PubMed Health⌕ Search

Biomedical subjects

A M Hagenaars

Publications and source records attributed to A M Hagenaars.

At least 19 recordsLinked to original sources

Adverse obstetric outcome in low- and high- risk pregnancies: predictive value of maternal serum screening.

OBJECTIVE: To determine whether the relationship between adverse pregnancy outcome and elevated maternal serum alpha-fetoprotein (MSAFP) and/or maternal serum hCG levels in women whose fetuses have no chromosomal abnormalities or neural tube defects is restricted to pregnancies with a priori elevated risk for pathology or also present in low-risk pregnancies. METHODS: The outcomes of pregnancy in two groups of patients with elevated MSAFP and/or maternal serum hCG values were compared with the outcomes of a reference group with normal serum values. The first study group consisted of 83 women without pre-existing risk for poor outcome as defined by the guidelines of the Dutch Society of Obstetrics and Gynecology. The second study group consisted of 62 women with a priori elevated risk according to these guidelines. RESULTS: Fetal or neonatal death, pregnancy-induced hypertension, placental abruption, placenta previa, preterm delivery, delivery of infants with birth weights in the 2.3rd percentile, and complications during the third stage of labor occurred significantly more often in patients with elevated values and low a priori risk than in women with normal values and without pre-existing risk factors. There was no significant increase in adverse pregnancy outcome in women with elevated values and high a priori risk compared with women with normal values and elevated a priori risk. CONCLUSION: In women at low risk, elevated MSAFP and/or maternal serum hCG values are predictive of adverse pregnancy outcome. In women with a priori elevated risk, abnormal serum values do not increase this risk.

Adult↗

[Maternal serum screening for Down syndrome and neural tube defects].

OBJECTIVE: Evaluation of maternal serum screening for Down's syndrome (DS) and neural tube defects (NTDs). DESIGN: Longitudinal study. SETTING: Department of Obstetrics and Gynaecology, University Hospital Utrecht, the Netherlands. METHOD: 6362 pregnant women underwent serum screening for DS and (or) NTD between the 15th and 21st weeks of pregnancy between March 1991 and March 1996. Screening was performed using alpha-foetoprotein, unconjugated oestriol, human chorionic gonadotrophin and maternal age. The result of each individual test was a calculated risk for delivering a child with DS and (or) NTD. RESULTS: Nine out of 12 singleton pregnancies of a foetus with DS were detected. To this purpose, 573 women who, according to the serum screening had an increased risk of a child with the abnormality, were offered amniocentesis, which was performed in 471 of them. Two twin pregnancies with a total of 3 DS affected foetuses were also detected; one twin pregnancy of a DS foetus was screen-negative. The one case of spina bifida was screen-positive. The proportion of women eligible for invasive prenatal diagnosis because of maternal age increased from 9% to 25% in the course of the study. Of 1118 women aged > or = 36 years 913 (82%) declined invasive investigation compared with 40% in the general population. CONCLUSION: The results of the maternal serum screening program in Utrecht were comparable with other studies. Maternal serum screening is accepted as an alternative by women above 36 years, and allows to decrease the need for amniocentesis without a significant loss in detection rate.

Amniotic Fluid↗

Maternal serum alpha-fetoprotein in fetal anal atresia and other gastro-intestinal obstructions.

The fetal gastro-intestinal (GI) tract contributes to alpha-fetoprotein (AFP) levels in amniotic fluid and hence to those in maternal serum (MS). This study retrospectively analysed results of second trimester MSAFP screening in cases of fetal GI tract obstruction. 18 cases of fetal GI obstruction were diagnosed amongst 17,036 women who underwent MSAFP screening between 1979 and 1997: seven had oesophageal atresia, four had duodenal atresia, six had anal atresia, and one had both anal and oesophageal atresia. MSAFP in pregnancies of a fetus with anal atresia was significantly lower than the population median. MSAFP in cases of fetal oesophageal or duodenal atresia was low but these differences did not reach significance.

Anus, Imperforate↗

The effect of chorionic villus sampling on the number of fetal cells isolated from maternal blood and on maternal serum alpha-fetoprotein levels.

