Insulin levels in amniotic fluid of normal and abnormal pregnancies

The normal level of insulin in amniotic fluid between the 13th and 42nd weeks of pregnancy was determined by means of 988 single analyses in individual healthy women. Insulin passes into the amniotic fluid via the fetal urine, and its level does not depend on fetal gender. Between the 13th and 25th weeks of gestation, the insulin level increases by an average of 1.3 to 5.1 microU/ml. From the 27th to the 42nd weeks, an increase of 6 to 9.1 microU/ml is observed. In the same period, the 97th percentile rises from 11.2 to 18 microU/ml. In 543 patients with pregnancy disorders, lower levels of insulin in amniotic fluid were observed in intrauterine fetal death, placental insufficiency, fetal growth retardation, and malformations. Elevated levels of insulin were observed in rhesus disease. In the treatment of pregnant women with betamimetics and glucocorticoids, the mean amniotic fluid insulin level rose to more than double the normal values.     

Glycosylated hemoglobin level in the second trimester predicts birth weight and amniotic fluid volume in non-diabetic pregnancies with abnormal screening test

Objective.?To investigate relationship between glycemic control in first half of pregnancy by measuring mid-pregnancy HbA1c and neonatal birth weight and amniotic fluid volume.

Methods.?We prospectively enrolled 220 pregnant women who received oral glucose tolerance test (OGTT) after positive gestational diabetes mellitus screening. We included 102 women with normal OGTT results into final analysis. We measured birth weight and amniotic fluid index (AFI) at 32–34 weeks.

Results.?Mean birth weight was 3313?±?426?g, and 15.7% of neonates were classified as large-for-gestational age (LGA). Mean Hb1Ac was 4.96?±?0.28%. Median AFI was 145?mm, and polyhydramnios rate was 2.9%. Birth weight was positively correlated with HbA1c level (r?=?0.373, p?<?0.001) and pre-pregnancy body mass index (BMI; r?=?0.351, p?<?0.001). Linear regression analysis showed that HbA1c and pre-pregnancy BMI were positive independent determinants of neonatal birth weight, and HbA1c was positive independent determinant of AFI. Receiver operating characeristics curve identified HbA1c level of 4.99 as optimal threshold for prediction of LGA with 93.8% sensitivity, 61.6% specificity and positive likelihood ratio (+LR) of 2.45 and pre-pregnancy BMI value of 25.2 as optimal threshold for prediction of LGA with 81.3% sensitivity, 57% specificity and +LR of 1.9.

Conclusion.?In non-diabetic pregnant women with abnormal screening test, mid-pregnancy HbA1c level and pre-pregnacy BMI may predict neonatal birth weight. AFI in 32–34 weeks of gestation is related with mid-pregnacy HbA1c level.     

羊水乳酸水平对羊水粪染病例胎儿窘迫的诊断价值

目的探讨羊水乳酸水平在羊水粪染病例中诊断胎儿窘迫的临床价值。方法2003年8月至2004年12月暨南大学第二临床医学院测定72例第一产程活跃期出现羊水粪染(观察组)和52例羊水清、胎儿监护图形正常且有良好新生儿结局(对照组)的羊水及新生儿脐动脉血乳酸水平。结果对照组羊水乳酸值近似正态分布,其95%参考值为5.4~8.9mmol/L。对照组活跃期和分娩时羊水乳酸水平差异无显著性意义(P>0.05)。羊水Ⅲ度粪染的羊水乳酸水平明显高于对照组(P<0.01)。羊水Ⅰ度及Ⅱ度粪染而胎儿监护正常的病例羊水乳酸值与对照组比较,差异无显著性意义(P>0.05)。但羊水Ⅱ度粪染合并胎心基线异常或(和)重度变异减速病例的羊水乳酸水平明显升高(P<0.01)。观察组发生胎儿窘迫及新生儿窒息的病例,其活跃期羊水乳酸水平均明显高于对照组(P<0.01)。以活跃期羊水乳酸值>8.9mmol/L为异常值来诊断胎儿窘迫发生的敏感性、特异性、阳性预测值及阴性预测值分别为61.9%、88.2%、68.4%和84.9%。结论羊水乳酸值测定对提高羊水粪染病例胎儿窘迫的诊断准确性有一定临床价值。     

Human amniotic fluid stem cells have better potential in early second trimester of pregnancy and can be reprogramed to iPS

Objective

To study the difference of amniotic fluid stem cell potential at different gestational age.

