Prostate-specific antigen in amniotic fluid of normal and abnormal pregnancies

Objective: To examine if prostate-specific antigen (PSA) is present in amniotic fluid or maternal serum during pregnancy and if its presence is associated with fetal abnormalities.

Methods: Samples tested included amniotic fluids from 853 pregnant women for whom amniocentesis was performed; 312 nonpregnant women who donated blood; 259 pregnant women who donated blood at various gestational ages. Amniotic fluid or serum PSA was measured with an ultrasensitive time-resolved immunofluorometric procedure. 372 pregnancies were studied for the presence of genotypic or phenotypic fetal abnormalities.

Results: PSA was present in most amniotic fluids; the median PSA concentration increased from gestational week 11 to 22 and stabilized thereafter until delivery. The most prominent PSA concentration change occurred during gestational weeks 13–14. Pregnant women had significantly higher serum PSA concentrations than nonpregnant women; the pattern of serum fSA concentration change during pregnancy was similar to that of amniotic fluid; however, serum PSA concentrations were lower by a factor of 20–40. No association existed between amniotic fluid F'SA and maternal age, gender of fetus, or length of abstinence of mother from sexual intercourse. After gestational week 15, fetuses with trisomy 21 or 18, anencephaly, or renal disorders were associated with low amniotic fluid PSA levels.

Conclusion: Our data suggest that PSA may play a role in fetal development, especially at gestational ages between 13–20 weeks. The diagnostic usefulness of PSA in identifying fetal abnormalities remains to be determined.     

The amnion regulates movement of fetally derived alpha-fetoprotein into maternal blood.

The present investigation documents that, under normal conditions, most fetally produced AFP reaches the maternal circulation via diffusion across the amnion from amniotic fluid. This has been determined by comparing maternal serum AFP levels with amniotic fluid albumin concentrations in paired samples. The proportionally demonstrated between them indicates a proportional, transamniotic exchange of the two proteins, each originating on opposite sides of the amnion. Albumin is known to reach amniotic fluid by transamniotic diffusion from maternal blood. All amnions restrict AFP movement into maternal serum, but some are distinctly more restrictive than others; in such cases, a relatively greater increase in amniotic fluid AFP concentration would likely have to occur from a fetal lesion before being reflected in maternal serum. Inconsistencies found in several paired samples identify that other variables may also influence passage of AFP to the mother.     

Changes in alpha 1-acid glycoprotein serum concentrations and glycoforms in the developing human fetus.

alpha 1-Acid glycoprotein concentrations and reactivity to concanavalin A were measured in maternal and fetal serum and amniotic fluid obtained from 24 women undergoing diagnostic cordocentesis at 20 to 33 wk gestation and in 30 additional fetal sera (19 to 34 weeks gestation). Maternal alpha 1-acid glycoprotein serum levels were five to ten times higher than fetal and amniotic levels. Fetal alpha 1-acid glycoprotein levels were found to increase with advancing gestational age. Using crossed immunoaffino electrophoresis with concanavalin A, alpha 1-acid glycoprotein patterns were identical in maternal serum and amniotic fluid but totally different in fetal serum. The fetal concanavalin A pattern changed progressively during fetal life towards that of the newborn. These data confirm earlier assumptions of fetal synthesis of alpha 1-acid glycoprotein and provide normal reference values for alpha 1-acid glycoprotein in fetal serum. In addition, the specific fetal concanavalin A pattern indicates that the alpha 1-acid glycoprotein glycosylation process during fetal life differs from that in post-natal life.     

The concentration of alpha-1-antitrypsin in cerebrospinal fluid and serum in a series of 40 intracranial tumors.

Forty patients with histologically proved intracranial tumors were submitted to preoperative lumbar and venous punctures. The concentration of alpha-1-antitrypsin in the serum and in cerebrospinal fluid was determined by radial immunodiffusion technique. In the series, both serum and cerebrospinal fluid alpha-1-antitrypsin concentrations are significantly higher than the mean normal values. No statistical differences are observed in serum alpha-1-antitrypsin levels between benign and malignant tumors, but cerebrospinal fluid alpha-1-antitrypsin is significantly increased in the group of malignant tumors if cases undergoing steroid treatment are excluded. The diagnostic value of alpha-1-antitrypsin determinations in groups of patients with intracranial tumors is suggested.     

Cocaine and metabolite concentrations in the fetal guinea pig after chronic maternal cocaine administration.

