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Biomedical subjects

G C Christiaens

Publications and source records attributed to G C Christiaens.

At least 19 recordsLinked to original sources
PubMed2004

[Fetal DNA in maternal blood].

There is a certain degree of foetal-maternal transfusion in every pregnancy. The possibilities for using intact foetal cells extracted from maternal blood for prenatal diagnosis are limited. Recently real-time polymerase chain reaction (PCR) techniques have allowed the identification and quantification of foetal DNA in the maternal blood. Foetal sex determination with Y-chromosome-PCR has been found to have a specificity of 100%. The sensitivity is 96% but increases with gestational age, so that from 10 weeks onwards the sensitivity approaches 100%. In the case of X-linked diseases, this technique can reduce invasive prenatal diagnosis by 50%. In the case of a foetus with an elevated risk for congenital adrenal hyperplasia, early non-invasive foetal sexing can also shorten the period of maternal dexamethasone use so as to prevent virilisation in the female foetus. Early second trimester non-invasive foetal RhD genotyping with an RhD-PCR has a sensitivity and specificity of 100% each. Therefore in the future, anti-D immunoprophylaxis will be superfluous in RhD-negative women with an RhD-negative foetus. Theoretically all new and paternal inherited disorders with a known gene defect can be detected in maternal plasma. Some examples have already been described. Recently published small scale studies describe elevated concentrations of free foetal DNA in maternal plasma in (threatening) preterm labour, pre-eclampsia and aneuploidy. Large-scale studies are necessary to demonstrate the value of these findings.

Chromosomes, Human, X↗
PubMed2001

[Complicated but successful resuscitation after amniotic fluid embolism].

A 33-year-old woman, gravida IV, para III with unexplained polyhydramnios was admitted to give birth at 29 weeks of pregnancy. Directly after the spontaneous breaking of the membranes, asystolia occurred. Following emergency resuscitation the sinus rhythm returned. Upon the relaparotomy due to a large filling requirement and increasing abdomen size, 'crush' lesions to the spleen and liver were visible; following this a splenectomy was carried out and tampons applied to the liver. After seven months the patient had slight residual symptoms; three weeks after his birth her son was transferred in good condition to another hospital. Amniotic fluid embolism is a rare complication of pregnancy with often serious complications for mother and child. The diagnosis is based on the clinical symptoms of cardiac arrest or sudden profound shock, acute respiratory failure, and/or disseminated intravascular coagulation, occurring in most cases during or soon after delivery, in the absence of an alternative cause (in particular primary cardiopulmonary causes). If the clinical picture deviates from the expected post-resuscitation course alternative diagnoses or resuscitation injuries must be considered.

Adult↗
PubMed2001

Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia.

OBJECTIVE: To determine first-trimester fetal sex by isolating free fetal DNA from maternal plasma. METHODS: The index case was a pregnant woman who previously delivered a girl with congenital adrenal hyperplasia. The SRY gene as a marker for the fetal Y chromosome was detected in maternal serum and plasma by quantitative polymerase chain reaction analysis. Simultaneously, we performed the same test in 25 and 19 women in the first and second trimester, respectively, and compared plasma results with fetal gender as assessed by prenatal karyotyping or as seen at ultrasound or birth. RESULTS: In 44 of 45 patients at gestational ages ranging from 8 3/7 to 17 3/7 weeks, we correctly predicted fetal sex using quantitative polymerase chain reaction analysis of the SRY gene in maternal plasma. In one case, the test result was inconclusive. Overall, fetal sex was correctly predicted in 97.8% of cases (95% confidence interval 88.2%, 99.9%). CONCLUSION: Amplification of free fetal DNA in maternal plasma is a valid technique for predicting fetal sex in early pregnancy. In case of pregnancies at risk for congenital adrenal hyperplasia, the technique allows restriction of dexamethasone treatment to female fetuses resulting in a substantial decrease of unnecessary treatment and invasive diagnostic tests.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Comparative genomic hybridization for cytogenetic evaluation of stillbirth.

OBJECTIVE: To ascertain the feasibility and reliability of comparative genomic hybridization for cytogenetic evaluation of macerated stillbirths. MATERIALS: We examined ten stillborn fetuses above 15 weeks' gestation whose karyotypes were unknown because of tissue culture failure. Sixteen fetuses that were successfully karyotyped using prenatal or postnatal tissues were also examined as controls, including five pregnancy terminations with autosomal aneuploidy, one with sex chromosome aneuploidy, one with a chromosomal deletion; five macerated fetuses with normal karyotypes, three with autosomal aneuploidy, and one with sex chromosome aneuploidy and discrepancy between chorionic villi and fetus. RESULTS: All comparative genomic hybridization analyses in fresh and macerated tissues were successful except for one. All normal karyotypes and aneuploidies were confirmed. Comparative genomic hybridization failed in one fetus with a deletion of the short arm of chromosome 18. In the stillborn fetuses without known karyotypes, one aberrant profile was found; however, the results were not confirmed with interphase fluorescence in situ hybridization. In one fetus triploidy was diagnosed with DNA flow cytometry. CONCLUSION: Comparative genomic hybridization is a valuable backup technique for aneuploidy screening in tissues from macerated stillborn fetuses when tissue culture fails. Gains or losses can subsequently be confirmed by fluorescence in situ hybridization, using DNA probes that focus on specific loci of a chromosome.