Interleukin-6 levels in umbilical artery serum in normal and abnormal pregnancies.

OBJECTIVE: The aim of our study was to determine the correlation of abnormal umbilical artery interleukin-6 levels with pregnancies complicated by preterm delivery and pre-eclampsia. METHOD: Cord serum (umbilical artery) was collected at delivery by cesarean section or spontaneous delivery. Samples were retrieved from patients with normal and abnormal pregnancies. Patients were divided into three groups: group 1, a control group of samples from uncomplicated pregnancies (n = 24); group 2, patients with pre-eclampsia (n = 21); and group 3, patients having had preterm delivery (n = 29). Interleukin-6 was measured by bioassays. Statistics were performed with the Mann-Whitney U-, Student's t- and the Kruskal-Wallis tests. RESULTS: Interleukin-6 levels in women with preterm delivery were statistically higher compared to those of normal pregnancies (P < 0.05) and lower in the cord serum of pre-eclamptic when compared to those of normal pregnancies (P < 0.05). CONCLUSION: In conclusion, we believe that further investigations could elucidate the role of this pleiotropic cytokine in both, normal and pathologic reproductive biology, and determine the clinical utility of IL-6 measurements in obstetric practice.     

High interleukin-16 concentrations in the early second trimester amniotic fluid: an independent predictive marker for preterm birth

Objective: Infection is believed to be one of frequent and important causes of preterm labor. We attempted to evaluate whether the level of inflammatory markers, e.g. interleukin-16 (IL-16), interleukin-18 (IL-18), and ferritin, in amniotic fluid at early second trimester can predict preterm birth. Methods: Amniotic fluid (AF) samples were collected from 350 pregnant women who had trans-abdominal amniocentesis for genetic indications at 16 to 20 weeks of gestation. AF levels of IL-16, IL-18 and ferritin levels were measured by immunoassay and were correlated with pregnancy outcomes. Results: Among the 350 pregnant women, 58 (16.6%) had preterm birth (<37 weeks gestation). AF levels of IL-16, IL-18, and ferritin were significantly higher in pregnant women with subsequent preterm birth. Multivariate analyses showed that a quartile higher of AF IL-16 level was significantly associated with preterm birth (OR: 3.09, 95% CI 1.52–6.27, p = 0.002). A receiver operating characteristic analysis revealed that an IL-16 cutoff value of 105 pg/ml was a reliable predictor of preterm birth (sensitivity, 90.2%; specificity, 52.7%; negative predictive value, 84.3%). Conclusion: It is feasible to predict preterm birth by measuring the AF levels of IL-16 especially for the pregnant women requiring genetic amniocentesis during early second trimester.     

正常妊娠晚期羊水中饱和卵磷脂的测定及药物影响

用改良的Ｔｓａｉ法测定了５０例（１００份）晚期妊娠及２１例临产妇女羊水中饱和卵磷脂（ＳＰＣ）的含量，得出不同孕周羊水中ＳＰＣ的正常值，并通过应用地塞米松和氨茶碱治疗前后，测定了羊水中ＳＰＣ的变化，认为用地塞米松后ＳＰＣ位增加明显，但氨茶碱可用于糖皮质激素应用禁忌者。     

Second trimester amniotic fluid endothelin-1 concentrations and subsequent development of intrauterine growth restriction

OBJECTIVE: The purpose of this prospective study was to record endothelin-1 (ET-1) concentrations in the second trimester amniotic fluid and compare these values in women who developed intrauterine growth restriction (IUGR) later in pregnancy with those with uneventful pregnancies. METHOD: Amniotic fluid was retrieved by amniocentesis from 125 women in the second trimester of pregnancy. The levels of ET1 were measured by a sensitive and specific radioimmunoassay. RESULTS: From the 125 women included in the study 12 had pregnancies that later developed IUGR and 88 had uneventful pregnancies. The ET1 concentration was significantly higher (P<0.005) in women who later developed IUGR than in normal pregnancy (106 pg/ml versus 64.7 pg/ml). CONCLUSION: The amniotic fluid concentration of ET1 is elevated by the second trimester in women who later develop IUGR.     

