PDF(Pubmed)
Abstract：
BACKGROUND: Small-for-gestational-age (SGA), commonly caused by poor placentation, is a major contributor to global perinatal mortality and morbidity. Maternal serum levels of placental protein and angiogenic factors are changed in SGA. Using data from a population-based pregnancy cohort, we estimated the relationships between levels of second-trimester pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF), and serum soluble fms-like tyrosine kinase-1 (sFlt-1) with SGA.
METHODS: Three thousand pregnant women were enrolled. Trained health workers prospectively collected data at home visits. Maternal blood samples were collected, serum aliquots were prepared and stored at -80℃. Included in the analysis were 1,718 women who delivered a singleton live birth baby and provided a blood sample at 24-28 weeks of gestation. We used Mann-Whitney U test to examine differences of the median biomarker concentrations between SGA (< 10th centile birthweight for gestational age) and appropriate-for-gestational-age (AGA). We created biomarker concentration quartiles and estimated the risk ratios (RRs) and 95% confidence intervals (CIs) for SGA by quartiles separately for each biomarker. A modified Poisson regression was used to determine the association of the placental biomarkers with SGA, adjusting for potential confounders.
RESULTS: The median PlGF level was lower in SGA pregnancies (934 pg/mL, IQR 613-1411 pg/mL) than in the AGA (1050 pg/mL, IQR 679-1642 pg/mL; p < 0.001). The median sFlt-1/PlGF ratio was higher in SGA pregnancies (2.00, IQR 1.18-3.24) compared to AGA pregnancies (1.77, IQR 1.06-2.90; p = 0.006). In multivariate regression analysis, women in the lowest quartile of PAPP-A showed 25% higher risk of SGA (95% CI 1.09-1.44; p = 0.002). For PlGF, SGA risk was higher in women in the lowest (aRR 1.40, 95% CI 1.21-1.62; p < 0.001) and 2nd quartiles (aRR 1.30, 95% CI 1.12-1.51; p = 0.001). Women in the highest and 3rd quartiles of sFlt-1 were at reduced risk of SGA delivery (aRR 0.80, 95% CI 0.70-0.92; p = 0.002, and aRR 0.86, 95% CI 0.75-0.98; p = 0.028, respectively). Women in the highest quartile of sFlt-1/PlGF ratio showed 18% higher risk of SGA delivery (95% CI 1.02-1.36; p = 0.025).
CONCLUSIONS: This study provides evidence that PAPP-A, PlGF, and sFlt-1/PlGF ratio measurements may be useful second-trimester biomarkers for SGA.
METHODS: Three thousand pregnant women were enrolled. Trained health workers prospectively collected data at home visits. Maternal blood samples were collected, serum aliquots were prepared and stored at -80℃. Included in the analysis were 1,718 women who delivered a singleton live birth baby and provided a blood sample at 24-28 weeks of gestation. We used Mann-Whitney U test to examine differences of the median biomarker concentrations between SGA (< 10th centile birthweight for gestational age) and appropriate-for-gestational-age (AGA). We created biomarker concentration quartiles and estimated the risk ratios (RRs) and 95% confidence intervals (CIs) for SGA by quartiles separately for each biomarker. A modified Poisson regression was used to determine the association of the placental biomarkers with SGA, adjusting for potential confounders.
RESULTS: The median PlGF level was lower in SGA pregnancies (934 pg/mL, IQR 613-1411 pg/mL) than in the AGA (1050 pg/mL, IQR 679-1642 pg/mL; p < 0.001). The median sFlt-1/PlGF ratio was higher in SGA pregnancies (2.00, IQR 1.18-3.24) compared to AGA pregnancies (1.77, IQR 1.06-2.90; p = 0.006). In multivariate regression analysis, women in the lowest quartile of PAPP-A showed 25% higher risk of SGA (95% CI 1.09-1.44; p = 0.002). For PlGF, SGA risk was higher in women in the lowest (aRR 1.40, 95% CI 1.21-1.62; p < 0.001) and 2nd quartiles (aRR 1.30, 95% CI 1.12-1.51; p = 0.001). Women in the highest and 3rd quartiles of sFlt-1 were at reduced risk of SGA delivery (aRR 0.80, 95% CI 0.70-0.92; p = 0.002, and aRR 0.86, 95% CI 0.75-0.98; p = 0.028, respectively). Women in the highest quartile of sFlt-1/PlGF ratio showed 18% higher risk of SGA delivery (95% CI 1.02-1.36; p = 0.025).