Fetal cells are present in the circulation of pregnant women and can be isolated using density gradient centrifugation and magnetic cell sorting. In the present study, maternal cell preparations were depleted for CD45- and CD14-positive cells and enriched for CD71-positive cells. The number of fetal nucleated cells was determined using fluorescence in situ hybridization for X and Y chromosomes. Analysis of maternal blood samples taken before and after transabdominal chorionic villus sampling (TA-CVS) showed an increase in the number of fetal cells in 10 out of 19 male pregnancies after the invasive procedure. This cellular transfusion was found to correlate with elevated maternal serum alpha-fetoprotein levels. TA-CVS-induced cellular transfusion may form a good in vivo system to optimize fetal cell isolation procedures and to study fetal cell dynamics and characteristics.

Adult↗

Are Down syndrome fetuses detected through maternal serum screening similar to those remaining undetected?

This study was designed to examine whether fetuses with Down syndrome (DS) identified through serum screening are different from those whose mothers have normal serum screening results. It was a retrospective follow-up study of pregnancies where maternal serum alpha-fetoprotein (MSAFP) concentrations were measured to identify women at increased risk of having a baby with a neural tube defect (NTD). An enhanced risk for NTD was the only reason for intervention in the screened population. Clinical features of fetuses or children with DS were related to the screening results. A retrospectively calculated term risk of 1/250 classified a pregnancy as having been at an elevated risk of DS. The outcome measures were fetal or neonatal death and severe somatic disease. Human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3) were measured retrospectively in frozen samples of the DS pregnancies and the same cut-off level was used for classification (so-called 'triple test'). Ten thousand women were included in the study. Pregnancy outcome was known in 93.5 per cent of the cases. Children with and without anatomic defects were found in all subgroups of test results combinations. All mothers of children with a congenital heart defect (CHD) had a DS risk of > or = 1/250 according to the triple test.

Adult↗

Fetal ductus venosus flow velocity waveforms and maternal serum AFP before and after first-trimester transabdominal chorionic villus sampling.

Doppler flow velocity waveform recording in the fetal ductus venosus and umbilical artery as well as maternal blood sampling for serum alpha-fetoprotein (MSAFP) was performed before and after transabdominal chorion villus sampling (TACVS) in 36 women of advanced maternal age (> or = 36 years). Gestational age ranged between 11 and 13 weeks. No chromosomal anomaly was detected. No statistically significant difference was observed in ductus venosus velocity parameters or in the umbilical artery pulsatility index (PI) before and after CVS in 35 women with a normal pregnancy outcome. One case resulted in fetal loss. Post-CVS median MSAFP levels at 12 weeks (25 kIU/l) and 13 weeks (35 kIU/l) were significantly higher than pre-CVS levels. In three cases, post-CVS MSAFP levels were higher than 600 kIU/l, correlating with feto-maternal transfusions of approximately 1.0-1.4 ml, i.e., of around 40 per cent of feto-placental blood volume. One of these cases displayed absence of fetal peripheral blood flow velocities and fetal bradycardia following TACVS, resulting in fetal loss 1 week later. The remaining two cases had a normal pregnancy outcome, but showed a more than 50 per cent reduction in ductus venosus velocity after TACVS, whereas umbilical artery PI remained unchanged. However, similar velocity changes were associated with only small feto-maternal transfusions. Umbilical artery PI values remained unchanged.

Blood Flow Velocity↗

Maternal serum markers in second-trimester oligohydramnios.

The levels of the maternal serum markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) in 35 pregnant women with early second-trimester oligohydramnios differed from those in a reference population of 1699 singleton pregnancies. Maternal serum AFP levels above the 95th centile of the population distribution were observed in 80 per cent (16/20) of oligohydramnios cases with a normal fetus and in only 20 per cent (3/15) of the cases with a fetus displaying urogenital tract malformations. Elevated levels of hCG (above the 95th centile) and decreased levels of uE3 (below the fifth centile) were encountered in 26 per cent (9/35) and 17 per cent (6/35) of the women, irrespective of the fetal condition. The abnormal profile of the serum markers in early second-trimester oligohydramnios resulted in 57 per cent (20 out of 35) of screen-positive cases for either fetal Down's syndrome or neural tube defects, compared with 8.4 per cent (143 out of 1699) in the reference population.

Chorionic Gonadotropin↗

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.

Amniotic Fluid↗

Maternal serum alpha-fetoprotein levels and fetal outcome in early second-trimester oligohydramnios.