Aneuploidy↗
PubMed2000

Learning in medicine: chorionic villus sampling.

Operator experience is considered to influence the safety and success of medical procedures. We performed a retrospective survey to assess learning curves in chorionic villus sampling (CVS). Data of 2081 consecutive women, in whom CVS was carried out in a tertiary care university hospital for prenatal diagnosis, were available for analysis. Endpoints of the analysis were fetal loss, failure of the procedure and need for several needle insertions. Frequencies of each endpoint were calculated and plotted for consecutive series of 50 samplings per operator. Logistic regression analysis was used to quantify the effect of operator experience. We observed a statistically significant learning effect for the unit as a whole as assessed by fetal loss figures and the same tendency for need to do several insertions. We did not observe a (collective) learning effect for failure of the procedure. Individual operators showed a significant learning profile for some endpoints. The individual learning profile predominantly depended on previous experience in amniocentesis. Our study substantiates the presence of a learning curve for CVS. This supports the view that centralization and restriction of CVS to a limited number of experienced operators within centres, is likely to have a positive influence on safety and success of the procedure.

Abortion, Spontaneous↗
PubMed2000

The applicability of different PCR-based methods for fetal RHD and K1 genotyping: a prospective study.

The applicability of different PCR-based assays for fetal RHD and K1 genotyping using DNA isolated from uncultured amniotic fluid cells has been tested prospectively: cord blood serotyping served as a control. For RHD genotyping, DNA was amplified with PCRs specific for RHD exon 7, the 3'-non-coding region and intron 4, using standard conditions. The results of these three separate assays were compared to those of a newly-developed multiplex PCR, simultaneously amplifying six regions of RHD. The PCRs analysing the 3'-non-coding region or intron 4 often yielded false-negative results or no results at all. Results of the exon 7 PCR and of the multiplex PCR always corresponded with postnatal serotyping, the multiplex PCR having the advantage of analysing six RHD-specific exons simultaneously. For K1 genotyping, two different PCR-based assays, both analysing the presence of T578C in the KEL gene, were applied. With the first method, a consensus 740-bp product of the KEL gene was amplified and subsequently specifically digested. As we were not able to obtain any PCR product from amniotic fluid DNA, we developed a new K1-specific PCR, amplifying a fragment of 91 bp only in cases of K1-positivity. With this PCR, all K1 genotyping results (n=30) correctly predicted the phenotypes. We conclude that fetal RHD and K1 genotyping can be performed reliably with DNA from uncultured amniotic fluid cells.

Amniotic Fluid↗
PubMed1999

[Prevention, diagnosis and treatment of blood group immunization during pregnancy].

In the Netherlands last year two important policy changes were introduced to prevent haemolytic disease of the newborn: antenatal administration of anti RhD immunoglobulin and screening for antibodies against irregular erythrocyte antigens in all pregnant women. As the predictive value of such antibodies for the detection of hemolytic disease of the newborn is limited, it is uncertain if this measure is really cost-effective. Because blood transfusion is the most important probable cause of the immunization, and because of the clinical severity of anti-K antibodies, it is advised to give exclusively K negative blood to girls and women under the age of 45 years. In addition there is a need for a uniform protocol to deal with women who have been exposed to immunization.

Autoantibodies↗
PubMed1999

[Prenatal typing of Rh- and Kell- blood group system antigens].

Rhesus (Rh) and Kell blood group immunisations are the most frequent causes of haemolytic disease of the newborn. Recently, the molecular bases of the Rh and Kell antigens have been elucidated. Subsequently, specific polymerase chain reactions (PCRs) could be developed to determine the RhD, RhC/Rhc and RhE/Rhe genotypes as well as the KI genotype (from the Kell blood group) with genomic DNA. The tests were applied to genomically determine the foetal Rh and Kell blood groups with DNA obtained from amniotic fluid cells. The genotypes obtained were compared with the Rh phenotypes established by cord blood red cell serology. The PCRs to determine the RhD, Rhc, RhE and Rhe and KI genotypes were found to be reliable. The test for RhC however, resulted in false-positive C genotypes. Indeed, more than half of the subsequently tested C-negative Negroid donors were false-positive with the DNA test. Thus, except for RhC, it is possible to reliably determine the Rh and KI genotypes of a foetus with DNA isolated from amniotic fluid cells. Amniocentesis, however, carries a risk for the pregnancy and therefore the tests will only be justified in pregnant women in whom an antibody has been detected and the father of the foetus is heterozygous for the specific antigen. Recently foetal RhD genotypes were determined in foetal DNA circulating in the plasma of RhD-negative pregnant women. This could eventually lead to the introduction of assays with which the foetal blood group can be determined without any risk to the foetus.