Alpha-fetoprotein content of amniotic fluid in normal and abnormal pregnancies.

Elevation above the normal range of alpha-fetoprotein (AFP) concentration in amniotic fluid occurs in the presence of certain fetal anomalies. The value of a new method for radioimmunoassay of APF in amniotic fluid was tested by an analysis of 486 samples taken by amniocentesis at various stages of pregnancy. The normal range of concentrations during pregnancy was established by 348 samples from healthy women with normal pregnancies. This was compared with the levels found in the presence of various fetal malformations--Rh-isoimmunization, maternal diabetes, chromosomal anomalies, and fetal death in utero. The findings and their implications are discussed.     

检测脐血及羊水中儿茶酚胺水平诊断胎儿窘迫

应用高效液相色谱技术，对足月正常分娩儿（１１例）、胎儿窘迫儿（３０例）的脐动脉血浆、及足月后羊水（３６例）中儿茶酚胺水平进行测定。结果表明：胎儿窘迫时，儿茶酚胺水平增高，以去甲肾上腺素（ＮＥ）、肾上腺素（Ｅ）为主，其增高的程度与新生儿窒息发生有关，并与Ａｐｇａｒ评分呈负相关。相关系数分别为ｒ＿（ＮＥ）＝－０．６３９（Ｐ＜０．０１），ｒ＿Ｅ＝－０．４５９（Ｐ＜０．０５）。儿茶酚胺增加是胎儿缺氧的早期表现。因此，监测胎儿儿茶酚胺水平，可作为早期诊断胎儿窘迫的一个指标。     

Sexual dimorphism in the levels of amniotic fluid leptin in pregnancies at 16 weeks of gestation: relation to fetal growth

OBJECTIVE: To investigate whether in the first half of pregnancy levels of leptin in amniotic fluid are sexually dimorphic, and are related to fetal growth. STUDY DESIGN: Samples of amniotic fluid were collected during amniocentesis from 211 pregnancies with a single fetus with a normal karyotype (107 from male fetuses). Fetal growth was evaluated at 16 and 32 weeks of gestation, by sonography, and in a subset of 137 women at delivery. RESULTS: Amniotic fluid leptin was significantly lower in male than female fetuses (7.91+/-0.36 ng/ml versus 10.45+/-0.38 ng/ml; p = 0.0001). In females, levels of leptin were inversely related to BPD measured at 16 weeks (r = -0.241; p = 0.013) to biparietal diameter (BPD) (r = -0.281; p = 0.0076) and abdominal circumference (r = 0.268; p = 0.0107) measured at 32 weeks of gestation and to neonatal weight (r = -0.236; p = 0.051), neonatal weight/height (r = -0.271; p = 0.026) or neonatal Kaup index (r = 0.255; p = 0.045). Leptin was not related to any fetal parameter in males. CONCLUSIONS: Levels of leptin in amniotic fluid at 16 weeks of gestation are sexually dimorphic and are inversely related to fetal growth, particularly of females.     

Alpha-fetoprotein concentration in amniotic fluid during the last trimester in normal pregnancies and in pregnancies with severe fetal abnormalities.

The concentration of alpha-fetoprotein (AFP) in the amniotic fluid was studied during the last trimester of pregnancy. 129 samples of amniotic fluid were collected by transabdominal amniocentesis in 94 pregnant women. Only women with uncomplicated pregnancies giving birth to normal infants at term were included. The 90% reference interval was calculated and a distinct decrease in the amniotic fluid AFP concentration was found during the last trimester. An AFP concentration above the 90% reference interval was found in 8 out of 10 cases of anencephaly. Normal AFP concentration was found in a case of congenital heart disease with severe oedema, and a low concentration was found in a case of Down's syndrome (Trisomy 21).     

