Objective

To assess perinatal outcomes of first pregnancy after remission from gestational trophoblastic neoplasia and the impact of the time between the end of chemotherapy and the subsequent pregnancy.

Data Sources

The Medical Subject Headings related to perinatal outcomes, chemotherapy, and gestational trophoblastic neoplasia were used alone or in combination to retrieve relevant articles. We searched all references registered until April, 2019 in Embase, LILACS, MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science.

Study Eligibility Criteria

We included any observational or interventional studies that evaluated perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia. Animal studies, narrative reviews, expert opinions, and previous treatments with potential risks for future perinatal outcomes which may introduce confounding bias were excluded.

Study Appraisal and Synthesis Methods

Two reviewers independently screened all identified references for eligibility and data extraction. Methodological quality and bias of included studies were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institutes of Health. For the meta-analysis, the measures of association were calculated using bivariate random-effects models. Statistical heterogeneity was evaluated with I² statistics and explored through sensitivity analysis. Publication bias was assessed by visual inspection of the funnel plot or Egger’s test, according to the number of articles included. For all analyses, a P value of <.05 indicated statistical significance. This study was registered on PROSPERO (CRD42018116513).

Results

A total of 763 studies were identified after literature search and 23 original studies were included in the systematic review and in the meta-analysis. The combined data from the subgroup meta-analysis (outcome vs time after chemotherapy) showed an incidence of spontaneous abortion of 15.28% (95% confidence interval, 12.37–18.74; I²=73%), 3.30% of malformation (95% confidence interval, 2.27–4.79; I²=31%), 6.19% of prematurity (95% confidence interval, 5.03–7.59; I²=0), and 1.73% of stillbirth (95% confidence interval, 1.17–2.55; I²=0%). These results were not influenced by the time between the end of chemotherapy and the subsequent pregnancy in most of the studied outcomes, including malformation (P=.14, I²=31%), prematurity (P=.46, I²=0), and stillbirth (P=.66, I²=0). However, there was a higher occurrence of spontaneous abortion (P<.01, I²=73%) in pregnancies that occurred ≤6 months after chemotherapy.

Conclusion

Chemotherapy for gestational trophoblastic neoplasia does not appear to increase the chance of unfavorable perinatal outcomes, except for the higher occurrence of spontaneous abortion in pregnancies occurring ≤6 months after chemotherapy.

中文翻译：

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妊娠滋养细胞肿瘤化疗后首次妊娠的围产期结局：观察性研究和荟萃分析的系统评价

客观的

评估妊娠滋养细胞肿瘤缓解后第一次妊娠的围产期结局以及化疗结束与随后妊娠之间时间的影响。

数据源

与围产期结局、化疗和妊娠滋养细胞肿瘤相关的医学主题词单独或组合使用以检索相关文章。我们检索了截至 2019 年 4 月在 Embase、LILACS、MEDLINE、Cochrane Central Register of Controlled Trials 和 Web of Science 中注册的所有参考文献。

学习资格标准

我们纳入了任何评估妊娠滋养细胞肿瘤化疗后首次妊娠围产期结局的观察性或介入性研究。排除了动物研究、叙述性评论、专家意见和对未来围产期结果有潜在风险的先前治疗，这些治疗可能会引入混杂偏倚。

研究评估和综合方法

两名审查员独立筛选了所有已确定的参考文献的资格和数据提取。使用美国国立卫生研究院的观察队列和横断面研究质量评估工具评估纳入研究的方法学质量和偏倚。对于荟萃分析，使用双变量随机效应模型计算关联度量。^{用I 2}统计量评估统计异质性，并通过敏感性分析进行探索。根据包含的文章数量，通过漏斗图或 Egger 检验的目测评估发表偏倚。对于所有分析，P值 <.05 表明具有统计学意义。该研究已在 PROSPERO (CRD42018116513) 上注册。

结果

文献检索后共确定了 763 项研究，其中 23 项原始研究被纳入系统评价和荟萃分析。来自亚组荟萃分析的综合数据（结果与化疗后的时间）显示自然流产的发生率为 15.28%（95% 置信区间，12.37-18.74；I ² =73%），畸形率为 3.30%（95% 置信度）间隔，2.27–4.79；I ² =31%)，6.19% 的早产（95% 置信区间，5.03–7.59；I ² =0）和 1.73% 的死产（95% 置信区间，1.17–2.55；I ² =0%）。在大多数研究结果（包括畸形）中，这些结果不受化疗结束和随后怀孕之间的时间的影响（P =.14，I² =31%）、早产（P =.46，I ² =0）和死产（P =.66，I ² =0）。然而，在化疗后≤6个月的妊娠中，自然流产的发生率较高（P <.01，I ² =73%）。

结论

妊娠滋养细胞肿瘤的化疗似乎不会增加不良围产期结局的机会，除了化疗后≤6个月的妊娠自然流产发生率较高。