Radioimmunoassay of placental protein 12: levels in amniotic fluid, cord blood, and serum of healthy adults, pregnant women, and patients with trophoblastic disease

A radioimmunoassay for placental protein 12 (PP12) is described and the levels in amniotic fluid, cord blood, and serum of nonpregnant individuals, pregnant women, and patients with trophoblastic disease are presented. During pregnancy, the highest PP12 levels were found at 22 to 23 weeks (mean +/- SD, 169 +/- 123 ng/ml), and there was a transient decline at 32 to 33 weeks (63 +/- 23 ng/ml). In amniotic fluid, the levels were 100 to 1,000 times higher than in maternal serum. In cord blood at birth, the values were of the same magnitude as in maternal serum. Also healthy nonpregnant women and men had PP12-like immunoreactivity in serum. Nonpregnant women (9 to 47 ng/ml) had higher levels than men (undetectable to 21 ng/ml). Elevated levels up to 84 ng/ml were occasionally observed in trophoblastic disease, both hydatidiform mole and choriocarcinoma, but they bore no correlation with the human chorionic gonadotropin levels. On the basis of these results PP12 is not a suitable marker for trophoblastic disease. PP12 values in normal pregnancy provide the basis for the evaluation of PP12 levels in abnormal pregnancy.     

Labetalol pharmacokinetics in pregnancy-induced hypertension

Pharmacokinetic parameters of oral labetalol were studied in eight women with pregnancy-induced hypertension in the third trimester of pregnancy. Labetalol exhibited rapid absorption; peak serum concentrations of 881 +/- 219 ng/ml occurred at 20 minutes after labetalol ingestion. The terminal elimination half-life (mean, 1.7 +/- 0.27 hours) was found to be shorter than that reported for normotensive volunteers or nonpregnant hypertensive patients (mean, 6 to 8 hours). A mean apparent oral elimination clearance of 21.8 ml/min/kg compared favorably with that seen in other pregnant and nonpregnant populations. Food delayed the time to peak serum concentration to approximately 60 minutes. Labetalol was detected in fetal cord samples and amniotic fluid samples at concentrations approximately 50% and 16% that of simultaneous maternal vein samples, respectively.     

Reduced maternal serum concentrations of angiopoietin-2 in the first trimester precede intrauterine growth restriction associated with placental insufficiency

The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10–13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls ( P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls ( P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR.     

Maternal serum cytokines concentrations during normal pregnancy and labor

OBJECTIVES: The purpose of our study was to determine maternal serum concentrations of IL-8, IL-6, IFN-gamma during normal pregnancy and labor. MATERIALS AND METHODS: Maternal serum IL-8, IL-6 and IFN-gamma levels were measured by means of ELISA technique in 41 healthy pregnant women in 22-42 week gestation and 15 healthy women in labor at term. All newborns and afterbirths had no signs of infection. RESULTS: IL-8 values for pregnant women ranged from 1.98 to 35.2 pg/ml with the median value 10.24 pg/ml, and the 95th percentile 24.5 pg/ml. IL-8 values for women in labor at term ranged from 3.96 to 54.8 pg/ml with the median 10.4 pg/ml. No statistically significant changes in serum IL-8 concentration were observed during pregnancy or in labor. Serum IL-6 concentrations in pregnant women ranged from 0 to 21.7 pg/ml with the median value 0 pg/ml, and the 95th percentile 15.5 pg/ml. Serum IL-6 concentrations in women in labor at term were significantly higher (p < 0.05): ranged from 0 to 39.2 pg/ml with the median 10.1 pg/ml and 95-th percentile 33.5 pg/ml. Maternal serum IFN-gamma concentrations in pregnant women ranged from 0 to 9.8 pg/ml with the median value 3.9 pg/ml, the 95th percentile 9.2 pg/ml and didn't differ during labor at term: range from 0 to 14.5 pg/ml, median 1.9 pg/ml. CONCLUSIONS: Our data revealed that maternal serum IL-8 concentrations didn't changed during the course of pregnancy and in labor. Women in labor had significantly elevated serum IL-6 concentrations compared to those in pregnancy. We didn't observed such changes in serum IFN-gamma levels.     