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels were measured. In contrast, normal MSAFP levels were established in only 2 out of the 17 cases without fetal malformations. These data suggest that fetal urine is the major source of elevated AFP in the maternal compartment in early second-trimester oligohydramnios. This is further supported by the lack of any relationship between concentrations of MSAFP non-reactive with Concanavalin A, originating mainly from the yolk sac-derived amniotic fluid AFP pool, and the presence of fetal diuresis. Three out of 26 women had experienced early second-trimester oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence risk for this condition.

Concanavalin A↗

Prenatal diagnosis of spina bifida aperta after first-trimester valproate exposure.

In the context of a prospective study on the adverse effects of anti-epileptic drugs on fetal outcome, we evaluated our experience with prenatal diagnosis by ultrasonography and alpha-fetoprotein (AFP) determination in amniotic fluid. We compared these results with AFP values in maternal serum obtained prior to amniocentesis. From November 1985 to July 1990, amniocentesis at 16-18 weeks of gestation was performed in 267 pregnancies of 237 different women using anti-epileptic drugs. Among 92 pregnancies with maternal valproic acid use, five (including one concordantly affected monozygotic twin-pair) were terminated because of a spina bifida aperta, all prenatally diagnosed by AFP determination and acetylcholinesterase electrophoresis in amniotic fluid. The maternal serum AFP level was raised (> or = 2.5 multiples of the median (MOM) for singleton pregnancies and > or = 4.5 MOM for twin pregnancies) in only two of these five affected pregnancies. We emphasize that maternal serum AFP levels may be unreliable for prenatal screening for fetal neural tube defects in women taking valproate and recommend that amniocentesis and fetal ultrasound examination should be offered directly.

Acetylcholinesterase↗

Transabdominal chorionic villus sampling in the second trimester of pregnancy: feto-maternal transfusions in relation to pregnancy outcome.

Volumes of feto-maternal transfusions (FMTs) in transabdominal chorionic villus sampling (TACVS) in the second trimester of pregnancy were calculated from the difference between maternal alpha-fetoprotein (AFP) concentrations before and 1 h after TACVS. In 50 pregnancies, there existed no correlation between FMT volume and the amount of villi collected or the number of TACVS attempts. The expected risk of fetal exsanguination due to very voluminous FMT could not be substantiated. In one case, immunization could have been the cause of hydrops fetalis, although only a volume of 0.15 ml could be calculated.

Adult↗

Immune reactions in patients with superficial bladder cancer after intradermal and intravesical treatment with bacillus Calmette-Guérin.

The immune reactivity of patients with strongly recurrent superficial bladder cancer was followed after combined intravesical and intradermal bacillus Calmette-Guérin (BCG) immunotherapy. All patients in this study were previously treated without success with intravesical chemotherapy. The BCG treatment regimen consisted of weekly administrations with BCG (RIVM) for six consecutive weeks, both intravesically and intradermally. In this study, sera and peripheral blood leukocytes (PBL) of patients were tested serially. Besides BCG-antigen-specific reactions, e.g. skin reactivity to purified protein derivatives of Mycobacterium tuberculosis (PPD), antibody formation and antigen stimulation of PBL in vitro, non-antigen-specific immune reactivities were also measured, e.g. mitogen response and spontaneous cytotoxic activity of PBL. In addition the antibody response to bladder carcinoma antigens and the cytotoxic activity of PBL for the bladder carcinoma cell line T24 and the natural-killer-sensitive K562 cell line were investigated. The results obtained from the various assays were evaluated for their prognostic value in relation to the length of the tumor-free interval after the BCG treatment. Because sera and PBL were only obtained during the first 6 months after the BCG treatment, the immune reactivity was compared to the clinical results at that same time. At 6 months after therapy 12 out of 40 BCG-treated patients were tumor-free whereas 28 out of 40 showed a recurrence. Skin reactivity to tuberculin PPD was measured in 40 patients during a period of 3-6 months after therapy. Of patients who showed a recurrence of the tumor within 6 months, 48% of them showed a transient response or developed no response at all to PPD. In the group of patients with a longer tumor-free period (n = 10), only one patient lost the response to tuberculin PPD. Although PBL of a limited number of patients were tested, it was observed that the cytotoxicity to the bladder carcinoma cell line T24, and the natural-killer-sensitive K562 cell line increased in a number of the patients (7 out of 14, and 9 out of 14 respectively). Reactivity of PBL to mitogens and subset distribution (ratio T-helper: T-suppressor/cytotoxic) were not influenced by the BCG treatment. Antibody response to mycobacterial antigen was detected in 9 out of 23 patients investigated. Of these 9 patients, 8 belonged to the group with a recurrence of the tumor within 6 months (n = 17). There was no correlation between the skin reactivity and the antibody response to tuberculin PPD.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intravesical↗

Comparison of ELISA and toxin neutralization for the determination of tetanus antibodies.

