Spong C Y, Ghidini A, Walker C N, Ossandon M, Pezzullo J C
Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Am J Obstet Gynecol. 1997 Nov;177(5):1085-7. doi: 10.1016/s0002-9378(97)70019-x.
Elevation of maternal serum alpha-fetoprotein in the second trimester is associated with poor pregnancy outcome, including fetal death, preterm delivery, and fetal growth restriction. We hypothesized that placental ischemia may be the common underlying pathogenesis of these outcomes. Thus we tested angiogenin, a potent inducer of neovascularization, in midtrimester amniotic fluid of patients with elevated maternal serum alpha-fetoprotein values to determine whether alpha-fetoprotein elevation is due to ischemia with subsequent stimulation of angiogenesis.
In this case-control study, patients with elevated maternal serum alpha-fetoprotein levels (> or = 2.0 multiples of the median, n = 9) at triple screen were matched with two controls (n = 18) on the basis of year of amniocentesis and maternal age, race, and parity. The median elevation of maternal serum alpha-fetoprotein in the study population was 4.01 multiples of the median (range 2.65 to 7.24 multiples of the median). Inclusion criteria were (1) singleton gestation, (2) no evidence of fetal structural or chromosomal anomalies, and (3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin (Quantikine, R&D Systems; sensitivity 0.026 ng/ml, interassay and intraassay coefficients of variation 4.6% and 2.9%, respectively). Statistical analysis included one-way analysis of variance and regression with p < 0.05 significant. Angiogenin and maternal serum alpha-fetoprotein values were normalized with use of natural log transformation for statistical analysis.
Angiogenin values were significantly elevated in patients with high maternal serum alpha-fetoprotein levels (median 31.1 [range 9.2 to 54.6] vs 17.1 [range 9.0 to 29.2] ng/ml, p = 0.02). Mean gestational age at sampling, maternal age, and year of amniocentesis were not significantly different between the study and control groups (each p > 0.05). As anticipated, there was a significant increase in preterm deliveries and small-for-gestational-age neonates in the patients with elevated maternal serum alpha-fetoprotein levels (each p < 0.01).
Midtrimester amniotic fluid angiogenin levels are significantly elevated in patients with elevated midtrimester maternal serum alpha-fetoprotein levels. Because angiogenin is a known marker of tissue ischemia, resulting in neovascularization, we hypothesize that elevation of maternal serum alpha-fetoprotein levels at triple screen is due to placental ischemia.
孕中期母体血清甲胎蛋白升高与不良妊娠结局相关，包括胎儿死亡、早产和胎儿生长受限。我们推测胎盘缺血可能是这些结局的共同潜在发病机制。因此，我们检测了血管生成素（一种强有力的新血管形成诱导剂）在母体血清甲胎蛋白值升高患者的孕中期羊水中的水平，以确定甲胎蛋白升高是否由于缺血继而刺激血管生成所致。
在这项病例对照研究中，三联筛查时母体血清甲胎蛋白水平升高（≥2.0倍中位数，n = 9）的患者，根据羊膜腔穿刺年份、母亲年龄、种族和产次与两名对照者（n = 18）进行匹配。研究人群中母体血清甲胎蛋白的中位数升高为4.01倍中位数（范围为2.65至7.24倍中位数）。纳入标准为：（1）单胎妊娠；（2）无胎儿结构或染色体异常证据；（3）遗传性羊膜腔穿刺。采用免疫分析法检测羊水中的血管生成素（Quantikine，R&D Systems公司；灵敏度为0.026 ng/ml，批间和批内变异系数分别为4.6%和2.9%）。统计分析包括单因素方差分析和回归分析，p < 0.05为有统计学意义。血管生成素和母体血清甲胎蛋白值采用自然对数转换进行标准化以进行统计分析。
母体血清甲胎蛋白水平高的患者血管生成素值显著升高（中位数31.1[范围9.2至54.6]对17.1[范围9.0至29.2] ng/ml，p = 0.02）。研究组和对照组在采样时的平均孕周、母亲年龄和羊膜腔穿刺年份方面无显著差异（p均> 0.05）。正如预期的那样，母体血清甲胎蛋白水平升高的患者中早产和小于胎龄儿显著增加（p均< 0.01）。
孕中期母体血清甲胎蛋白水平升高的患者，其孕中期羊水血管生成素水平显著升高。由于血管生成素是组织缺血导致新血管形成的已知标志物，我们推测三联筛查时母体血清甲胎蛋白水平升高是由于胎盘缺血所致。
