Placental protein 21. Localization in human placenta and concentrations in the body fluids of men and nonpregnant and pregnant women

The immunohistochemical localization of placental protein 21 (PP21) was marked in the syncytial brush border and basal membrane during the 1st and 2nd trimesters of pregnancy and also in the chorionic epithelial brush border and basement membrane at term. A weaker stain was found in the cell membranes of amniotic epithelial and chorionic trophoblast cells. Neither heparin nor changes in temperature significantly influenced PP21 concentration. Relatively high serum PP21 concentrations were measured during the follicular and luteal phases in healthy nonpregnant women and in healthy men whose seminal plasma also showed a high PP21 concentration. Serum PP21 levels in normal pregnancy rose from a median of 29.1 ng/ml at 6-7 weeks of gestation to 82.0 ng/ml at 36-37 weeks of gestation. Although maternal urine showed low PP21 levels during pregnancy, amniotic fluid PP21 levels were higher at 7-21 weeks of gestation than at term. Cord blood sera showed almost the same PP21 concentration as maternal sera, but retroplacental blood showed much higher levels. Maternal serum PP21 levels in hydatidiform mole patients did not differ from the normal pregnancy range, although their molar vesicular fluids contained higher PP21 concentrations. These results suggest an extraplacental source for PP21.     

Serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies

A prospective study was initiated to closely examine maternal serum concentrations of CA-125 during the early first trimester of normal and abnormal pregnancies. Sequential serum specimens were obtained from 43 women with a normal intrauterine pregnancy, 20 with a surgically confirmed ectopic gestation and 10 whose pregnancies ended in spontaneous abortion. In normal pregnancies the CA-125 levels increased significantly from the first week after the missed menses (39.9 +/- 8.2 U/mL [mean +/- SEM]) to the second week (48.3 +/- 6.9 U/mL) (P less than .05) and from the second to the third week (62.5 +/- 9.8) (P less than .05). After the third week after the missed menses the mean CA-125 serum concentrations plateaued, but levels observed during the fourth (59.6 +/- 8.8 U/mL) and fifth (48.8 +/- 7.2 U/mL) weeks were still significantly greater than at week 1. In addition, the mean CA-125 concentrations were significantly higher in normal pregnancies than in ectopic gestations during the second, third and fourth weeks after the missed menses. Although there was a tendency for the CA-125 levels to be lower in women who had a spontaneous abortion when compared to normals, these differences were not statistically significant. Serum levels of CA-125 may prove useful in monitoring early pregnancy.     

Placental protein 10 (PP10) in normal pregnancy and cholestasis of pregnancy

The circulating concentrations of placental protein 10 (PP10) were measured by radioimmunoassay in 288 women with normal pregnancy and ten women (55 samples) with cholestasis of pregnancy. Serum PP10 levels were not affected by changes in incubation and storage temperature, and no diurnal variation was observed. The highest PP10 levels (36-85 micrograms/l) in normal pregnancy were found at 34 weeks. The postpartum decline of serum PP10 concentration corresponded to an average half-life of 18 h. In cholestasis of pregnancy at 32-39 weeks, the serum PP10 levels were found to be lower than normal. Negative correlation was observed between aminotransferase and PP10 levels in serum and between the bile acid levels and the PP10 concentration. These results suggest that the severity of maternal liver disorder is reflected in the circulating PP10 concentration.     

Placental protein 10 (PP10) in normal pregnancy and cholestasis of pregnancy

Summary. The circulating concentrations of placental protein 10 (PP10) were measured by radioimmunoassay in 288 women with normal pregnancy and ten women (55 samples) with cholestasis of pregnancy. Serum PP10 levels were not affected by changes in incubation and storage temperature, and no diurnal variation was observed. The highest PP10 levels (36–85 μg/1) in normal pregnancy were found at 34 weeks. The postpartum decline of serum PP10 concentration corresponded to an average half-life of 18h. In cholestasis of pregnancy at 32–39 weeks, the serum PP10 levels were found to be lower than normal. Negative correlation was observed between aminotransferase and PP10 levels in serum and between the bile acid levels and the PP10 concentration. These results suggest that the severity of maternal liver disorder is reflected in the circulating PP10 concentration.     