Serum group II phospholipase A(2) levels during menstrual cycle and pregnancy

The purpose of this study was to evaluate the circulating group II phospholipase A(2) (PLA(2)-II) levels during normal menstrual cycle and to assess alterations in maternal circulating PLA(2)-II concentrations during pregnancy and at puerperium. Circulating serum PLA(2)-II concentrations were compared between 38 nonpregnant women with normal menstrual cycle (15 at menstrual phase, 11 at follicular phase, and 12 at luteal phase), 61 normal pregnant women (13 in the first trimester, 12 in the second trimester, and 36 in the third trimester), and 14 normal postpartum women at 5th puerperal day. Serum PLA(2)-II concentrations were also measured in 11 patients with threatened premature labor. Maternal and fetal serum PLA(2)-II levels before and after delivery were made to determine differences in 11 neonates delivered vaginally and 11 neonates delivered by elective cesarean section. Serum PLA(2)-II level was measured with an immunoradiometric assay. Serum PLA(2)-II concentrations at luteal phase were significantly lower than those at menstrual or follicular phase (p< 0.05). There was no significant difference for PLA(2)-II levels between first trimester and menstrual phase or follicular phase. There were no significant differences among three trimesters during pregnancy. There was no significant difference in serum PLA(2)-II levels between normal pregnant women and patients with threatened premature labor. Labor stress did not affect both maternal and fetal serum PLA(2)-II concentrations. There was also no significant difference for circulating PLA(2)-II levels between maternal and fetal serum. Interestingly, serum PLA(2)-II concentrations in postpartum women were significantly higher than those in normal pregnant women (p<0.05). These results suggest that a regulatory mechanism of PLA(2)-II may exist during the normal menstrual cycle and at puerperium.     

正常妊娠及妊高征患者静脉血及新生儿脐血一氧化氮含量的测…

探讨一氧化氮含量与妊娠及妊高征的关系。方法,采用硝酸根还原酶与Ｇｒｉｅｓｓ反应相结合的方法,对４０例妊高征患者、４０例正常晚期妊娠妇女、２０例非孕妇女静脉血及妊高征组和晚孕组各２８例新生儿脐血中的ＮＯ代谢产物亚硝酸基／硝酸基进行测定。     

Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy

OBJECTIVES: To investigate whether hypertensive disorders of pregnancy alter the maternal and fetal leptin levels. METHODS: Fifty primigravidas between 28 and 34 weeks of gestation were divided into three groups: group A consisted of 17 normal pregnant women with a mean gestational age of 31 weeks, group B consisted of 15 women with gestational hypertension without proteinuria with a mean gestational age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean gestational age of 31 weeks. RESULTS: The pre-eclamptics had significantly higher serum leptin levels than those in normal pregnancies (p<0.001) but no difference was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic women had significantly higher umbilical vein leptin levels (4.68+/-1.66ng/ml) compared to normal pregnancies (1.92+/-0.71ng/ml) and those with gestational hypertension (2.47+/-0.81ng/ml). CONCLUSIONS: Pre-eclampsia is associated with an increase in maternal plasma leptin levels and fetal of leptin production increases in gestational hypertension and even more in pre-eclampsia.     

Pharmacokinetics of orally administered ritodrine

The oral dosing regimen for ritodrine was based in large part on kinetic data obtained in nonpregnant subjects. There are limited kinetic data after oral administration of ritodrine in pregnancy. The purpose of the present study was to compare ritodrine kinetics in pregnant and nonpregnant women, evaluate the effect of feeding on ritodrine absorption in pregnant women, and determine if the plasma concentration of ritodrine is proportional to the dose administered in nonpregnant women. Plasma concentrations after a single 20 mg dose of ritodrine were significantly greater in fasting nonpregnant women than in fasting pregnant women. The area under the concentration time curve was 1372 +/- 385 and 1001 +/- 257 ng/ml/min, respectively. In pregnant women ingesting 20 mg of ritodrine, plasma concentrations were not significantly different in the fed or fasted state; plasma concentrations peaked at 11 ng/ml and were less than 3 ng/ml within 4 hours. In nonpregnant subjects the concentration of ritodrine in plasma was proportional to the dose. After ingestion of 10, 20, or 30 mg of ritodrine, the area under the curve was 751 +/- 253, 1372 +/- 385, and 2148 +/- 571 ng/ml/min, respectively. These data indicate that ritodrine concentrations in pregnant women after a 20 mg oral dose are low. Increases in dosage will probably result in proportional increases in plasma concentration. The maximal dose of ritodrine recommended for prevention of recurrent preterm labor should be increased.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

