Genetics Program, North York General Hospital, 4001 Leslie Street, Toronto, ON, M2K 1E1, Canada.
Prenatal Screening Ontario, Better Outcomes Registry & Network (BORN) Ontario, Ottawa, ON, Canada.
BMC Pregnancy Childbirth. 2022 Mar 8;22(1):190. doi: 10.1186/s12884-022-04514-4.
Abnormal levels of maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE). The secondary aim was to assess this combination in identifying pregnancies at risk for gestational hypertension and preterm birth.
This case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE who delivered at < 37 and < 34 weeks of gestation, respectively.
There were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p < 0.0001), PlGF (0.76 vs 1.01, p < 0.0001) and free-β hCG (0.81 vs. 0.98, p < 0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p < 0.01) and PlGF (0.75 vs 1.02, p < 0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free β-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester. The corresponding DR was 58% for gestational hypertension and 36% for preterm birth cases.
Maternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy. This combination was less accurate in predicting women who have gestational hypertension or preterm birth.
多项标记物唐氏综合征筛查中母体生化标志物水平异常与不良妊娠结局有关。本研究旨在评估在第一和第二孕期中母体特征和生化标志物的组合是否可用于子痫前期（PE）的筛查。次要目的是评估这种组合在识别妊娠高血压和早产风险方面的作用。
本病例对照研究使用了接受多项标记物唐氏综合征筛查的孕妇的母体特征和残留血样信息。病例组（PE、妊娠高血压和早产孕妇）和对照组的中位数倍数（MoM）的第一和第二孕期生化标志物中位数进行了比较。生化标志物包括妊娠相关血浆蛋白 A（PAPP-A）、胎盘生长因子（PlGF）、人绒毛膜促性腺激素（hCG）、甲胎蛋白（AFP）、未结合雌三醇（uE3）和抑制素 A。使用不同的标志物组合进行逻辑回归分析来估计筛查性能。筛查性能定义为检出率（DR）和假阳性率（FPR）。早产和早发型子痫前期 PE 定义为在妊娠 37 周前和妊娠 34 周前分娩的 PE 孕妇。
有 147 例 PE（81 例足月，49 例早产，17 例早发型），295 例妊娠高血压和 166 例早产。与对照组相比，PE 病例在第一孕期的 PAPP-A（0.77 与 1.10，p<0.0001）、PlGF（0.76 与 1.01，p<0.0001）和游离β-hCG（0.81 与 0.98，p<0.001）的中位数 MoM 明显较低，同时在第二孕期的 PAPP-A（0.82 与 0.99，p<0.01）和 PlGF（0.75 与 1.02，p<0.0001）的中位数 MoM 也较低。早产和早发型 PE 的第一孕期 PAPP-A、PlGF 和游离β-hCG 最低。在 20%的 FPR 下，用第一孕期的母体特征和 PAPP-A、PlGF 联合预测，可预测 67%的早产和 76%的早发型 PE 病例。PE 病例的相应 DR 为 58%，而妊娠高血压和早产的病例分别为 36%和 58%。
为唐氏综合征筛查测量的第一孕期的母体特征和 PlGF 与生化标志物相结合，可合理准确地识别有发生早发型 PE 风险的妇女，从而对高危妇女进行分诊，以进一步进行调查和降低风险治疗。这种组合在预测妊娠高血压或早产妇女方面的准确性较低。
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