interview. “Among them, 15 occurred in pregnant women, bringing the mortality rate closer to 6%.”

Although these numbers are small, they represent a large concern, she said. “Whether it’s 6% or 13%, it’s still a higher proportion of deaths than we would expect.”

The Lancet report provided detailed information on 34 confirmed or probable cases of H1N1 infection in pregnant women that were reported to the CDC from mid-April to mid-May. They ranged in age from 15-42 years; most (65%) were in their first or second trimester. Only 32% reported recent close contact with someone who had pneumonia or a flu-like illness, and only 12% reported recent travel to Mexico. Most women reported no epidemiologic link with the novel virus (Lancet 2009; doi:10.1016/S0140-6736[09]61304-0).

The most common presentation was a febrile, influenza-like illness (94% of the patients), which included fever plus cough or sore throat. Vomiting and diarrhea occurred in only 18% and 12%, respectively. “Generally, manifestations of pandemic H1N1 influenza virus were similar to those reported by the nonpregnant general population,” Dr. Jamieson and her colleagues wrote. “However, pregnant women were more likely to report shortness of breath compared with nonpregnant women of reproductive age (risk ratio 1.7) and with the nonpregnant general population (RR 2.3).”

The hospitalization rate among pregnant women with H1N1 was four times greater than that among the nonpregnant general population, the report noted (32% vs. 4%). All of the six women who died were healthy before the onset of influenza, but all developed a primary viral pneumonia and acute respiratory distress that required mechanical ventilation. Five of the patients underwent a cesarean section; all of the infants are alive and healthy. One woman, a 21-year-old at 11 weeks’ gestation, lost the fetus at the time of her death.

The cases seem to indicate a particular vulnerability in pregnant women to the novel virus. “We don’t know whether pregnant women are actually more susceptible to getting this virus, but we do know that if they do [become infected], they can be more severely affected,” Dr. Jamieson said in the interview. “There are mechanical, immunological, and hormonal changes in pregnancy that affect the cardiovascular and respiratory system – for instance, decreased lung capacity as the uterus expands – that make pregnant women more likely to develop severe disease.”

Another worrisome issue noted in the report was the delay in treatment that many women experienced. Only 50% of the cohort received oseltamivir, and only 24% began the treatment within 2 days of symptom onset, as recommended. The reasons are not entirely clear, but probably have to do with reluctance on the part of both the health care provider and the patient to use antivirals.

“I can only speculate that there is a hesitance to prescribe these drugs due to concerns about the developing fetus,” Dr. Jamieson said. “But the benefits of antiviral therapy very likely outweigh the risks, and we are recommending that pregnant women with suspected H1N1 influenza receive these drugs promptly.”

Although antivirals have not been thoroughly studied in pregnant women, the consensus is that the risk of untreated H1N1 infection is greater for both mother and fetus than any risks of the drug. “We know that pregnant women with influenza are more likely to have preterm births and fetal losses, and we know that untreated fever increases the risk of central nervous system defects in the fetus,” Dr. Jamieson said. “More significant in terms of the risk/benefit ratio is the fact that we know these women can get really sick, really fast, and that the baby won’t do well if the mom doesn’t.”

Current CDC guidelines for pregnant women recommend empiric treatment with antivirals as soon as possible after the onset of influenza symptoms, preferably within 48 hours. Treatment should proceed without waiting for lab results to confirm the influenza strain, the guidelines state. The drug of choice is oseltamivir, at a dosage of 75 mg twice per day for 5 days ( www.cdc.gov/h1n1flu/clinician_pregnant.htm).

Dr. Jamieson could not offer advice on vaccination strategies, should a vaccine become available this fall. The CDC’s Advisory Committee on Immunization Practices will tackle that issue during a meeting scheduled for July 29 to formalize its recommendations.

“I would suspect that pregnant women will be one of the groups considered as high priority for vaccination,” Dr. Jamieson said.