To determine the disposition of cocaine (COC) and metabolites after chronic COC exposure in the late gestation guinea pig, six time-bred Dunkin-Hartley guinea pigs were given 10 daily 6 mg/kg COC s.c. injections from day 50 of gestation. Maternal blood and urine, fetal cord blood, and brain and amniotic fluid were collected 1 hr after the last injection. There was no difference between maternal and fetal plasma COC concentrations. This may be due to the combined effect of lower protein binding and ion trapping of COC in the fetus. Benzoylecgonine was higher in maternal plasma, but benzoylnorecgonine was higher in fetal plasma. COC brain-to-plasma ratios were similar in the dam and fetus. Benzoylecgonine was the only metabolite that could be detected in the brain, but levels were too low to quantitate. COC accumulated 3 to 4 times plasma concentrations in the amniotic fluid and was directly proportional to fetal plasma COC concentrations. Benzoylnorecgonine in amniotic fluid accumulated to 2 times fetal plasma levels. The in vitro half-life of COC in amniotic fluid was 30 times longer than plasma elimination half-life in vivo. The high level and long duration of COC in amniotic fluid serve as a reservoir for prolonged fetal COC exposure.     

Pharmacokinetics and pharmacodynamics of labetalol in the pregnant sheep.

The maternal-fetal disposition of labetalol, a combined alpha-1 and beta adrenergic blocker, and its pharmacodynamics in pregnancy are not well understood. This study describes the pharmacokinetics, cardiovascular and metabolic effects of labetalol in the mother and in utero fetus after a 100-mg maternal i.v. bolus administration, in the chronically instrumented pregnant sheep. Labetalol shows a triexponential decline in the mother with a total body clearance of 30.8 +/- 3.83 ml/min/kg, an apparent steady-state volume of distribution (nonparametric) of 3.02 +/- 0.18 liters/kg and terminal elimination half-life of 2.79 +/- 0.66 hr. These estimates are similar to the reported values in pregnant women. Labetalol rapidly crosses the sheep placenta. The peak fetal plasma concentration was 33.7 +/- 5.8 ng/ml, the fetal exposure to labetalol as calculated by the fetal to maternal area under the curve ratio was 14.37 +/- 1.54% and the apparent fetal elimination half-life was 3.71 +/- 0.5 hr. Labetalol persists in the amniotic and fetal tracheal fluids up to 24 hr with concentrations reaching 2- to 4 times the fetal plasma concentration. Whereas there were no significant maternal or fetal cardiovascular effects, some very significant metabolic effects were observed, including fetal and maternal lactic acidosis and hyperglycemia. Lactic acid accumulates in the fetal blood and amniotic fluid with peak concentrations (6.0 +/- 0.31 and 5.5 +/- 0.26 mM, respectively) showing a more than 300% increase over control values. The exact mechanism by which labetalol causes these metabolic effects is not clear, but it may involve its partial beta-2 agonist activity.     

Human serum Zn-alpha2-glycoprotein in amniotic fluid

Human serum Zn-alpha2-glycoprotein (Zn-alpha2-GP) was found to be present in the amniotic fluid in the mean concentration of 0.98 +/- 0.40 mg/100 ml, which represents about one-tenth of its concentration in the maternal serum (9.65 +/- 1.18 mg/100 ml). Its concentration in the amniotic fluid was proportional to the amniotic fluid total protein and very approximately to the maternal serum Zn-alpha2-GP. The relationship between the maternal serum Zn-alpha2GP and the maternal serum total protein as well as between the amniotic fluid total protein and the maternal serum total protein was found to be not significant. The amniotic fluid Zn-alpha2-GP as well as the amniotic fluid total protein showed some increase during gestation to reach the highest values at the end of the second trimester. At present both the origin and significance of the amniotic fluid Zn-alpha2-GP are not known.     

Study of soluble proteins from human amniotic fluid by fraction chromatography (author's transl]

The nature and origin of soluble proteins from human amniotic fluid have been investigated by gel filtration chromatography on Sepharose 6B and ion-exchange chromatography on Ecteola-cellulose. Each fraction has been studied by immunoelectrophoresis. Specific antisera against serum proteins, amniotic fluid proteins, fetal proteins and salivary proteins have been used. These various antisera showed that the amniotic fluid contains maternal proteins, but also more specific proteins from fetal origin such as beta2-microglobulin, urinary mucopolysaccharides, salivary proteins and carcinoembryonic antigen. These results not only confirm that amniotic proteins are essentially from maternal origin, but prove the important fetal contribution and emphasize the importance of the fetoplacental unit in the monitoring of high risk pregnancies.     

Tobramycin: Maternal-Fetal Pharmacology

To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration of TBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 μg/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 μg/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 μg/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation of the fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 μg/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharmacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.     

Alpha-1-antitrypsin content in the serum, alveolar macrophages, and alveolar lavage fluid of smoking and nonsmoking normal subjects.

