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.     

First-trimester maternal serum PAPP-A,SP1 and M-CSF levels in normal and trisomic twin pregnancies

OBJECTIVE: To study PAPP-A and SP1 for biochemical trisomy screening in twin pregnancies and to investigate the role of maternal and placental compartments in marker production by comparing the levels of the decidual cytokine M-CSF with the PAPP-A and SP1 from the placenta. METHODS: Thirteen twin pregnancies with at least one chromosomally abnormal fetus were compared with 68 normal twin pregnancies. Sera were obtained between 11 + 3 and 13 + 6 weeks of gestation, and PAPP-A, SP1 and M-CSF levels were determined by immunoassay. These concentrations were also compared with gestation-matched groups of 18 singleton normal pregnancies and 18 singleton Down syndrome pregnancies. RESULTS: PAPP-A and SP1, but not M-CSF, levels were higher in normal twin pregnancy than in normal singleton pregnancy. SP1 levels, but not PAPP-A, correlated to M-CSF. PAPP-A, but not SP1, levels were reduced in abnormal twin pregnancies, with an increasing effect according to the number of affected fetuses, and were more pronounced in pregnancies with trisomy 18 or 13 than in trisomy 21 fetuses. M-CSF was inconsistent, with a trend towards increased levels in trisomy 21. CONCLUSION: PAPP-A remains the best biochemical screening marker for fetal trisomies 21, 18 or 13, in singleton as well as in twin pregnancy. In contrast to SP1, its site of production is not likely to be restricted to the placenta. The role of the (maternally produced) M-CSF remains to be further investigated.     

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.     

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.     

Circulating levels of placental protein 5 in normal and abnormal pregnancies

Serum concentrations of PP5 were measured by radioimmunoassay in 219 women with normal pregnancies and 163 women whose pregnancies were complicated. PP5 in serum disappeared rapidly after delivery, with a half-life of 5-10 min in the first 10 min. Serum PP5 levels were higher in uterine than in antecubital venous blood. In normal pregnancies, PP5 was detectable at 7-8 weeks of gestation; its mean concentration rose gradually to a maximum of 17.8 +/- 10.2 ng/ml at 34-35 weeks of gestation. Elevated serum PP5 concentrations were noted in patients whose pregnancies were complicated by toxemia of pregnancy with appropriate-for-date baby or by twin pregnancy. Low serum PP5 concentrations tended to be found in patients whose pregnancies were complicated by abortion, intrauterine fetal death, and hydatidiform mole. Marked abnormal PP5 levels were not found in patients with maternal diabetes and placenta previa. These findings suggest that the assay of serum PP5 concentrations can be a useful parameter in determining the prognosis of abnormal pregnancies.     

Neonatal and maternal serum levels of soluble ICAM-1 in preeclamptic and normal pregnancies

The aim of this study is to determine whether circulating levels of sICAM-1 were changed in infants of preeclamptic mothers, and factors influencing these levels. Peripheral venous blood samples were obtained from preeclamptic and nonpreeclamptic pregnant women (control) and their babies in the first 2 hours post partum. The enzyme-linked immunoadsorbent assay (ELISA) technique was used to determine concentrations of sICAM-1. Compared with the control group, maternal and neonatal serum sICAM-1 levels were higher in the preeclamptic group. Neonatal levels were correlated with the maternal levels only, and there were no difference between premature and term babies and their mothers. In the control group, on the other hand, premature babies and their mothers had higher sICAM-1 levels than term babies and their mothers, with values close to those of premature group in the preeclamptic group. Neonatal sICAM-1 levels were correlated with gestational age, birth weight, and also with maternal levels. Linear regression analysis of these parameters, however, showed that only the gestational age was significant. The study suggests that perinatal sICAM-1 levels possibly are not independent from the maternal levels. High sICAM-1 levels in infants of preeclamptic mothers and premature babies might reflect the high maternal levels.     

Immunoglobulin levels in maternal and neonatal sera from normal and abnormal pregnancies

IgG, IgM and albumin levels in sera from neonates with open neural tube defects (NTD), other congenital malformations, and matched controls were measured, as were levels in sera from their mothers. Neonates with NTD had significantly lower serum IgG levels than 22 control neonatal sera. On the other hand, the mothers of these neonates with NTD had elevated serum IgG levels resulting in a striking imbalance in the mother/neonate IgG ratio. In contrast to IgG, IgM levels in maternal and neonatal sera from the NTD group were within normal values. The maternal albumin levels were however significantly increased reflecting hemoconcentration. In sera from 3 neonates born with other congenital malformations (hydrocephaly, caudal appendage and sacral tumor) the only significant changes were higher IgM levels and lower mother/neonate IgM ratios. These results are discussed in the context of materno-fetal immune responses, placental transfer of plasma proteins and the possible involvement of immunoglobulins in fetal malformation.     