Serum heat shock protein 70 levels are decreased in normal human pregnancy

Heat shock proteins (Hsps) are primarily known to be intracellular proteins with molecular chaperone and cytoprotective functions. However, Hsp60 and Hsp70 have been found in the serum and plasma of healthy non-pregnant individuals. We aimed to compare serum Hsp70 concentrations in healthy pregnant women with those of healthy non-pregnant women and to determine factors influencing serum Hsp70 levels in normal pregnancy. One hundred and seventy six healthy pregnant women with uncomplicated pregnancies (age, 17-44 years; gestational age, 20-41 weeks) and 81 healthy, age-matched non-pregnant women (age, 22-40 years) were enrolled in this cross-sectional study. Serum Hsp70 concentrations were measured using an enzyme-linked immunosorbent assay, and were significantly lower in healthy pregnant women than in healthy non-pregnant women (median (25-75 percentile): 0.29 (0.20-0.35)ng/ml versus 1.27 (0.86-1.72)ng/ml; p<0.001). In healthy pregnant women, there was a statistically significant negative correlation between maternal age and serum Hsp70 concentration (Spearman R=-0.35; p<0.001) and a significant positive correlation between gestational age and serum Hsp70 level (Spearman R=0.35; p<0.001). The capacity of extracellular Hsp70 to elicit innate and adaptive proinflammatory immune responses might be harmful in pregnancy and lead to immune rejection of the fetal semi-allograft. We hypothesize that decreased circulating Hsp70 levels are due to unknown regulatory mechanisms aimed at maintaining immune tolerance in pregnancy. In conclusion, serum Hsp70 concentrations are decreased in normal human pregnancy; however, further studies are needed to explain the observed differences between pregnant and non-pregnant women.     

孕妇外周血中胎儿DNA水平检测在子痫前期诊断中的应用

目的探讨孕妇外周血中胎儿DNA水平检测在子痫前期诊断中的应用价值。方法选择30例子痫前期孕妇为子痫前期组(其中轻度18例,重度12例),另选择30例正常孕妇作为对照组,两组孕妇分别于孕20周、孕晚期(子痫前期组孕33周+3、对照组孕34周+3)、分娩后1、3、6 h取外周血,采用荧光定量PCR检测外周血中Y染色体上的性别决定基因(SRY基因)胎儿DNA水平(B超确定两组孕妇所妊娠的胎儿均为男性);放射免疫法检测两组孕妇孕晚期内皮素水平。结果(1)子痫前期组孕20周时的胎儿DNA水平为(316±61)copy/m l,其中轻度、重度患者分别为(266±79)、(396±91)copy/m l;对照组孕妇为(165±43)copy/m l,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(2)子痫前期组孕晚期胎儿DNA水平为(970±413)copy/m l,其中轻度、重度患者分别为(758±357)、(1285±573)copy/m l,对照组孕妇为(319±99)copy/m l,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(3)子痫前期组产后1、3、6 h胎儿DNA水平分别为(139±45)、(76±31)、(44±13)copy/m l,其中轻度患者分别为(102±42)、(57±25)、(36±12)copy/m l,重度患者分别为(209±51)、(97±40)、(52±17)copy/m l;对照组分别为(33±13)、(9±5)、0 copy/m l。子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(4)子痫前期组内皮素水平为(80±18)ng/L,其中轻度患者为(74±14)ng/L,重度患者为(89±32)ng/L;对照组为(50±11)ng/L,子痫前期组及轻度、重度患者明显高于对照组,两组比较,差异有统计学意义(P<0.01)。(5)子痫前期组胎儿DNA水平与内皮素水平呈正相关关系(r=0.748,P<0.01)。结论孕妇外周血胎儿DNA水平变化可以作为预测和诊断子痫前期发病与疾病程度的一个指标。     

Accumulation of colony-stimulating factor 1 in amniotic fluid during human pregnancy

Colony-stimulating factor 1 is a hematopoietic growth factor that increases 1000-fold in the uteri of pregnant mice, and its receptor is abundantly expressed in the human placenta. The concentration of colony-stimulating factor 1 in amniotic fluid at 33 to 40 weeks (9.0 +/- 1.1 ng/ml) was twofold higher than that at 16 to 18 weeks gestation (4.1 +/- 0.5 ng/ml), whereas maternal serum colony-stimulating factor 1 levels did not rise significantly. Colony-stimulating factor 1 was detected in endometrial extracts from pregnant women and levels were higher than those in extracts from nonpregnant women.     