Human chorionic gonadotropin levels in pregnancies with aneuploid fetuses

Maternal serum human chorionic gonadotropin (hCG) and the free alpha-hCG subunit were evaluated in 249 women from 9 to 11 weeks gestation who subsequently underwent chorionic villus sampling for determination of fetal karyotype and in 20 women of 18 or more weeks gestation who were ascertained to have an aneuploid fetus by genetic amniocentesis. Seven of the first-trimester pregnancies were determined to be aneuploid and six had hCG levels in the normal range (one triploid pregnancy had elevated hCG levels) whereas 12 of the 20 second-trimester cases had abnormal hCG levels and an additional three had elevated levels of alpha-hCG. This study confirms the previous report of abnormal maternal serum hCG levels in women with an aneuploid fetus at greater than or equal to 18 weeks gestation and demonstrates that hCG evaluation is not useful at 9-11 weeks gestation for selecting pregnancies at risk for fetal aneuploidy.     

Longitudinal analysis of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in antiphospholipid syndrome and in healthy pregnancy

OBJECTIVE: The purpose of this study was to determine the concentrations of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in pregnancies that are complicated with primary antiphospholipid syndrome. STUDY DESIGN: Longitudinal blood samples were collected from 8 weeks of gestation in 28 women with treated primary antiphospholipid syndrome and 19 control women. Serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 were measured by immunoradiometric assay. RESULTS: Three antiphospholipid syndrome pregnancies miscarried, four pregnancies had intrauterine growth restriction and preeclampsia, six pregnancies had a thrombotic event, and one pregnancy had abruptio placentae. Mean (+/-SD) birth weight in antiphospholipid syndrome group was 2867 +/- 914 g (control, 3492 +/- 527 g; P =.02), and the mean gestation at delivery was 36.5 +/- 5.2 weeks (control, 40.3 +/- 0.7 weeks; P =.002). Insulin-like growth factor binding protein-1 and insulin-like growth factor-I concentrations increased with gestational age in both groups (2.8% and 2.4% per week), but insulin-like growth factor binding protein-1 was 61% higher in the antiphospholipid syndrome group (95% CI, 16%-122%; P =.004). Insulin-like growth factor-I was not significantly different (8% higher in antiphospholipid syndrome; 95% CI, -10% to 30%; P =.41). CONCLUSION: Serum concentrations of insulin-like growth factor binding protein-1 are abnormal in the antiphospholipid syndrome group and may reflect abnormalities in trophoblast invasion.     

Prospective analysis of placenta growth factor (PlGF) concentrations in the plasma of women with normal pregnancy and pregnancies complicated by preeclampsia.

OBJECTIVE: The aim of this study was to analyze if levels of plasma PlGF in the second half of pregnancy have predictive value for the identification of women destined to develop preeclampsia or another complication of pregnancy. Material and METHODS: A bank of 1.543 randomly collected plasma samples (22-29 weeks of gestation) was established and PlGF concentrations were quantitated in a prospective longitudinal study in all pregnant women who developed a complication of pregnancy in late gestation (177 of 1.543) and the same number of gestational age matched pregnancies with normal outcome. RESULTS: Plasma PlGF levels in pregnant women rise steadily throughout pregnancy from the level of nonpregnant women (< 50 pg/mL) to levels exceeding 500 pg/mL after 30 weeks of gestation. Just 7.3% of pregnant women with normal outcome of pregnancy had PlGF levels of less than 200 pg/mL beyond 22 weeks of gestation (3.7% beyond 25 weeks of gestation). The rise in plasma PlGF in the second half of pregnancy was significantly attenuated in pregnancies that were complicated by preeclampsia in late gestation. Of all women who developed preeclampsia, 27.3% (12 of 44) had plasma PlGF levels below 200 pg/mL. The attenuation of the rise in plasma PlGF was not evident in other complications of pregnancy (transient hypertension, fetal retardation, pregnancy diabetes, premature contractions, proteinuria without hypertension, infections during pregnancy). CONCLUSION: The rise in plasma PlGF levels observed in normal pregnancies is significantly attenuated in pregnancies complicated by preeclampsia. Yet, due to the low sensitivity and specificity, plasma PlGF levels in the second half of pregnancy have no predictive value for the identification of individual women destined to develop preeclampsia.     

Human chorionic gonadotropin and relaxin concentrations in early ectopic and normal pregnancies.

