Bühling K J, Mönnich J, Henrich W, Brauer M, Heinze T, Siebert G, Dudenhausen J W
Klinik für Geburtsmedizin, Charité Campus Virchow-Klinikum, Berlin.
Z Geburtshilfe Neonatol. 2004 Dec;208(6):226-31. doi: 10.1055/s-2004-835869.
Maternal hyperglycemia during gestational diabetes leads to fetal hyperinsulinemia, which is associated with increased perinatal morbidity and mortality. Amniotic fluid insulin levels are therefore considered by some researchers to be ideal parameters to use in diagnosing gestational diabetes and making decisions about correct therapy. There are various recommendations about determining gestational diabetes early in pregnancy (< 24 weeks) by measuring amniotic fluid insulin. This study tests this association -- taking additional risk factors into account -- in a group of pregnant women who had genetic indications requesting for amniocentesis (AC).
All pregnant women who came to our clinic for genetically-determined amniocentesis from April 10, 1995 - Jan. 31, 2000 and who were between 12 and 24 weeks were included in our study. After a sample of amniotic fluid was taken, the laboratory performed a competitive radio-immuno-assay to determine the insulin concentration. O'Sullivan's cut-off values were used in diagnosing gestational diabetes. Since not all pregnant woman in our clinic were screened for gestational diabetes, we gathered our data retrospectively by checking all birth records; these were available in our clinic's data archive.
A total of 483 pregnant women were included in our study. 22 (4.6 %) of them were classified as gestational diabetics. The average value for amniotic fluid insulin was 1.21 mU/L +/- 0.89. The insulin values for the entire study population exhibited a weekly increase of 0.1 mU/L from the 12th through the 24th week. The insulin concentrations for the 22 gestational diabetics were not significantly higher than those of the non-diabetics (1.05 mU/L vs. 1.0 mU/L; p = 0.34). In the 90 (th) percentile and above of the amniotic fluid insulin levels (2.2 mU/L) for the entire study population, the rate of gestational diabetics was at 11.8 % three times that of the non-diabetics, at 3.7 % (p = 0.021). Among the risk factors for gestational diabetes, an increased body mass index (BMI) value correlated significantly with increased insulin concentration (p < 0.001). The patients at and above the 90th percentile also had significantly higher BMI values (p = 0.002). In the multivariate analysis, the following influences were determined to be significant: maternal body mass index (p < 0.001) and the gestational age (p < 0,001), not the mere diagnosis of "gestational diabetes". A significant association was not found between elevated insulin values in amniotic fluid and the child's birth weight, APGAR values, pH-levels and blood glucose values. However, a significant association was found regarding fetal malformations and chromosome abnormalities.
Even very low concentrations of insulin can be identified in amniotic fluid early in the pregnancy. The values increase during the course of the pregnancy. There is a positive correlation between maternal weight (BMI) and insulin levels in the amniotic fluid. Pregnant women with gestational diabetes have higher insulin levels in their amniotic fluid. The multivariant analysis shows, however, that this association can be traced to the maternal BMI and the time point during the pregnancy when the AC was performed. Malformations, especially those with a neural tube defect, are an additional cause for elevated insulin values in amniotic fluid.
妊娠期糖尿病期间的母体高血糖会导致胎儿高胰岛素血症,这与围产期发病率和死亡率增加有关。因此,一些研究人员认为羊水胰岛素水平是诊断妊娠期糖尿病和做出正确治疗决策的理想参数。关于通过测量羊水胰岛素在妊娠早期(<24周)诊断妊娠期糖尿病有各种建议。本研究在一组有遗传指征要求进行羊膜穿刺术(AC)的孕妇中,考虑了其他风险因素,对这种关联进行了测试。
1995年4月10日至2000年1月31日期间到我们诊所进行基因测定羊膜穿刺术且孕周在12至24周之间的所有孕妇被纳入本研究。采集羊水样本后,实验室进行竞争性放射免疫测定以确定胰岛素浓度。使用奥沙利文的临界值诊断妊娠期糖尿病。由于我们诊所并非所有孕妇都进行了妊娠期糖尿病筛查,我们通过检查所有出生记录进行回顾性收集数据;这些记录可在我们诊所的数据档案中获取。
本研究共纳入483名孕妇。其中22名(4.6%)被归类为妊娠期糖尿病患者。羊水胰岛素的平均值为1.21 mU/L±0.89。整个研究人群的胰岛素值从第12周到第24周每周增加0.1 mU/L。22名妊娠期糖尿病患者的胰岛素浓度并不显著高于非糖尿病患者(1.05 mU/L对1.0 mU/L;p = 0.34)。在整个研究人群羊水胰岛素水平的第90百分位数及以上(2.2 mU/L),妊娠期糖尿病患者的比例为11.8%,是非糖尿病患者的三倍,为3.7%(p = 0.021)。在妊娠期糖尿病的风险因素中,体重指数(BMI)值升高与胰岛素浓度增加显著相关(p < 0.001)。处于第90百分位数及以上的患者BMI值也显著更高(p = 0.002)。在多变量分析中,确定以下影响因素具有显著性:母体体重指数(p < 0.001)和孕周(p < 0.001),而不仅仅是“妊娠期糖尿病”的诊断。未发现羊水胰岛素值升高与胎儿出生体重、阿氏评分、pH值和血糖值之间存在显著关联。然而,发现与胎儿畸形和染色体异常存在显著关联。
在妊娠早期羊水内就能检测到极低浓度的胰岛素。这些值在妊娠过程中会升高。母体体重(BMI)与羊水胰岛素水平之间存在正相关。妊娠期糖尿病孕妇的羊水胰岛素水平较高。然而,多变量分析表明,这种关联可追溯到母体BMI以及进行羊膜穿刺术时的妊娠时间点。畸形,尤其是神经管缺陷,是羊水胰岛素值升高的另一个原因。