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OBJECTIVE: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. The aim of this study was to determine preliminary the medians of pregnancy-associated plasma protein A (PAPP-A) in the first trimester of pregnancy and to compare PAPP-A with other biochemical markers used for biochemical prenatal screening. DESIGN: Retrospective study. SETTING: First Institute of Medical Chemistry and Biochemistry and Institute for Clinical Biochemistry, First Medical Faculty, Charles University. Institute for Care of Mother and Child, Prague. PATIENTS: One hundred forty one pregnant women, who undergo biochemical prenatal screening for chromosomal disorders between 7th and 13th week were studied. In addition six women in the second trimester and five women with twin pregnancies, two cases of trisomy 21 and one case of trisomy 18 in second trimester were available for study. METHODS: Maternal serum levels of PAPP-A, human chorionic gonadotropin (hCG) and alfa-1-feto-protein (AFP) were measured using ELISA methods. A single radial immunodiffusion was used to determine trophoblast-specific-beta-1-glycoprotein (SP1). RESULTS: PAPP-A levels increased throughout the first trimester with median 1.8 mg/l in the 7th week to 23.0 mg/l in the 13th week of pregnancy. PAPP-A serum levels from 3 women with twin pregnancies were higher than in women with singleton pregnancies. Serum levels of PAPP A in two women with fetus affected by chromosomal disorders did not differ from normal pregnancies. Correlation coefficients between PAPP-A and AFP and between PAPP-A and SP1 were statistically significant (r = 0.42, P < 0.001, respectively r = 0.54, P < 0.001). The levels of PAPP-A and HCG did not correlate significantly (r = 0.019, P = 0.82). CONCLUSION: We established first trimester medians for PAPP-A, which are necessary for evaluation of the pathological values. We found statistically significant correlation between PAPP-A and SP1 and PAPP-A and AFP.

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In utero tracheal occlusion (TO) is a potent stimulus of fetal lung growth, and is currently being applied in clinical trials to treat severe forms of pulmonary hypoplasia. The aim of this study was to examine the effect of timing of TO on pulmonary growth and maturation rates. Fetal rabbits (term = 31 d) were subjected to in utero tracheal clipping at 24 (late pseudoglandular stage) or 27 d of gestation (late canalicular/early terminal sac stage). Sham-operated littermates served as controls (C). Animals were killed at time intervals ranging from 1 to 6 d (early group) or 1 to 3 d (late group) after occlusion. Lung growth was measured by computerized stereologic volumetry and 5'-bromo-2'-deoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein-A and BrdU immunohistochemistry and computer-assisted morphometry. Statistical analysis was performed using unpaired Student's t test. Early TO was followed by an initial 3-d stagnation of growth and subsequently a dramatic acceleration of growth (BrdU-labeling index [LI] 10.1 +/- 0. 6% in TO versus 2.7 +/- 0.5% in C at 29 d, P < 0.001). In contrast, late TO induced an immediate and sustained moderate increase of lung growth (BrdU-LI 2.8 +/- 0.9% in TO versus 1.1 +/- 0.2% in C at 30 d, P < 0.05), associated with relatively more pronounced air-space distension. Whereas late TO caused no significant alterations in type II cell density or proliferation, early TO was followed by a marked increase in type II cell proliferation, paradoxically associated with dramatic reduction of type II cell density after 29 d. The effects of intrauterine TO on fetal lung growth and type II cell kinetics critically depend on the gestational age, and thus on the maturity of the lungs at the time of surgery. These findings have important clinical implications with respect to the timing of fetal interventions aimed at promoting lung growth. The fetal rabbit provides an invaluable model to study the mechanics and age dependency of TO-induced lung growth.

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Placental function in multifetal pregnancies before and after embryo reduction was investigated by measuring maternal serum concentrations of pregnancy associated placental protein-A (PAPP-A) and pregnancy specific beta-1-glycoprotein (SP-1). Three groups of pregnant women were studied following assisted reproduction; groups 1 and 2, were 12 singleton and 12 twin pregnancies respectively, and group 3 comprised 12 women with multifetal pregnancies undergoing embryo reduction. PAPP-A and SP-1 were measured serially at 8-21 weeks gestation. In all pregnancies, maternal serum PAPP-A and SP-1 increased with gestation. In twin pregnancies the mean concentrations of SP-1 were significantly higher than in singletons at all gestations, whereas for PAPP-A, concentrations were similar between these groups. In multifetal pregnancies before embryo reduction, the serum concentrations of both proteins were significantly higher than in twin pregnancies. Following reduction, the concentrations of PAPP-A remained significantly higher than for twins throughout, whereas the concentrations of SP-1 gradually converged towards those of twins; by 19 weeks there was no difference between the means of the two groups. These findings suggest that circulating concentrations of SP-1 reflect total placental mass, which is proportional to the number of live fetuses, whereas the pattern of PAPP-A changes suggests that this protein is produced by the placenta, decidua and other tissues.

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Concentration of orosomucoid, pregnancy associated alpha 2-glycoprotein (alpha 2-PAG), Schwangerschaftsprotein 1 (SP1), placental specific-tissue protein 10 (PP10), placental specific-tissue protein 12 (PP12), alpha 1-Fetoprotein (AFP) were estimated in serum samples of 83 patients with lung cancer of stages II-IV. The proteins were determined by means of the single radial immunodiffusion, the rocket immunoelectrophoresis, the radioimmunoassay and the enzymeimmunoassay. Orosomucoid, PP12 and AFP serum concentrations of the cancer group compared with those of the control group, were increased significantly. Orosomucoid (control group: means = 0.828 g/l; s = 0.301; tumour group: mean = 2.16 g/l; s = 0.862); PP12 (control group: mean = 54.08 micrograms/l; s = 61.70; tumour group: mean = 122.52 micrograms/l; s = 131.16); AFP (control group: mean = 3.05 micrograms/l; s = 3.76; Tumour group: means = 8.29 micrograms/l; s = 17.75). alpha 2-PAG was found only in 37 cases of the tumour group; SP1 in 22 cases. PP10 (control group: mean = 2.25 micrograms/l; s = 0.866; tumour group: mean = 2.503 micrograms/l, s = 1.508). On condition that 2 tested parameters at least were estimated in the pathological range the sensitivity amounted to 0.64 and the specificity to 0.92.

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We measured the serum levels of the pregnancy-associated protein SP-1 by radioimmunoassay in 91 patients with a diagnosis of germ cell testicular cancer. Sixty-seven of the men had active disease, and of these, 52 per cent had elevated levels of SP-1. In contrast, all 24 patients with inactive disease had normal levels. Elevations of SP-1 were associated more often with elevated levels of human chorionic gonadotropin than with elevated levels of alpha-fetoprotein, but elevated SP-1 levels also occurred in patients with normal levels of both of these established tumor markers. We studied serial samples from 21 patients, and in 5 the SP-1 level provided clinically valuable information not provided by the other two markers. SP-1 is a clinically useful marker in germ cell testicular cancer. Further studies are needed to determine the role of the two forms of protein, alpha and beta, and to define the conditions under which the SP-1 level is elevated.

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