Neuroactive steroids including allopregnanolone are implicated in the pathophysiology of peripartum depressive symptoms (PDS). We performed a systematic review searching PubMed/Embase/PsychInfo/Cinhail through 08/2023 (updated in 07/2024), and conducted a random-effects meta-analysis of studies comparing allopregnanolone blood concentrations in women with versus without PDS at various timepoints during the 2^nd and 3^rd trimester and the postpartum period, calculating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Meta-regression and subgroup analyses included age, diagnoses of affective disorders before pregnancy, antidepressant treatment, analytical methods, and sample type. Study quality was assessed using the Newcastle-Ottawa-scale. The study protocol was registered on PROSPERO (registration number CRD42022354495). We retrieved 13 studies with 2509 women (n = 849 with PDS). Allopregnanolone concentrations did not differ between women with versus without PDS at any timepoint (p > 0.05). Allopregnanolone concentrations assessed during pregnancy did not differ for women with versus without PDS at postpartum follow-up (p > 0.05). Subgroup analyses indicated higher allopregnanolone concentrations in women with versus without PDS at gestational weeks 21–24 and 25–28 (SMD = 1.07, 95% CI = 0.04, 2.11 and SMD = 0.92, 95% CI = 0.26, 1.59 respectively). Moreover, we reported differences between studies using mass-spectrometry combined with chromatography versus immunoassays at gestational weeks 25–28 (p = 0.01) and plasma versus serum samples at gestational weeks 21–24 (p = 0.005). Study quality was rated as poor, good, and fair for two, one and ten studies respectively. PDS were not associated with differences for allopregnanolone concentrations. The use of heterogenous peripartum time points, study cohorts, depression symptom measures and analytical methods has hampered progress in elucidating neuroactive steroid signaling linked to PDS.

包括异孕酮在内的神经活性类固醇与围产期抑郁症状 （PDS） 的病理生理学有关。我们进行了系统评价，检索了 PubMed/Embase/PsychInfo/Cinhail 至 2023 年 8 月（2024 年 7 月更新），并对比较 PDS 女性在妊娠第 2 和第 3 个月以及产后不同时间点的异孕酮血药浓度的研究进行了随机效应荟萃分析，计算标准化均数差 （SMD） 和 95% 置信区间 （CIs）。Meta 回归和亚组分析包括年龄、怀孕前情感障碍的诊断、抗抑郁治疗、分析方法和样本类型。使用 Newcastle-Ottawa 量表评估研究质量。研究方案在 PROSPERO 上注册（注册号 CRD42022354495）。我们检索了 13 项研究，涉及 2509 名女性 （n = 849 名 PDS）。在所有时间点，患有 PDS 的女性与没有 PDS 的女性之间的异孕酮浓度没有差异 （p > 0.05）。在产后随访中，有 PDS 和无 PDS 的妇女在怀孕期间评估的 Allopregnanolone 浓度没有差异 （p > 0.05）。亚组分析显示，在妊娠 21-24 周和第 25-28 周，有 PDS 的妇女与无 PDS 的妇女的异孕酮浓度较高（分别为 SMD = 1.07、95% CI = 0.04、2.11 和 SMD = 0.92、95% CI = 0.26、1.59）。此外，我们报告了在妊娠 25-28 周 （p = 0.01） 使用质谱法结合色谱法与免疫测定法的研究与妊娠 21-24 周血浆与血清样本 （p = 0.005） 的研究之间的差异。两项、一项和十项研究的研究质量分别被评为差、良好和一般。 PDS 与异孕酮浓度的差异无关。异质性围产期时间点、研究队列、抑郁症状测量和分析方法的使用阻碍了阐明与 PDS 相关的神经活性类固醇信号传导的进展。