Quantitative analysis of DNA levels in maternal plasma in normal and Down syndrome pregnancies

BACKGROUND: We investigated fetal and total DNA levels in maternal plasma in patients bearing fetuses affected with Down syndrome in comparison to controls carrying fetuses with normal karyotype. METHODS: DNA levels in maternal plasma were measured using real-time quantitative PCR using SRY and beta-globin genes as markers. Twenty-one pregnant women with a singleton fetus at a gestational age ranging from 15 to 19 weeks recruited before amniocentesis (carried out for reasons including material serum screening and advanced material age), and 16 pregnant women bearing fetuses affected with Down syndrome between 17 to 22 weeks of gestation were involved in the study. RESULTS: The specificity of the system reaches 100% (no Y signal was detected in 14 women pregnant with female fetuses) and the sensitivity 91.7% (SRY amplification in 22 of 24 examined samples). The median fetal DNA levels in women carrying Down syndrome (n=11) and the controls (n=13) were 23.3 (range 0-58.5) genome-equivalents/ml and 24.5 (range 0-47.5) genome-equivalents/ml of maternal plasma, respectively (P = 0.62). The total median DNA levels in pregnancies with Down syndrome and the controls were 10165 (range 615-65000) genome-equivalents/ml and 7330 (range 1300-36750) genome-equivalents/ml, respectively (P = 0.32). The fetal DNA proportion in maternal plasma was 0%-6 % (mean 0.8%) in women carrying Down syndrome and 0%-2.6 % (mean 0.7 %) in the controls, respectively (P=0.86). CONCLUSIONS: Our study revealed no difference in fetal DNA levels and fetal DNA: maternal DNA ratio between the patients carrying Down syndrome fetuses and the controls.     

Unexplained intrauterine fetal death is accompanied by activation of complement

OBJECTIVE: Activation of the complement system has recently been implicated in the mechanisms of fetal loss in the antiphospholipid syndrome. It is, however, possible that complement activation is also involved in other causes of fetal death in the second and third trimesters of pregnancy. We therefore conducted a study to determine whether fetal death is associated with changes in the maternal plasma concentrations of complement split products or anaphylatoxins (C3a, C4a and C5a). STUDY DESIGN: A cross-sectional study was designed to include normal pregnant women (n=60) and patients with fetal death (n=60). Patients with fetal death were classified according to the cause of fetal demise into: a) unexplained (n=44); b) associated with preeclampsia (n=8); and c) associated with chromosomal abnormalities or major congenital fetal anomalies (n=8). The plasma concentrations of C3a, C4a and C5a were measured using sensitive and specific ELISAs. Non-parametric statistics were used for analysis. A P value of <0.05 was considered significant. RESULTS: 1) The median plasma concentration of C5a was higher in patients with fetal death than in normal pregnant women [median 16 ng/mL (range 4.5-402.5) vs. median 11.6 ng/mL (range 1.2-87.1), respectively; P<0.001]; 2) patients with an unexplained fetal death and those associated with preeclampsia had a higher median plasma C5a concentration than normal pregnant women (P=0.002 and P<0.001, respectively); 3) no differences were observed in the maternal plasma concentrations of C3a and C4a among the study groups. CONCLUSIONS: Unexplained fetal death is associated with evidence of complement activation.     

Maternal and fetal serum nitric oxide (NO) concentrations in normal pregnancy, pre-eclampsia and eclampsia.

OBJECTIVES: To measure the maternal and fetal serum concentrations of total nitrites and nitrates (as an index of nitric oxide production) in normal pregnancy, pre-eclampsia and eclampsia. DESIGN: Three groups of women were studied cross-sectionally: late pregnant women with pre-eclampsia and eclampsia (n=31); normal late pregnant women (n=32); and age-matched healthy non-pregnant women (n=21). Venous blood samples were collected from all women and both maternal and umbilical venous samples were collected from pregnant women. METHODS: Blood samples were assayed for nitric oxide (NO) production by Greiss reaction which measures the combined oxidation products of NO (total nitrites and nitrates). RESULTS: There was a significant increase in serum total nitrites and nitrates concentrations in normal pregnant women than in the serum of age-matched normal non-pregnant women (P<0.0001). Significantly higher total nitrites and nitrates levels were found in the maternal sera of the pre-eclamptic and eclamptic women compared with those of normal pregnant women (P<0.0001). Also, fetal blood levels of total nitrites and nitrates were significantly increased in pre-eclampsia and eclampsia compared with those of normal pregnancy (P<0.0001). CONCLUSIONS: (1) Serum nitric oxide (NO) production is increased in normal pregnancy than in the normal non-pregnancy. (2) Maternal and fetal serum NO levels are increased significantly in pre-eclampsia and eclampsia, which possibly represents a compensatory/protective mechanism to maintain blood flow and limit platelets aggregation in the fetal-maternal circulations. (3) The increase in NO production is directly related to the severity of pre-eclampsia; this would be of diagnostic significance for the prediction of the severity of this syndrome.     