CONCLUSIONS: This study provides evidence that PAPP-A, PlGF, and sFlt-1/PlGF ratio measurements may be useful second-trimester biomarkers for SGA.
摘要：
背景：小于胎龄（SGA），通常由胎盘不良引起，是全球围产期死亡率和发病率的主要原因。母体血清中胎盘蛋白和血管生成因子的水平在SGA中发生变化。使用来自基于人群的怀孕队列的数据，我们估计了中期妊娠相关血浆蛋白-A（PAPP-A）水平之间的关系，胎盘生长因子(PlGF),和血清可溶性fms样酪氨酸激酶-1（sFlt-1）与SGA。
方法：纳入三千名孕妇。训练有素的卫生工作者在家访中前瞻性地收集数据。收集了产妇的血样,制备血清等分试样并储存在-80℃。分析中包括1,718名妇女，她们分娩了单胎活产婴儿，并在妊娠24-28周时提供了血液样本。我们使用Mann-WhitneyU检验来检查SGA（小于胎龄的10分出生体重）和适合胎龄（AGA）之间的中位生物标志物浓度差异。我们创建了生物标志物浓度四分位数，并分别针对每种生物标志物通过四分位数估计了SGA的风险比（RR）和95％置信区间（CI）。改良的泊松回归用于确定胎盘生物标志物与SGA的关联，调整潜在的混杂因素。
结果：SGA妊娠中的PlGF中位数水平较低（934pg/mL，IQR613-1411pg/mL）比AGA（1050pg/mL，IQR679-1642pg/mL；p<0.001)。SGA妊娠的sFlt-1/PlGF比值中位数（2.00，IQR1.18-3.24）高于AGA妊娠（1.77，IQR1.06-2.90；p=0.006）。在多元回归分析中，PAPP-A最低四分位数的女性患SGA的风险高25%(95%CI1.09~1.44;p=0.002).对于PlGF，在最低的（aRR1.40，95％CI1.21-1.62;p<0.001）和第二四分位数（aRR1.30，95％CI1.12-1.51;p=0.001）的女性中，SGA风险较高。sFlt-1最高和第3四分位数的女性SGA分娩风险降低(分别为aRR0.80,95%CI0.70-0.92;p=0.002,和aRR0.86,95%CI0.75-0.98;p=0.028)。sFlt-1/PlGF比率最高四分位数的女性SGA分娩风险高18％（95％CI1.02-1.36；p=0.025）。
结论：这项研究提供了证据表明PAPP-A，PlGF,和sFlt-1/PlGF比值测量可能是SGA的中期妊娠生物标志物。
方法：纳入三千名孕妇。训练有素的卫生工作者在家访中前瞻性地收集数据。收集了产妇的血样,制备血清等分试样并储存在-80℃。分析中包括1,718名妇女，她们分娩了单胎活产婴儿，并在妊娠24-28周时提供了血液样本。我们使用Mann-WhitneyU检验来检查SGA（小于胎龄的10分出生体重）和适合胎龄（AGA）之间的中位生物标志物浓度差异。我们创建了生物标志物浓度四分位数，并分别针对每种生物标志物通过四分位数估计了SGA的风险比（RR）和95％置信区间（CI）。改良的泊松回归用于确定胎盘生物标志物与SGA的关联，调整潜在的混杂因素。
结果：SGA妊娠中的PlGF中位数水平较低（934pg/mL，IQR613-1411pg/mL）比AGA（1050pg/mL，IQR679-1642pg/mL；p<0.001)。SGA妊娠的sFlt-1/PlGF比值中位数（2.00，IQR1.18-3.24）高于AGA妊娠（1.77，IQR1.06-2.90；p=0.006）。在多元回归分析中，PAPP-A最低四分位数的女性患SGA的风险高25%(95%CI1.09~1.44;p=0.002).对于PlGF，在最低的（aRR1.40，95％CI1.21-1.62;p<0.001）和第二四分位数（aRR1.30，95％CI1.12-1.51;p=0.001）的女性中，SGA风险较高。sFlt-1最高和第3四分位数的女性SGA分娩风险降低(分别为aRR0.80,95%CI0.70-0.92;p=0.002,和aRR0.86,95%CI0.75-0.98;p=0.028)。sFlt-1/PlGF比率最高四分位数的女性SGA分娩风险高18％（95％CI1.02-1.36；p=0.025）。
结论：这项研究提供了证据表明PAPP-A，PlGF,和sFlt-1/PlGF比值测量可能是SGA的中期妊娠生物标志物。