Adult↗
PubMed1999

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↗
PubMed1999

Antiepileptic drug regimens and major congenital abnormalities in the offspring.

To assess the risk of major congenital abnormalities associated with specific antiepileptic drug regimens, a large retrospective cohort study was performed. The study comprised 1,411 children born between 1972 and 1992 in four provinces in The Netherlands who were born to mothers with epilepsy and using antiepileptic drugs during the first trimester of pregnancy, and 2,000 nonepileptic matched controls. We found significantly increased risks of major congenital abnormalities for carbamazepine and valproate monotherapy, with evidence for a significant dose-response relationship for valproate. The risk of major congenital abnormalities was nonsignificantly increased for phenobarbital monotherapy when caffeine comedication was excluded, but a significant increase in risk was found when caffeine was included. Phenytoin monotherapy was not associated with an increased risk of major congenital abnormalities. Regarding polytherapy regimens, increased risks were found for several antiepileptic drug combinations. Clonazepam, in combination with other antiepileptic drugs, showed a significantly increased relative risk. Furthermore, there were significantly increased relative risks for the combination of carbamazepine and valproate and the combination of phenobarbital and caffeine with other antiepileptic drugs. This study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose-response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with phenobarbital.

Abnormalities, Drug-Induced↗
PubMed1998

[The report 'Late termination of pregnancy: caution and assessment' by the consultant group Late Termination of Pregnancy. Consultant Group Late Termination of Pregnancy].

Late termination of pregnancy means terminating a pregnancy after 24 weeks or more following the detection of severe foetal abnormalities, with the aim of bringing about the death of the fetus. According to a recent document on 'Late pregnancy termination: caution and assessment' severe foetal anomalies can be divided into two categories: (a) abnormalities which would inevitably result in perinatal death; (b) abnormalities which lead to severe and irreversible functional disorders, although with a (limited) chance of survival; postnatal life-prolonging treatment only leads to continuation of a hopeless situation for the infant. Category I contravenes the rationale of article 82a of the Dutch Criminal Code which is aimed at providing legal protection for the unborn infant from the moment it becomes viable. Late pregnancy termination in this category should not be considered an offence. Late pregnancy termination regarding category 2 infants could be an offence. However, an appeal based on circumstances beyond the defendant's control, arising from a conflict of duties could lead to nolle prosequi. A case of late termination of pregnancy should be notified as a case of non natural death.

Abortion, Legal↗
PubMed1998

[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↗
PubMed1998

Immune thrombocytopenic purpura in pregnancy.

Of all pregnant women 1.2% have platelet counts below 100 x 10(9)/l. Only a small proportion of these have immune thrombocytopenic purpura (ITP). ITP is caused by antibodies directed against one's own platelets and may affect the mother as well as the fetus. No cases with documented intrauterine fetal bleeding have been reported. The most critical time for the fetus is usually a few days after birth. Hitherto the patient's history has been the best predictor of maternal and neonatal complications. Diagnostic cordocentesis entails a considerable risk and is to be discouraged in most situations. Intrauterine transfusions are effective only for a very limited period. There is no evidence that caesarean section protects the thrombocytopenic infant from intracranial haemorrhage. We therefore recommend restricting caesarean section to obstetric indications and to situations with proven fetal thrombocytopenia and enhanced obstetric risk. The safe cut-off level has yet to be ascertained. It is mandatory to control the newborn's platelet count during the first three days of life.

Female↗
PubMed1997

[Immunology in medical practice. II. Antiphospholipid antibodies in pregnancy].

Antibodies against phospholipids are a risk factor for thrombotic disorders, but also for foetal death, pre-eclampsia, foetal distress and dysmaturity. This group of antibodies (aPLab) includes lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL). These antibodies are encountered in patients with systemic lupus erythematosus (SLE), but also in patients with lupus-like disease and in women with (a history of) symptoms compatible with the antiphospholipid syndrome. Screening for a aPLab is advisable in these patients when they want to conceive and in women with recurrent foetal death after the 12th week of pregnancy. It is not clear if the antibodies exert a direct noxious action or are an accompanying phenomenon. Secondary prevention is possible with acetylsalicylic acid (80 mg/day), if desired in combination with subcutaneous heparin (5000-12,000 units twice daily). The thrombosis prophylaxis should be continued for 6 weeks after delivery.

Antibodies, Antiphospholipid↗