The content of alpha-1-antitrypsin in the serum, alveolar lavage fluid, and alveolar macrophages of smokers and nonsmokers was studied. Bronchoalveolar lavage was used to obtain alveolar fluid and macrophages from normal volunteers, and alpha-1-antitrypsin and albumin were measured using the electroimmunodiffusion technique. The serum level of inhibitor was not different between the two groups, while the total lavage fliud content of alpha-1-antitrypsin was increased in the smokers. The level of alpha-1-antitrypsin was also significantly greater (P less than 0.001) in the alveolar macrophages of the smokers suggesting the possibility of chronically increased alveolar levels in the cigarette smoker as a possible protective mechanism against proteolysis.     

Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum.

The penetration of ceftriaxone into the fetus at parturition was studied in 17 subjects. Despite its high protein binding, ceftriaxone quickly reached the umbilical cord blood, amniotic fluid, and placenta, achieving substantial concentrations, which then disappeared, with elimination half-lives of approximately 6 h, identical to that of the mother. The elimination half-life of ceftriaxone of 5 to 6 h in these mothers was somewhat shorter than that reported for normal subjects. The concentrations of ceftriaxone achieved in fetal tissues were sufficient for therapeutic effects. The penetration of ceftriaxone into milk was studied 3 days postpartum in 20 other patients. This antimicrobial agent entered breast milk rapidly and disappeared with a half-life of 12 to 17 h. The concentrations achieved were only 3 to 4% of those in maternal serum and were most likely of little clinical relevance.     

Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury.     

人类白细胞抗原-G与胎膜早破关系的研究

目的探讨人类白细胞抗原-G(HLA-G)与胎膜早破(PROM)关系及临床意义。方法随机选取2011年7月至2013年7月临产前行剖宫产分娩的初产妇,检测肘静脉血、羊水及胎膜,分为正常完好胎膜组、足月胎膜早破组和足月前胎膜早破组。应用双抗体夹心酶联免疫吸附实验测定组对象血清、羊水中HLA-G的浓度,比较各组间的相关性。结果正常完好胎膜产妇体内的HLA-G水平以及表达率均比胎膜早破产妇高,并且无感染的正常妊娠产妇胎膜的HLA-G表达率明显比亚临床感染要高,两者经检验均具显著性差异(P0.05)。结论 HLA-G在胎盘中的低表达可能与孕妇感染有关,而HLA-G在胎盘中的低表达可能又与胎膜早破的发生有关,这对于HLA-G在PROM上的研究有着非常重要的意义。     

Typing of Fetal Cells Obtained by Amniocentesis

In 38 of 287 amniocenteses done at the Mayo Clinic the amniotic fluid contained enough erythrocytes to permit blood typing with commercial sera. Simultaneous use of both an acid-elution technic and the direct Coombs test helped to establish three of the four possibilities for having erythrocytes in bloody amniotic fluid: 1) maternal and fetal erythrocytes of different blood types; 2) maternal erythrocytes only; 3) fetal erythrocytes only; and 4) maternal and fetal erythrocytes of the same blood type. Twenty of the 38 bloody amniotic fluids permitted fetal erythrocyte-typing that was later verified postnatally in the living newborns. Traumatic amniocentesis in an Rh_o(D)-negative mother with an Rh_o(D)-positive fetus increases the risk of anamnestic rise in maternal antibody levels. Amniotic epithelial cells from seven different nonbloody amniotic fluids were typed by mixed agglutination technic. Although the ABO groupings were accurate as shown by postnatal typing, Rh_o(D) typing was unreliable.     

Maternal serum and amniotic fluid levels of human placental lactogen in gestational diabetes

Abstract. Human placental lactogen (hPL) levels were measured radioimmunologically in maternal serum and in amniotic fluid between the 37th and 39th weeks of gestation in sixteen gestational diabetic and thirty normal pregnant women. There was no significant difference in maternal serum hPL levels between diabetic (6.1 μ g/ml) and normal pregnant women (6.4 μ g/ml). In contrast, the diabetic group was found to have significantly ( P< 0.001) higher concentrations of amniotic fluid hPL (1.2 μ g/ml) than normal pregnant women (0.8 μ g/ml).     

Exchange of carbon dioxide in the pregnant rhesus monkey: multicompartmental analysis of carbon dioxide kinetics

The exchange of carbon dioxide in the pregnant rhesus monkey has been studied quantitatively using sodium bicarbonate-(14)C and applying the model of a system of seven compartments. The transfer rates among the various compartments, compartment sizes, and the rate of production of carbon dioxide by fetus and mother were determined with a computer programmed to fit the theoretical model to the data by adjusting the parameter values of the model until a "best fit" was obtained. It was confirmed that the exchange of carbon dioxide between fetal and maternal blood across the placenta is rapid, that between fetal blood and amniotic fluid is slow, and that there is no appreciable exchange between maternal blood and amniotic fluid. The mean net production of CO(2) by fetus was 0.476 +/-0.0402 mmoles/kg.min, and that by mother was 0.373 +/-0.0279 mmoles/kg.min.     