Maternal serum total cortisol levels in normal and pathologic pregnancies

The effect of pregnancy on maternal serum total cortisol (MSFT) was studied systematically in the course of 90 normal pregnancies (n = 204). Moreover, the evaluation of MSFT determinations in abnormal pregnancies, intrauterine growth retardation (IUGR) and obstetrical complications, premature rupture of the membranes (PROM), premature delivery (PD), and full term pregnancies with post maturity syndrome (PMS) were also investigated. MSFT was measured by an enzyme immunoassay. Gradual increase in MSFT was found from the 6th week of pregnancy to the 40th week of pregnancy and a sharp rise was noted during the last 2 weeks before the onset of labor (P less than 0.002). In IUGR, MSFT was significantly lower (P less than 0.001). In the cases of PROM and PD, MSFT was highly elevated (P less than 0.0001), independently of the gestational age. In pregnancies with well documented PMS, MSFT was much lower than in normal full term pregnancies with even a downward trend in serial determinations (P less than 0.0001).     

Salivary oestriol in normal and abnormal pregnancies

Summary. Profiles of daily salivary oestriol concentrations throughout the third trimester of pregnancy have been constructed for 14 normal and 11 abnormal pregnancies. Day-to-day variations were significantly higher than those reported for unconjugated oestriol in plasma or serum. A sustained decline in salivary oestriol concentrations was observed in one pregnancy in which intrauterine death occurred. Sustained falls were also observed in two pregnancies in which a healthy infant was born at term. In all other patients a normal salivary oestriol profile correlated with a favourable outcome. Salivary oestriol measurements provide similar information to plasma unconjugated oestriol measurements while offering the advantages of a simple, non-invasive sample collection procedure.     

Maternal serum CA125 levels in early intrauterine and tubal pregnancies

Summary Using an immunoradiometric assay, serum CA125 levels were measured in 13 women with a normal pregnancy, 9 with a spontaneous abortion, 3 with a hydatidiform mole, and 15 with a tubal pregnancy. Serum CA125 levels were high in patients with a normal pregnancy (154±169 U/ml; mean±S.D.), a spontaneous abortion (244±258 U/ml), or a hydatidiform mole (54±16 U/ml). In contrast, CA125 levels in patients with a tubal pregnancy (33±25 U/ml) were low, and almost all of those without uterine bleeding (25±9 U/ml) were within the normal range for non-pregnant women (<35 U/ml). The difference between serum CA125 levels with intrauterine pregnancy and with tubal pregnancy may be ascribed to the difference of the amount of decidual tissues at the site of trophoblastic invasion.     

Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies.

Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies.     

Maternal cytoglobin (CYGB) serum levels in normal and preeclamptic pregnancies

Objective: To investigate cytoglobin levels in women with preeclampsia and women with uncomplicated pregnancies.

Materials and methods: A cross-sectional study including 26 pregnant women complicated with early-onset preeclampsia (EO-PE) and 26 pregnant women complicated with late-onset preeclampsia (LO-PE) were recruited for the study group. Twenty-seven healthy pregnant women selected randomly were included in the control group. The serum CYGB concentrations were measured using an enzyme-linked immunosorbent assay.

Results: Gestational age at delivery and mean birth weight were significantly lower in the preeclampsia groups than in the control group and were found to be the lowest in the EO-PE group (p?p?p?=?1.000).

Conclusions: Serum CYGB levels were significantly higher in patients with EO-PE and LO-PE as compared to healthy pregnant women.     

Haemoglobin A1c levels in normal and diabetic pregnancies

Serial measurements of the HbA1c levels were performed during pregnancy in 4 groups of patients attending Antenatal Clinics: 36 normal pregnancies; 16 pregnancies in established insulin-dependent diabetic patients; 9 patients with gestational diabetes diagnosed during that pregnancy; and 21 patients who had been diagnosed as having gestational diabetes in at least one previous pregnancy. In the normal pregnancy HbA1c levels showed a small but significant increase from the end of the first trimester to delivery despite blood glucose levels remaining constant throughout. In the insulin-dependent and gestational diabetic patients, blood glucose levels remained significantly higher than in the normal throughout pregnancy but only in insulin-dependent diabetic patients and the newly diagnosed untreated gestational diabetic patients were the HbA1c levels significantly higher than in the normal. In those patients who had previous pregnancies complicated by gestational diabetes, blood glucose levels were significantly higher than in the normal but HbA1c levels were not. This dissociation between blood glucose and HbA1c levels in gestational diabetic pregnancies in particular limits the value of HbA1c levels in monitoring antidiabetic treatment in such pregnancies.     

Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies

OBJECTIVE: To assess the value of ultrasonography and Doppler imaging in characterizing the intervillous circulation in normal and abnormal early pregnancy. DESIGN: Cross-sectional study. SETTING: Tertiary care academic hospital. PATIENT(S): Eighty-five normal pregnancies and 125 missed miscarriages at 7 to 13 weeks of gestation. INTERVENTION(S): Grey-scale ultrasonography was used to evaluate the placental anatomy and detect moving echoes inside the intervillous space, and color power Doppler imaging was used to detect continuous venous-like flow in the placental tissue. MAIN OUTCOME MEASURE(S): Degree of agreement between two investigators for use of grey-scale imaging, comparison of detection of moving echoes in normal and abnormal pregnancies, and comparison of detection of intervillous circulation with grey-scale and color Doppler imaging in abnormal pregnancies. RESULT(S): The overall degree of agreement between the two investigators was good. A significantly different distribution of blood flow was found between normal and abnormal pregnancies at 7 to 9 weeks and 10 to 11 weeks but not at 12 to 13 weeks. Intervillous moving echoes were detected by grey-scale imaging significantly more frequently than an intervillous blood flow was detected with color Doppler imaging. CONCLUSION(S): In early pregnancy failure, there is a premature and diffuse onset of intervillous blood flow that can be detected by grey-scale imaging. This abnormal blood flow pattern may increase the oxidative stress on the early placental tissue and subsequently impair placental development.     

Maternal serum and amniotic fluid levels of macrophage inhibitory cytokine 1 in Down syndrome and chromosomally normal pregnancies

OBJECTIVES: To measure maternal serum and amniotic fluid levels of macrophage inhibitory cytokine-1 (MIC-1) in Down syndrome and normal pregnancies, assessing the utility of MIC-1 as a prenatal marker of Down syndrome. METHODS: Stored serum from 64 Down syndrome and 399 control pregnancies, collected at 8 to 17 weeks of pregnancy, and stored amniotic fluid from 17 Down syndrome and 53 controls, collected at 15 to 19 weeks of pregnancy, were retrieved for analysis. MIC-1 was measured using an established in-house ELISA, blinded to sample type. RESULTS: In maternal serum, MIC-1 levels are not altered in Down syndrome in either the first or second trimester. Levels, expressed as median (95% CI) multiples of the median (MoM), in the Down syndrome cases and controls were 1.07 (0.9-1.1) MoM and 1.0 (0.95-1.03) MoM respectively. In amniotic fluid, MIC-1 levels were significantly decreased compared to controls, 0.52 (0.44-0.64) MoM versus 1.0 (0.85-1.08) MoM (p < 0.0001). CONCLUSION: MIC-1 is decreased in amniotic fluid but not in maternal serum in Down syndrome pregnancies. MIC-1 will not be useful as a prenatal marker of Down syndrome.     

Amniotic fluid glucose values in normal and abnormal pregnancies

Glucose values were determined in 102 urine samples of newborn infants and in 2295 amniotic fluid (AF) samples of women between the 14th and 42nd week of pregnancy. One thousand, six hundred fifty-five of the AF samples derived from normal pregnancies, 50 from pregnancies with fetal malformations, 115 from cases of hydramnios, 246 from pregnant women with an abnormal oral glucose tolerance test, and 230 from insulin-dependent diabetics. Mean AF glucose concentration rises slightly between the 14th and 17th week of pregnancy, decreasing from 46 to about 16 mg% at the end of pregnancy. In cases of fetal malformations, 68% of the glucose levels was below the tenth percentile of normal values. Hydramnios showed no deviation from normal values. In patients with abnormal glucose tolerance, AF glucose increased by a total of 42% and by 67% in fetal hyperinsulinism. Insulin-dependent diabetics had glucose values elevated by a total of 77% and by 106% in fetal hyperinsulinism. The AF glucose profile reflects the level of maternal blood glucose that is transported to the fetus and excreted in the fetal urine as a major source of glucose in AF.