Estimation of passive smoking during pregnancy by cotinine measurement and its effect on fetal growth

Maternal cigarette smoking has been associated with some complications of pregnancy, including low birth weight and increased morbidity. Recently, it has been reported that maternal passive smoking also affects the fetal environment and causes fetal growth disturbance. In this study, we aimed to investigate the effects of maternal passive smoking on pregnant women and their fetuses by measuring cotinine concentrations in maternal urine and umbilical cord blood. The results were as follows: 1) Among 259 pregnant women, 17 cases (6.6%) were active smokers. The women who were not aware of passive smoking at all, were only 39 cases (15.1%). More than 80% of the pregnant women smoked either passively or actively each day. 2) Cotinine concentrations in both maternal urine and umbilical cord blood increased with the increase in passive smoking. Those in maternal serum, however, did not correlate with the increase in passive smoking. 3) The relative birth weight (R.B.W.) of the newborn infants delivered by the mothers whose cotinine concentration was more than 9.0ng/ml (This value represented the mean +1.5SD of the cotinine concentration in the urine from the mother who did not passively or actively smoke) was significantly lower than that of the mothers whose cotinine concentration was less than 9.0ng/ml. It is concluded that the measurement of the cotinine concentration in maternal urine or umbilical cord blood is very useful in estimating the effects of passive smoking on pregnant women. And passive smoking as well as active smoking also has a harmful effect on the fetal growth mechanism.     

Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia.

OBJECTIVES: Placental growth hormone (PGH) is a pregnancy-specific protein produced by syncytiotrophoblast and extravillous cytotrophoblast. No other cells have been reported to synthesize PGH Maternal. PGH Serum concentration increases with advancing gestational age, while quickly decreasing after delivery of the placenta. The biological properties of PGH include somatogenic, lactogenic, and lipolytic functions. The purpose of this study was to determine whether the maternal serum concentrations of PGH change in women with preeclampsia (PE), women with PE who deliver a small for gestational age neonate (PE + SGA), and those with SGA alone. STUDY DESIGN: This cross-sectional study included maternal serum from normal pregnant women (n = 61), patients with severe PE (n = 48), PE + SGA (n = 30), and SGA alone (n = 41). Fetal cord blood from uncomplicated pregnancies (n = 16) and PE (n = 16) was also analyzed. PGH concentrations were measured by ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) Women with severe PE had a median serum concentration of PGH higher than normal pregnant women (PE: median 23,076 pg/mL (3473-94 256) vs. normal pregnancy: median 12 157 pg/mL (2617-34 016); p < 0.05), pregnant women who delivered an SGA neonate (SGA: median 10 206 pg/mL (1816-34 705); p < 0.05), as well as pregnant patients with PE and SGA (PE + SGA: median 11 027 pg/mL (1232-61 702); p < 0.05). (2) No significant differences were observed in the median maternal serum concentration of PGH among pregnant women with PE and SGA, SGA alone, and normal pregnancy (p > 0.05). (3) Compared to those of the control group, the median umbilical serum concentration of PGH was significantly higher in newborns of preeclamptic women (PE: median 356.1 pg/mL (72.6-20 946), normal pregnancy: median 128.5 pg/mL (21.6-255.9); p < 0.01). (4) PGH was detected in all samples of cord blood. CONCLUSIONS: (1) PE is associated with higher median concentrations of PGH in both the maternal and fetal circulation compared to normal pregnancy. (2) Patients with PE + SGA had lower maternal serum concentrations of PGH than preeclamptic patients without SGA. (3) Contrary to previous findings, PGH was detectable in the fetal circulation. The observations reported herein are novel and suggest that PGH may play a role in the mechanisms of disease in preeclampsia and fetal growth restriction.     