Immunosuppressive activity of human amniotic fluid of normal and abnormal pregnancies

Twenty specimens of amniotic fluid (AF) obtained between week 16 and 18 of gestation from normal pregnant women and six specimens from pregnant women in which trisomia of chromosome 21 was found were tested for immunosuppressive activity. Incubation of normal human donor lymphocytes with 0.2-1 mL of AF from normal pregnant women for one hour at 37 degrees C was sufficient for induction of significant inhibition of the ability of these cells to induce a local xenogeneic graft-versus-host reaction (GVHR) as well as inhibition of E and E-active rosette formation, the GVHR being the most sensitive test. On the other hand, amniotic fluid obtained from the six pregnant women in which trisomia of chromosome 21 was found showed no inhibitory activity in either the E or E-active rosette formation, nor in the local xenogeneic graft-versus-host reaction. AF from all the women tested was found to have no effect on phenotype expression of the lymphocytes, as tested by the monoclonal antibodies OKT4+ and OKT8+, nor on B-lymphocytes, as tested by surface immunoglobulins. No correlation was found between the alpha-fetoprotein levels in the sera of those women and the immunosuppressive activity. These findings indicate that genetic defects of the conceptus are not limited to the embryo but may affect the composition of immunosuppressive components present in normal amniotic fluid.     

The amniotic fluid index, single deepest pocket, and two-diameter pocket in normal human pregnancy

OBJECTIVE: This study was undertaken to determine normative values for amniotic fluid index, single deepest pocket, and 2-diameter pocket across gestation. STUDY DESIGN: Fifty patients with normal pregnancies at each gestational age between 14 and 41 weeks' gestation were recruited prospectively and scanned once. Data were transformed into logarithmic (base 10) values for analysis. Polynomial regression equations were used to predict the normal values for amniotic fluid index, single deepest pocket, and 2-diameter pocket across gestational age and to predict the weekly percentage changes. RESULTS: The mean amniotic fluid index, single deepest pocket, and 2-diameter pocket values were significantly lower among patients at <37 weeks' gestation (n = 1150) than among those at > or =37 weeks' gestation (n = 250; P <.001 for all comparisons). The calculated prevalences of oligohydramnios (amniotic fluid index < or =5 cm, single deepest pocket <2 cm, or 2-diameter pocket <15 cm(2)) were significantly different (P <.0001) for the three techniques (8%, 1%, and 30%, respectively). Hydramnios (amniotic fluid index >24 cm, single deepest pocket >8 cm, or 2-diameter pocket >50 cm(2)) was also diagnosed with significantly different (P <.0001) frequencies (0%, 0.7%, and 3%, respectively). CONCLUSIONS: This is the largest prospective study to date to provide normative data for each of three ultrasonographic techniques used to assess amniotic fluid volume. The single deepest pocket appears to be the preferable method, because its use is least likely to lead to the false-positive diagnosis of either oligohydramnios or hydramnios.     