The present study was performed to investigate whether determination of serum relaxin concentrations would allow assessment of the gestation further than that provided by determination of hCG. Serum relaxin concentrations were quantified in women with resorbing ectopic gestations (as documented by declining titers of beta-hCG). The control group consisted of individuals with intrauterine pregnancies. As an additional control, we studied pregnancies conceived through ovulation induction, which usually have an increased volume of relaxin-secreting luteal tissue. On days 39-70 of gestation, the mean serum relaxin concentrations were significantly lower in ten resorbing ectopic gestations (P less than .001, permutation test) than in the normal control group of 13 intrauterine pregnancies. The median serum relaxin concentrations in patients who had ovulation induction with Pergonal were substantially higher than the median for all normal controls; values in clomiphene citrate-treated patients were within the normal range. These data suggest that relaxin secretion correlates with luteal function in both normal and abnormal gestations and reflects the status of the pregnancy. Thus, relaxin may serve as a useful clinical marker.     

Single radial immunodiffusion of human placental lactogen and its clinical uses

This paper reported the serum hPL levels in 318 normal and abnormal pregnancies as determined by hPL-single radial immunodiffusion (SRID). The results indicated that serum hPL levels in the normal pregnancies increased with the advance of gestational weeks, while sustained low levels of hPL were observed in most abnormal pregnancies. Serum hPL levels varied with the severity of the pregnancy induced hypertension, fetal weight and the duration of post-term pregnancy. When the serum hPL level of the gestational woman was less than or equal to 4 mg/L, the incidence of low Apgar score was 42% (P less than 0.01). It is thought that measuring serum hPL levels is a useful index for detecting placental insufficiency and predicting fetal prognosis.     

The relationship of maternal serum levels of Il-6 and TNF-alpha with fertility and parity of women with pregnancies complicated by PROM

OBJECTIVE: The aim of the study was to assess the relationship of maternal serum IL-6 and TNF-alfa levels with fertility and parity of women with pregnancies complicated by premature rupture of membranes (PROM). MATERIALS AND METHODS: The maternal serum of IL-6 and TNF-alfa levels were evaluated in patients with PROM between 24-34 weeks of pregnancy (the study group, n = 45). The control group consisted of healthy pregnancy (n = 41) at 24-34 weeks of gestation. Serum cytokines concentrations were measured by commercial available enzyme-linked immunosorbent assays. C-reactive protein level and WBC were estimated in both groups. RESULTS: The positive correlation between maternal serum TNF-alfa and fertility (R = 0.322, p = 0.042), and parity (R = 0.339, p = 0.032) in patients in the study group was found. No relationship of evaluated cytokines, CRP, WBC with fertility and parity was found in healthy pregnancy women. Compared to primigravidas, multiparas with PROM had significantly higher serum levels of TNF-alfa (1571.41 pg/ml vs 854.54 pg/ml, p = 0.014); serum IL-6 levels was significantly higher in patients with fourth delivery or more compared to patients with third delivery and less (32.32 pg/ml vs 5.52, p = 0.039). CRP concentration and WBC were comparable in those groups. CONCLUSION: 1. Women with at least one pregnancy in the past are at higher risk of premature rupture of membranes in following pregnancies. 2. Every suspicion of intrauterine infection or presence of potential risk factors such as bacterial vaginosis, cervicitis, kolpitis or urinary tract infection should be carefully evaluated in this group of patients.     

Circulating levels of placental protein 10 (PP10) in diabetic pregnancy

Circulating levels of placental protein 10 (PP10) were measured in 217 heparinized plasma samples from 35 insulin-dependent diabetic patients and 90 samples from apparently healthy pregnant women between 15 and 40 weeks. In diabetic pregnancy between 15 and 40 weeks, the levels were significantly below normal (p less than 0.001). Decreased PP10 levels were seen especially in those cases where diabetic pregnancy was complicated by intra-uterine growth retardation, intra-uterine death, or severe congenital malformation. In 9 healthy pregnant women the PP10 levels were measured both in heparinized plasma and in serum samples. The plasma values were 76% of those in serum, suggesting interaction between PP10 and heparin.     

Radioimmunoassay of serum SP 1 and HPL in normal and abnormal pregnancies.

Serum concentrations of the pregnancy-specific beta 1-glycoprotein (SP 1) and human placental lactogen (HPL) were measured by radioimmunoassay in 372 blood samples obtained from 40 women in the second half of a normal singleton pregnancy. The mean level of SP 1 steadily increased from 40 micrograms/ml in the 22nd week of pregnancy to 168 micrograms/ml in the 36th week of gestation and thereafter reached a plateau. The half-life of SP 1 during the first week after delivery was about 39 h. The clinical value of SP 1 in comparison to HPL estimations was assessed in a prospective study of a few high risk pregnancies. There were no significant differences between serum SP 1 and HPL levels in pregnancies complicated by preeclampsia with or without intrauterine growth retardation and in twin pregnancies. Serum HPL and SP 1 levels were equally effective in predicting placental insufficiency with fetal growth retardation.     

