Lamont Ronnie F
Department of Obstetrics and Gynaecology, Imperial College London, Northwick Park and St Mark's Hospital/NHS Trust, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
BJOG. 2005 Mar;112 Suppl 1:67-73. doi: 10.1111/j.1471-0528.2005.00589.x.
Studies using different diagnostic methods and outcome parameters have used different antibiotics and dose/administration regimes to women of differing risk of preterm birth with, not surprisingly, different results. Studies which have shown benefit have been criticised for having either poor methodology, low sample size or having only showed benefit after a non-prespecified subgroup analysis. Studies which have failed to show any benefit have been criticised for unacceptable methods of diagnosing abnormal genital tract flora or having excluded a large percentage of patients eligible for the study, for having permitted a long period to elapse from diagnosis of abnormal genital tract flora to administration of treatment and for having employed treatment too late in pregnancy. A Cochrane Systematic Review of these studies failed to provide a definitive answer because this was published one month before two randomised double-blind placebo-controlled trials were published, in which clindamycin used either systemically or intravaginally in low risk, unselected women resulted in a 60% reduction in the incidence of preterm birth. This would have influenced the inconclusive results of the Cochrane review, with respect to general population studies. Very early spontaneous preterm labour and preterm birth is more likely to be of infectious aetiology than preterm birth just before term. The earlier in pregnancy at which abnormal genital tract flora is detected, the greater is the risk of an adverse outcome. Women with abnormal flora in early pregnancy, who subsequently revert to normal, continue to have a high risk of adverse outcome of pregnancy, at a degree similar to women with abnormal genital tract flora in early pregnancy who were treated with placebo. This suggests that whatever damage abnormal flora induces, this is at an early gestation, even if the flora subsequently reverts to normal. It follows therefore that if antibiotics are to be of help in preventing spontaneous preterm labour and preterm birth of infectious aetiology, these must be administered early in pregnancy. Antibiotics used prophylactically for the prevention of preterm birth are more likely to be successful if: they are used in women with abnormal genital tract flora (rather than other risk factors for preterm birth, e.g. low BMI, twins, generic previous preterm birth); they are used early in pregnancy prior to infection (tissue penetration/inflammation and tissue damage); they are used in women with the greatest degree of abnormal genital tract flora; and if they are used in women with a predisposition to mount a damaging inflammatory response to infection.
使用不同诊断方法和结果参数的研究，针对早产风险不同的女性使用了不同的抗生素及剂量/给药方案，结果自然也各不相同。那些显示出有益效果的研究受到了批评，原因要么是方法不佳、样本量小，要么是仅在非预先指定的亚组分析后才显示出有益效果。那些未能显示出任何益处的研究也受到了批评，其原因包括诊断异常生殖道菌群的方法不可接受、排除了很大比例符合研究条件的患者、从诊断异常生殖道菌群到开始治疗的时间间隔过长，以及在孕期过晚才采用治疗措施。对这些研究进行的一项Cochrane系统评价未能给出明确答案，因为该评价在两项随机双盲安慰剂对照试验发表前一个月发布，在这两项试验中，对低风险、未经过筛选的女性全身或经阴道使用克林霉素，使早产发生率降低了60%。这会影响Cochrane评价在一般人群研究方面得出的不确定结果。极早期自然早产比足月前早产更可能由感染病因引起。在孕期越早检测到异常生殖道菌群，不良结局的风险就越大。孕早期菌群异常但随后恢复正常的女性，其妊娠不良结局的风险仍然很高，程度与接受安慰剂治疗的孕早期生殖道菌群异常女性相似。这表明，无论异常菌群会引发何种损害，都是在妊娠早期发生的，即使菌群随后恢复正常。因此可以推断，如果抗生素要有助于预防感染病因导致的自然早产和早产，就必须在孕期早期给药。预防性使用抗生素来预防早产，如果满足以下条件则更有可能成功：用于生殖道菌群异常的女性（而非早产的其他风险因素，如低体重指数、双胞胎、既往有早产史）；在感染（组织穿透/炎症和组织损伤）之前的孕期早期使用；用于生殖道菌群异常程度最大的女性；以及用于对感染易产生有害炎症反应倾向的女性。