孕中期羊水细胞染色体核型分析及其异常核型发生率的比较

目的：分析孕中期羊水细胞染色体核型及比较不同异常核型的发生率,并对各种异常核型的临床意义进行探讨。方法1998年9月至2010年11月在复旦大学附属妇产科医院集爱遗传与不育诊疗中心行羊水细胞染色体检查的孕妇共13 648例,抽取并培养成功的羊水标本共计13 795份,即13 795个胎儿获得核型诊断,对上述胎儿根据其母亲（孕妇）不同检查指征进行分组：当孕妇年龄≥35岁时为高龄孕妇组（4065个）;血清学筛查提示高危时为血清筛查高危组（6462个）;超声筛查出现异常征象时为超声异常征象组（1539个）;已知夫妇中有一方为染色体异常时为夫妇染色体异常组（108个）;除此之外,其他胎儿列为其他因素组（1621个）。采用羊水细胞培养法对各组胎儿进行染色体核型分析,并用荧光原位杂交技术对78个≥26孕周的胎儿行常见非整倍体快速诊断,对153个核型异常胎儿的父母进行淋巴细胞核型分析。结果 (1)各组异常核型分类及其构成：13 795个胎儿中共发现异常核型388个,异常核型发生率为2.813％(388/13 795)。388个异常胎儿中,非整倍体最多,为59.8％ (232/388);常染色体结构异常为24.7％( 96/388);嵌合体为12.4％( 48/388);其他较少见的异常核型包括标记染色体为1.3％ (5/388),性染色体结构异常为1.0％(4/388),三倍体为0.8％(3/388)。除了夫妇染色体异常组,其他各组均以非整倍体占绝大多数,有4例罕见的非整倍体,分别出现在高龄孕妇组、超声异常征象组及血清筛查高危组。超声异常征象组异常核型种类最多,而夫妇染色体异常组其胎儿染色体异常种类最集中（常染色体结构异常）。嵌合体主要分布在血清筛查高危组,占该组异常核型的20.0％ (29/145)。(2)异常核型种类及发生率：异常核型种类中以21三体最为常见,占全部异常核型的35.6％( 138/388),其次为常染色体平衡性结构重排为20.6％ (80/388)、嵌合体为12.4％ (48/388)、18三体为11.3％ (44/388),其他较常见的异常核型包括常染色体非平衡性结构重排和45,X0,各为4.1％(16/388),47,XXY为3.9％(15/388)。(3)父母淋巴细胞核型分析：153个胎儿进行了其父母淋巴细胞的核型分析,并最终确定了胎儿异常核型来源：家族性异常58个,新发生的异常95个。78个胎儿的荧光原位杂交技术诊断结果与G显带核型全部一致,其中2个为21三体。结论不同检查指征孕妇的胎儿异常核型的构成不同;孕中期胎儿异常核型种类繁多,致畸风险与异常核型种类有关。     

Complement factors in fetal and maternal blood and amniotic fluid during the second trimester of normal pregnancy

Summary. Complement factors (C3, C4, C5; Factors B, H and I) were measured in maternal and fetal serum and amniotic fluid obtained from 55 women with singleton pregnancy undergoing diagnostic fetoscopy at 15 to 28 weeks gestation. Maternal serum levels were consistently 10 times higher than fetal levels which in turn were 10 times higher than levels in amniotic fluid. Spearman rank correlation analysis at weeks 20 to 22 (n = 20) revealed a statistically significant correlation between maternal and fetal levels of C3 and Factors B and I, and between maternal and amniotic fluid levels of Factors B and I. A significant increase in fetal levels of C3, C4 and Factor H, and in amniotic fluid levels of C3 and Factor B was seen in relation to advancing gestational age. These differences were not seen in maternal scrum during the short interval of pregnancy studied. These data confirm earlier assumptions of fetal synthesis of complement factors, and provide normal reference ranges of complement factors in fetal blood and amniotic fluid.     

Complement factors in fetal and maternal blood and amniotic fluid during the second trimester of normal pregnancy

Complement factors (C3, C4, C5; Factors B, H and I) were measured in maternal and fetal serum and amniotic fluid obtained from 55 women with singleton pregnancy undergoing diagnostic fetoscopy at 15 to 28 weeks gestation. Maternal serum levels were consistently 10 times higher than fetal levels which in turn were 10 times higher than levels in amniotic fluid. Spearman rank correlation analysis at weeks 20 to 22 (n = 20) revealed a statistically significant correlation between maternal and fetal levels of C3 and Factors B and I, and between maternal and amniotic fluid levels of Factors B and I. A significant increase in fetal levels of C3, C4 and Factor H, and in amniotic fluid levels of C3 and Factor B was seen in relation to advancing gestational age. These differences were not seen in maternal serum during the short interval of pregnancy studied. These data confirm earlier assumptions of fetal synthesis of complement factors, and provide normal reference ranges of complement factors in fetal blood and amniotic fluid.