羊水乳酸值对胎儿窘迫的预测价值

目的:探讨足月胎儿临产时的羊水乳酸水平对胎儿窘迫的预测价值。方法:收集2006年4月~2010年1月在我院阴道分娩的孕37~41+6足月单胎头位产妇,临产前B超胎儿发育正常,将产程中出现不良胎监图形130例和羊水粪染87例作为观察组,将产前正常胎监图形、羊水清且有良好结局的新生儿240例作为对照组,测定羊水乳酸水平,同时采脐血做血气分析。结果:羊水Ⅰ度及Ⅱ度粪染而胎儿监护正常的病例,其羊水乳酸值与对照组比较,差异无显著性意义(P>0.05),羊水Ⅲ度粪染的羊水乳酸值水平明显升高(P<0.05)。观察组发生胎儿窘迫及新生儿窒息的病例,其羊水乳酸水平明显高于对照组(P<0.05)。结论:胎儿缺氧时羊水乳酸水平升高,对诊断胎儿窘迫有一定的价值。     

妊娠期妇女感染HPV对产妇和胎儿的影响

目的分析妊娠期妇女感染人乳头瘤病毒(HPV)对产妇和胎儿的影响。方法选取116例感染人乳头瘤病毒的产妇作为实验组,另选取健康孕妇116例为对照组,分别对产妇分娩时羊水、胎盘组织及胎儿脐静脉血、口咽部分泌物与外阴分泌物中的HPV进行检测,分析产妇HPV的感染分型。随访1年,观察HPV感染对产妇和胎儿的影响。结果实验组中单型HPV感染及高危型HPV感染的患者所占比例较大,分别为66.38%和76.72%;患者宫颈肉眼形态异常炎症、细胞学检验呈鳞状上皮病变是感染HPV的危险因素;2组患者在分娩方式、产后出血及胎儿生长受限等方面比较,差异无统计学意义(P0.05);正常阴道分娩与剖宫产分娩的胎儿在羊水、胎盘组织及脐静脉血、口咽部分泌物、外阴分泌物或包皮分泌物中的HPV阳性检出率比较无显著差异(P0.05);胎儿HPV感染率为24.14%。结论单型HPV感染及高危型HPV感染是妊娠期妇女HPV感染的主要分型。     

Adiponectin and leptin in maternal serum, cord blood, and breast milk

BACKGROUND: The presence of the adipokines adiponectin and leptin in cord blood and placental and fetal tissues suggests a possible role in fetal development. METHODS: We measured concentrations of adiponectin and leptin in maternal serum, cord blood, and breast milk and examined their correlations within a large, population-based study. Between November 2000 and November 2001, we recruited all mothers and their newborns after delivery at the University of Ulm (Ulm, Germany). The current analysis included 766 mothers with available breast milk samples collected 6 weeks postpartum. Adipokine concentrations were measured with commercially available ELISAs (R&D Systems). RESULTS: Median adiponectin concentrations in maternal serum (n=713), cord blood (n=709), and breast milk (n=766) were 8.6 mg/L, 30.6 mg/L, and 10.9 microg/L, respectively. Median leptin concentrations were 12.8 microg/L in maternal serum, 7.8 microg/L in cord blood, and 174.5 ng/L in breast milk. Whereas increases in leptin concentrations with increasing birth weight, birth weight according to gestational age, and ponderal index were statistically significant in cord blood (all P values<0.0001), cord blood adiponectin was clearly related only to birth weight (P=0.0004). Concentrations of both adipokines were moderately correlated in breast milk and maternal serum (both Spearman rho values were 0.43; P<0.0001). CONCLUSIONS: Concentrations of adiponectin and leptin vary strongly in maternal serum, cord blood, and breast milk, with only moderate correlations between both adipokines in maternal serum and breast milk. The health implications of these patterns warrant further investigation.     

Effect of parenteral nutrition on serum proteins in patients with Crohn disease

The concentration of 19 serum proteins was determined by radial immunodiffusion in 23 patients with Crohn's disease before and after treatment with parenteral nutrition. The results were related to body weight and Crohn's Disease Activity Index. An increased serum concentration of retinol-binding protein, prealbumin, and transferrin paralleled an increase of body weight. Alpha-1-glycoprotein, alpha-2-chymotrypsin, alpha-1-antitrypsin, C-reactive protein, and haptoglobin decreased during parenteral nutrition and showed a positive correlation to the Crohn's Disease Activity Index. The determination of certain proteins is clinically useful, since their serum concentration reflects the influence of parenteral nutrition on nutritional status and disease activity. Measurement of these proteins provides a useful guide to the management of patients with Crohn's disease treated with parenteral nutrition.