Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China.
National Research Institute for Family Planning, Beijing, China.
Hum Reprod. 2024 Feb 1;39(2):326-334. doi: 10.1093/humrep/dead261.
Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)?
PPLs and their subsets are associated with the risk of SAB.
Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception.
STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship.
Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05).
LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined.
PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB.
STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests.
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妊娠前外周血白细胞（PPL）及其亚群是否会影响自然流产（SAB）的风险？
PPL 及其亚群与 SAB 的风险相关。
有说服力的研究表明，母体外周白细胞在胚胎着床和妊娠维持中起着至关重要的作用。受孕后，PPL 及其亚群会做出适应性变化。
研究设计、规模、持续时间：本基于人群的回顾性队列研究基于中国大陆国家免费孕前检查计划（NFPCP）的数据。计划在未来六个月内怀孕的夫妇可以获得免费的孕前健康检查和生殖健康咨询服务。本研究基于 2016 年怀孕的 1310494 名年龄在 20-49 岁的 NFPCP 女性参与者。在连续排除了 235456 名失访、多胎和未完成血液检查的参与者后，共有 1075038 名参与者被纳入主要分析。
参与者/材料、设置、方法：测量 PPL 及其亚群的计数和比例。主要结局是 SAB。多变量逻辑回归模型用于估计与 PPL 及其亚群相关的 SAB 的优势比（OR）和 95%置信区间（CI），并使用限制立方样条（RCS）估计非线性暴露-反应关系。
在所纳入的妊娠参与者中，共记录了 35529 例 SAB 事件（3.30%）。与 PPL 参考值的参与者相比，白细胞减少症和白细胞增多症的 SAB 的 OR（95%CI）分别为 1.14（1.09-1.20）和 0.74（0.69-0.79）。RCS 结果显示出单调下降趋势（P<0.05）。类似的关系也见于中性粒细胞计数和比例、单核细胞计数、中细胞计数和比例。淋巴细胞比例与 SAB 的风险呈正相关且呈非线性关系（P<0.05）。嗜酸性粒细胞和嗜碱性粒细胞与 SAB 的风险呈正相关（嗜酸性粒细胞 P<0.05，嗜碱性粒细胞 P<0.05）。
局限性、谨慎的原因：随访时未收集化学流产事件和 SAB 的原因。在受孕期间，准备怀孕和发展可行的 PPL 刺激方法的女性的 PPL 是否已经恢复，尚未确定。
PPL 及其亚群与 SAB 的风险相关。应重视在准备怀孕的女性中进行白细胞减少症和中性粒细胞减少症筛查，并制定可行的 PPL 刺激方法，以利用免疫机会窗口预防 SAB。
研究资金/利益冲突：本研究得到了国家卫生健康委员会国家重点研发计划（项目编号：2021YFC2700705[Y.Y.]和 2016YFC100307[X.M.]）和国家自然科学基金（项目编号：82003472[L.W.]）的支持。资金来源方未参与研究设计、数据收集、数据分析和解释、撰写报告或决定提交本文供发表。无利益冲突。
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