This study was funded by the CDC. The researcher, including members of the Novel Influenza A (H1N1) Pregnancy Working Group, had no financial conflicts of interest related to this study.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

接触H1N1流感病毒的孕妇较普通人更可能发展成重症疾病，因此一旦她们出现症状，应尽快，最好在48 h以内，接受抗病毒药物治疗。

 

表现出H1N1流感症状的孕妇应在症状出现48 h内接受治疗

 

根据7月29日《柳叶刀》（The Lancet）在线版刊出的一项研究结果，接触该病毒的孕妇较普通人需入院治疗的可能性增加4倍，也更可能因病致死。

 

就职于亚特兰大美国疾控中心所属国家慢性病预防和健康促进中心生殖健康部门的Denise J. Jamieson医生在声明中指出：“孕妇如感到可能患上流感，应马上通知其卫生保健医生。保健医生应采用适当的系统以筛选出具有流感样症状的孕妇并尽快对其进行相应的抗病毒药物治疗。考虑到药物对胚胎发育的可能影响，有些医生对应用抗病毒药物治疗孕妇感到犹豫，但这是错误的。特别是对孕妇，尽早进行治疗是很关键的。”

 

此项研究的领导者Jamieson医生及其同事提出，从4月15日～6月16日间美国45名因感染H1N1流感病毒死亡病例中有6名为孕妇，占13%。但自6月16日美国另有257名死亡病例，包括9名孕妇，使得死亡病例总数达到302名。Jamieson 医生在综述中指出：“疾控中心已收集以上病例中266名死亡病例的相关信息，其中15名为孕妇，令病死率接近6%。”

她指出，虽然这一数据看似很小，但引起很大关注。“不管是6%还是13%，这一死亡比例仍比我们期望的高。”

 

《柳叶刀》上的报道提供了疾控中心4月中旬到5月中旬报告的34名确诊或疑似感染H1N1病毒孕妇的详细资料。她们的年龄在15～42岁之间，多数（65%）发生在孕早期或孕中期。仅32%的人报告近期密切接触过肺炎或有流感样病变的患者，仅12%的人称近期去过墨西哥旅行。多数孕妇没有与新型病毒接触的流行病学证据（参见Lancet 2009; doi:10.1016/S0140-6736[09]61304-0）。

 

患者最常见的表现（94%的患者）是发热以及包括发热加咳嗽或咽痛在内的流感样病变。呕吐和腹泻的发生率仅分别为18%和12%。Jamieson医生和她的同事写道：“总之，孕妇感染H1N1流感病毒的表现与非怀孕总人口相似。但与非怀孕的育龄妇女及非怀孕的总人口相比更可能出现气促，危险比分别为1.7和2.3。”

 

文中强调，感染H1N1病毒的孕妇的入院治疗率较非怀孕的总人口增加4倍（32%比 4%）。所有6名因病致死的孕妇流感发作前均健康，但都发展成原发性病毒性肺炎和急性呼吸窘迫，且需要机械通气。其中5名患者接受了剖宫产，所有婴儿存活并健康。一位21岁怀孕11周的孕妇和其腹中胎儿同时死亡。

 

这些病例显示孕妇在这种新型病毒面前显得特别脆弱。Jamieson医生在其综述中指出：“我们实际上并不清楚孕妇是否更易感染此病毒，但我们知道一旦感染了，她们受到的影响更为严重。由于怀孕引起机体的力学、免疫学以及激素水平的变化，造成心血管和呼吸系统受到不同程度的影响，如子宫扩大引起肺容量减小，均导致孕妇更有可能发展成重症疾病。”

 

文中提到的另一个惹人烦恼的问题是很多孕妇延迟了治疗。该组病例中仅50%的患者接受了奥塞米韦治疗，仅24%的患者按照建议在出现症状2 天内开始接受治疗。出现上述情况的原因尚不完全清楚，但医患双方均有部分人不愿使用抗病毒药物。

 

Jamieson医生认为：“我只能假设医生对开出这些药物产生犹豫的原因是关注胎儿的发育，但抗病毒治疗带来的益处很可能胜过其危险性。我们建议怀疑患有H1N1流感的孕妇应尽快使用抗病毒药物治疗。”

 

虽然尚未对孕妇应用抗病毒治疗进行彻底研究，但感染H1N1流感病毒而不治疗的危险性比抗病毒药物的对母亲和胎儿的任何危险性都大的多，这一点已是大家的共识。Jamieson医生提出：“我们知道，患有流感的孕妇更可能出现早产和妊娠丢失。我们还清楚，孕妇发热而不进行治疗会导致胎儿发生中枢神经系统缺陷的危险性增加。通过风险/效益比我们更能明确这样的事实，即孕妇确实患病，疾病进展确实迅速，如果母亲患病，那么婴儿也无法幸免。”

 

最近疾控中心在对孕妇的诊疗指南中建议，一旦出现流感症状，应尽快，最好在48 h内，采用经验疗法对孕妇进行抗病毒药物治疗。该指南声称，治疗无需等待实验室确认病毒株的结果。选用的药物为奥塞米韦，剂量为74 mg，每日两次，共用5 天（参见www.cdc.gov/h1n1flu/clinician_pregnant.htm）。

 

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