Data Sheet 1_Association of Placental Growth Factor with the risk of adverse pregnancy outcomes: a prospective cohort study in Chinese pregnant women.docx

BackgroundAdverse pregnancy outcomes, such as preterm birth, preeclampsia (PE), small for gestational age (SGA), pose significant risks to maternal and neonatal health and contribute to healthcare burdens. Placental Growth Factor (PIGF), a key pro-angiogenic biomarker involved in placental development, has been implicated in the pathophysiology of these complications. This study aimed to investigate the association between maternal serum PIGF levels and adverse pregnancy outcomes in a prospective cohort.
MethodsWe conducted a cohort study involving 5,870 women with singleton pregnancies enrolled at Nanjing Drum Tower Hospital from January 2017 to September 2020. Participants were followed from early pregnancy (≤14 gestational weeks) through delivery. Logistic regression models were used to evaluate the associations between serum PIGF levels (measured at 11–14 gestational weeks) and adverse pregnancy outcomes, reported as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Dose–response relationships were assessed using restricted cubic spline analysis.
ResultsSerum PIGF concentrations in early pregnancy were inversely associated with PE (OR = 0.97, 95% CI:0.96 – 0.98), preterm PE (OR = 0.96, 0.94 – 0.98), SGA <10th percentile (OR = 0.99, 0.98 – 0.99) and SGA <3rd percentile (OR = 0.98, 0.97 – 0.99). Expressed as multiples of the median (MoM), PIGF showed stronger associations with these outcomes, including PE (OR = 0.32, 0.21 – 0.48), preterm PE (OR = 0.23, 0.09 – 0.56), SGA <10th percentile (OR = 0.67, 0.54 – 0.83) and SGA <3rd percentile (OR = 0.43, 0.29 – 0.64), compared with its absolute concentrations. Notably, PIGF demonstrated a consistent inverse association with PE across different modes of conception, including spontaneous pregnancies (OR = 0.97, 0.96 – 0.98) and those conceived via ovulation induction or in vitro fertilization (OR = 0.95, 0.92 – 0.97). The highest predictive performance for PE was observed between 28–34 gestational weeks, with an area under the curve (AUC) of 0.79 (95% CI: 0.77 – 0.81). Additionally, dose–response analysis revealed nonlinear associations between PIGF levels and risks of SGA <10th and SGA <3rd.
ConclusionThis cohort study reinforces the inverse association between maternal PIGF levels and the risks of PE and SGA. The findings highlight the potential clinical utility of PIGF as a gestational age–specific biomarker in prenatal risk stratification.

背景：不良妊娠结局，如早产、子痫前期（preeclampsia, PE）、小于胎龄儿（small for gestational age, SGA），对孕产妇及新生儿健康构成严重威胁，并加剧医疗负担。胎盘生长因子（Placental Growth Factor, PIGF）是参与胎盘发育的关键促血管生成生物标志物，已被证实与上述并发症的病理生理过程相关。本研究旨在通过前瞻性队列研究，探讨孕妇血清PIGF水平与不良妊娠结局之间的关联。
方法：本研究开展了一项队列研究，纳入2017年1月至2020年9月期间在南京鼓楼医院登记的5870名单胎妊娠女性。研究对象从妊娠早期（≤14孕周）开始随访直至分娩。采用logistic回归模型评估妊娠11~14孕周时检测的血清PIGF水平与不良妊娠结局的关联，结果以校正后比值比（adjusted odds ratios, ORs）及95%置信区间（confidence intervals, CIs）报告。采用限制性立方样条分析评估剂量-反应关系。
结果：妊娠早期血清PIGF浓度与PE（OR = 0.97, 95% CI:0.96 – 0.98）、早发型子痫前期（OR = 0.96, 0.94 – 0.98）、SGA<10百分位数（OR = 0.99, 0.98 – 0.99）及SGA<3百分位数（OR = 0.98, 0.97 – 0.99）呈负相关。以中位数倍数（multiples of the median, MoM）表示PIGF水平时，其与上述结局的关联强度显著高于以绝对浓度表示的结果：PE（OR = 0.32, 0.21 – 0.48）、早发型子痫前期（OR = 0.23, 0.09 – 0.56）、SGA<10百分位数（OR = 0.67, 0.54 – 0.83）及SGA<3百分位数（OR = 0.43, 0.29 – 0.64）。值得注意的是，无论自然受孕（OR = 0.97, 0.96 – 0.98）还是通过促排卵或体外受精受孕（OR = 0.95, 0.92 – 0.97），PIGF水平与PE均呈现一致的负相关关系。针对PE的最高预测效能出现在妊娠28~34孕周，曲线下面积（area under the curve, AUC）为0.79（95% CI: 0.77 – 0.81）。此外，剂量-反应分析显示，PIGF水平与SGA<10百分位数及SGA<3百分位数的发病风险呈非线性关联。
结论：本队列研究证实，孕妇血清PIGF水平与PE及SGA的发病风险呈负相关。研究结果凸显了PIGF作为孕周特异性生物标志物在产前风险分层中的潜在临床应用价值。