In a sandwich ELISA for tetanus antibodies, the influence of the tetanus toxoid concentration used for coating microtiter plates has been studied. The antibody levels by toxin neutralization bioassay and by ELISA were studied for a population with known immunization history. By decreasing the tetanus toxoid concentration in ELISA from 5 to 0.2 Lf/ml, a better correlation was found between the ELISA results and the bioassay titers, but sera from recently immunized people still showed high ELISA titers. This phenomenon cannot be ascribed to nonspecific reactions since sera from nonimmunized people are negative in both assays. All sera negative in ELISA had, however, a bioassay titer beneath 0.01 IU/ml.

Antibody Affinity↗

The influence of malaria and gestation on the immune response to one and two doses of adsorbed tetanus toxoid in pregnancy.

The effect of Plasmodium falciparum infection on the response to immunization with tetanus toxoid in pregnancy is of importance because malaria is more frequent and severe in pregnant women. This paper presents the results of a study in west Kenya of the antibody response to an adsorbed tetanus toxoid in primigravidae and multigravidae living under holoendemic conditions. There was no apparent influence of either P. falciparum infection or gestational age on the immune response to one and two doses of adsorbed toxoid. The antibody response in pregnant women with and without malaria was comparable to that in non-pregnant healthy adults. Previous studies of responses to primary immunization schedules in pregnant and non-pregnant women are reviewed.

Antibody Formation↗

A modified ELISA technique for the titration of antibodies to polio virus as an alternative to a virus neutralization test.

An ELISA based on inhibition of antibody binding for the determination of antibodies to polio virus type I is described. F(ab1)2-fragments of bovine antibodies to polio virus type I are used as the capture antibody thus lowering the background staining. A good correlation was found between the poliovirus neutralizing antibody level and the antibody titers as determined by ELISA.

Animals↗

Measurement of O6-ethyldeoxyguanosine and N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene in DNA by high-sensitive enzyme immunoassays.

Antibodies raised in rabbits against the bovine serum albumin conjugates of O6-ethylguanosine and N-(guanosin-8-yl)-N-acetyl-2-aminofluorene have been used to develop a high-sensitive enzyme-linked immunosorbent assay (HS-ELISA) for the quantification of adducts in DNA modified by ethylating agents and N-acetyl-2-aminofluorene. Linear dose-response relations were obtained in the non-competitive HS-ELISA between 0.5 fmol and 50 fmol O6-ethyldeoxy-guanosine per 2.8 microgram DNA, and between 0.1 fmol and 20 fmol N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene per 0.8 microgram DNA. The sensitivity of an ultrasensitive radioimmunoassay was in the same order of magnitude. Modification levels as low as 0.1 mumol of adduct/mol DNA-nucleotides (1: 10(7)) can be detected by each assay.

2-Acetylaminofluorene↗

Amniotic and maternal serum alpha-fetoprotein levels of rats with induced neural tube defects.

During the complete fetal period alpha-fetoprotein (AFP) was quantified in maternal sera and amniotic fluid from control, hypervitaminosis A and trypan blue treated normal rat fetuses, and from exencephalic and spina bifida aperta fetuses. The occurrence of histologic proven open neural tube defects was associated with amniotic fluid AFP levels that were much elevated over those of control and treated normal fetuses and those with closed neural tube defects at nearly the whole fetal period. In combining these results with the earlier reported morphologic data of the same rat fetuses as used in the present study, it is concluded that the elevation of amniotic AFP is caused by leakage of fetal serum through a disrupted and necrotic nervous tissue into the amniotic fluid. This experimental model of induced neural tube defects results in increase of amniotic fluid AFP levels similar to those found in human amniotic fluid in the presence of neural tube defects.

Amniotic Fluid↗