Increased serum retinol-binding protein 4 concentrations in women with gestational diabetes mellitus

The authors hypothesized that serum retinol-binding protein 4 (RBP4) concentrations will be higher in gestational diabetes mellitus (GDM) subjects. This study tested both women with GDM and healthy pregnant women and correlated their serum RBP4 concentrations with body mass index (BMI) and a variety of other parameters. Also, since there is no information on the relationship between RBP4 concentrations in maternal and fetal serum, this study measured these at delivery and examined whether there were correlations between the cord serum RBP4 levels and maternal serum RBP4 concentrations, neonatal birth weights, and gestational age at delivery. A total of 40 women were evaluated: 20 women with GDM and 20 healthy pregnant women to serve as control subjects. Serum RBP4 concentrations were analyzed with the use of an enzyme-linked immunosorbent assay kit. Serum RBP4 concentrations at glucose challenge test (GCT) were significantly higher in the GDM group (42.4 +/- 13.8 ng/mL) than in the healthy control group (32.0 +/- 8.7 ng/mL; P = .007). BMI at GCT (P = .003) and GDM/no GDM (P = .014) were significantly correlated to serum RBP4 concentrations at GCT by multiple linear regression analysis. In GDM subjects, serum RBP4 concentrations immediately after delivery were significantly lower than those at GCT (30.1 +/- 11.0 ng/mL, 42.4 +/- 13.8 ng/mL; P < .001), but there was no such difference in normal subjects (30.9 +/- 10.0 ng/mL, 32.0 +/- 8.7 ng/mL; P = .581). Cord serum RBP4 concentrations were significantly lower than maternal serum RBP4 concentrations at delivery (10.9 +/- 3.8 ng/mL, 30.5 +/- 10.4 ng/mL; P < .001). Only fetal birth weight (P = .049) was independently related to cord serum RBP4 concentrations at delivery by multiple linear regression analysis. This study found increased serum RBP4 concentrations at GCT in GDM subjects, and GDM was significantly correlated to serum RBP4 levels after adjustment for the effect of BMI. Lower RBP4 concentrations were found at delivery in GDM subjects. Maternal serum RBP4 concentrations were significantly higher than cord serum RBP4 concentrations, and fetal birth weights were independently correlated to cord serum RBP4 concentrations. These findings may indicate that RBP4 plays a role in the pathogenesis of GDM. However, further experiments are required to clarify this role and find a possible regimen for GDM treatment.     

妊娠早期孕妇血清瘦素、β-hCG及融合素α(ADAM12)水平与自然流产发生的相关性研究

目的:探讨妊娠早期妇女血清瘦素、人绒毛膜促性腺激素β(β-hCG)及融合素-α(ADAM12)的浓度变化及这些指标对自然流产发生的预测价值。方法:分别测定172例妊娠妇女(其中自然流产者20例)及非妊娠健康妇女48例,妊娠组在孕10～12周时分别测血清瘦素、β-hCG、ADAM12的浓度。瘦素、β-hCG采用ELISA法测定,ADAM12采用时间分辨荧光免疫分析方法测定,预测界限值根据ROC曲线确定。结果:①在妊娠早期自然流产患者血清β-hCG、瘦素、ADAM12水平低于正常妊娠者,差异显著(P<0.001);自然流产组、正常妊娠组β-hCG、瘦素水平均高于非妊娠组,差异显著(P<0.05)。②妊娠早期以血清瘦素≤11 ng/ml、血清β-hCG≤22 IU/ml及血清ADAM12≤335 ng/ml为预测界值,其预测自然流产发生的曲线下面积、灵敏度、特异度、阳性预测值(PPV)及阴性预测值(NPV)分别为:79.60%、90.00%、71.71%、29.51%和98.20%;91.00%、85.00%、87.50%、47.22%和97.79%;78.40%、80.00%、78.75%、48.48%和94.03%。③根据ROC曲线图确定临界值:以血瘦素≤11 ng/ml、血β-hCG≤22 IU/ml为预测界值,两者联合灵敏度75%,特异度96.05%,阳性预测值71.43%,阴性预测值96.69%,两者联合预测阳性率显著高于单项血清β-hCG及瘦素预测率(P<0.05)。④根据ROC曲线图确定临界值:以血β-hCG≤22 IU/ml、血ADAM12≤335 ng/ml为预测界值,两者联合灵敏度75%、特异度95%,阳性预测值78.95%,阴性预测值93.83%,两者联合预测阳性率显著高于单项血清β-hCG及ADAM12预测率(P<0.05)。结论:妊娠早期,检测孕妇血瘦素、β-hCG及ADAM12,可作为自然流产发生的有效预测指标;联合多项指标可进一步提高对自然流产发生的阳性预测率及准确率。