Parathyroid hormone and calcitriol changes in normal and insulin-dependent diabetic pregnancies

In pregnancy, an increase in serum calcitriol and parathyroid hormone concentrations has been reported in several studies, though the increase in parathyroid hormone remains controversial. In magnesium deficiency states, parathyroid hormone and calcitriol secretion may be decreased. Because magnesium deficiency may occur in insulin-dependent diabetic patients, mainly because of urinary magnesium losses, we hypothesized that serum parathyroid hormone and calcitriol do not increase in the diabetic pregnancy. We studied, in a prospective longitudinal manner, 35 nondiabetic and 199 insulin-dependent diabetic pregnancies. In diabetic women, the goals of glycemic control were fasting blood glucose below 100 mg/dL and postprandial blood glucose less than 140 mg/dL. Serum magnesium, calcium, parathyroid hormone (whole molecule; ie, 1-84 fragment), and calcitriol were measured three times: 1) 8-12 weeks, 2) 22-28 weeks, and 3) 32-38 weeks' gestation. In normal women, serum parathyroid hormone did not change significantly over pregnancy, and a wide scatter of values was observed. Serum calcitriol increased significantly with advancing gestation. In diabetic women, serum parathyroid hormone had a narrow scatter, but values were within the low-normal range. During the third trimester there was no increase, and even a decrease, in serum calcitriol concentrations. Diabetics had, throughout pregnancy, significantly reduced serum magnesium concentrations when compared with controls. Their serum calcium and ionized calcium concentrations were similar to those of controls, except in the third trimester, when diabetic women had significantly lower serum calcium and ionized calcium concentrations than controls. We speculate that mineral metabolism abnormalities in diabetic pregnancies might be due to relative magnesium and/or insulin deficiency.     

Placental protein 10 (PP10) in singleton and twin pregnancy complicated by pre-eclampsia

Summary Circulating levels of placental protein 10 (PP10) were measured by radioimmunoassay in 140 women with normal singleton pregnancy (140 samples), in 6 women with normal twin pregnancy (15 samples) and in 35 pregnant women with pre-eclampsia (51 samples from singleton pregnancies and 7 samples from twin pregnancies) between 24 and 40 weeks. In singleton pregnancies with pre-eclampsia, the levels were lower than normal (P<0.01). In twin pregnancy the circulating PP10 levels were not significantly affected. These results suggest that changes in placental function are reflected in the circulating PP10 levels.     

Maternal zinc status: a determination of central nervous system malformation

Summary. Maternal serum zinc concentrations were estimated during 244 normal pregnancies and 15 abnormal pregnancies. The serum zinc concentrations were lower in the anencephalic pregnancies than in the normal control subjects. The serum zinc levels in women whose pregnancies terminated in a spontaneous abortion were normal. There was no variation of serum zinc level with gestational age between 15 to 18 weeks in normal pregnancies.     

Maternal zinc status: a determination of central nervous system malformation

Maternal serum zinc concentrations were estimated during 244 normal pregnancies and 15 abnormal pregnancies. The serum zinc concentrations were lower in the anencephalic pregnancies than in the normal control subjects. The serum zinc levels in women whose pregnancies terminated in a spontaneous abortion were normal. There was no variation of serum zinc level with gestational age between 15 to 18 weeks in normal pregnancies.     

Studies on serum CA125 levels in pregnant women

To confirm the change in serum CA 125 levels in cases of pregnancy, we measured serum CA 125 levels in 234 normal pregnant women, 40 postpartum women and 14 abnormal pregnant women (12 of IUFD and 2 of H. mole), using an RIA kit. The mean CA 125 level (+/- S.D.) and positive ratio (greater than 34U/ml) for pregnant women at 4-11 weeks of gestation were 65.0 +/- 77.3 U/ml and 64.6%, respectively, being the highest values in all the groups. On the contrary, those for pregnant women at 12-23 weeks of gestation were 22.3 +/- 10.6 U/ml and 12.7%, respectively, the lowest in all gestational groups. Changes in serum CA 125 levels in normal pregnant women showed a trend toward decrease, as gestation advanced. But the CA 125 levels for women at postpartum showed a slight trend toward increase. The mean CA 125 level (+/- S.D.) for 12 patients with IUFD was 392.5 +/- 275.8 U/ml and that for 2 patients with H. mole was 65.0 +/- 15.0 U/ml. Serum CA 125 levels for patients with IUFD were higher than that in cases of normal pregnancy. When utilizing CA 125 as a marker for ovarian cancer, the influence of pregnancy must be considered. And it indicates that CA 125 can be used as an aid to the diagnosis of IUFD in serous cases.     

Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies

OBJECTIVE: Complicated pregnancies demonstrate abnormal decidual and placental villous vasculature. We examined maternal concentrations of vascular endothelial growth factor and placental growth factor in normal pregnancies and in pregnancies that were complicated by isolated idiopathic small-for-gestational-age (SGA) newborn infants, preeclampsia alone, or preeclampsia with SGA newborn infants at the time of clinical disease and before the onset of clinical signs. STUDY DESIGN: Serum vascular endothelial growth factor and placental growth factor were measured by enzyme-linked immunosorbent assay in cross-sectional and longitudinal cohorts of pregnant nulliparous women. The results were compared by Wilcoxon tests or a mixed-models method, respectively. RESULTS: In the cross-sectional study, serum placental growth factor was reduced in abnormal pregnancy relative to control subjects (SGA newborn infants, 18 [P =.04]; preeclampsia, 20; or preeclampsia with small- for-gestational-age newborn infants, 11 [P =.0001]) as early as 15 to 19 weeks of gestation in preeclampsia with SGA newborn infants. Vascular endothelial growth factor was <30 pg/mL in all serum specimens from pregnant women. CONCLUSION: We postulate that decreased placental growth factor production results in abnormalities of placental angiogenesis through direct and indirect effects on other vasculotropic growth factors.     

正常妊娠和妊娠高血压综合征妇女血清瘦素水平的动态检测

目的　动态检测正常妊娠、妊娠高血压综合征 (妊高征 )妇女血清瘦素水平的变化特点。方法　采用放射免疫法测定 40例正常非妊娠妇女 (对照组 )以及 5 0例正常妊娠和 14例妊高征妇女(观察组 )孕 16～ 2 0、2 4～ 2 8、3 2～ 3 6周及分娩前的血清瘦素水平及其新生儿的脐血瘦素水平 ,同时测量身高、体重、血压及胎盘重量。结果　 ( 1)随着孕周的增加 ,观察组妇女血清瘦素水平呈上升趋势 ,其中妊高征妇女血清瘦素水平为 ( 14 1± 2 2 )～ ( 2 5 4± 2 7) μg/L ,较正常妊娠妇女的 ( 13 4± 3 0 )～( 2 1 4± 3 7) μg/L明显上升 (P <0 0 1) ,并持续至妊娠结束 ,而正常妊娠妇女血清瘦素水平在孕 2 8～3 6周时上升明显 ,孕 2 8周前及孕 3 6周后上升缓慢。 ( 2 )体重、体重指数与血清瘦素水平的相关性分析结果显示 ,正常妊娠、对照组妇女均呈显著性正相关 (r =0 478～ 0 63 9,P <0 0 5或P <0 0 1) ,而妊高征妇女无显著相关性 (r=0 0 3 5～ 0 3 79,P >0 0 5 )。( 3 )收缩压、舒张压、平均动脉压与血清瘦素水平的相关性分析结果显示 ,正常妊娠、孕 2 0周前的妊高征及对照组妇女无显著相关性 (r=0 113～0 498,P >0 0 5 ) ,而妊高征妇女孕 2 0周后呈显著正相关 (r=0 63 9～ 0 85 2 ,P <0 0 5 )     

The effects of oral iron supplementation on zinc and magnesium levels during pregnancy

Summary. Serial changes in serum zinc and magnesium concentrations have been studied before conception, throughout pregnancy and at 12 weeks postpartum in 15 normal healthy women not receiving iron supplementation, 10 women receiving iron supplementation but other-wise having healthy pregnancies and five insulin-dependent diabetics who also received oral iron . Relative to pre-pregnancy values zinc concentrations progressively decreased throughout pregnancy reaching a nadir at 36 weeks gestation followed by an increase; pre-pregnancy values were achieved by 12 weeks postpartum. Magnesium concentrations also decreased throughout pregnancy reaching a nadir at 32 weeks gestation increasing thereafter again with pre-pregnancy values achieved by 12 weeks postpartum. Iron supplementation in non-diabetic and diabetic women had no significant effect upon the changes in serum concentration of either zinc or magnesium. These results suggest that the decrease in the concentrations of both elements is a normal physiological adjustment to pregnancy and that iron supplementation does not influence these changes