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Biomedical subjects

K Nicolaides

Publications and source records attributed to K Nicolaides.

At least 73 records · Page 4Linked to original sources

Antenatal management of severe feto-maternal alloimmune thrombocytopenia: HLA incompatibility may affect responses to fetal platelet transfusions.

In feto-maternal alloimmune thrombocytopenia (FMAIT), severe hemorrhage, particularly intracranial haemorrhage (ICH), may occur before delivery. Management strategies to prevent ICH in high-risk pregnancies include maternal administration of intravenous Ig with or without steroids and fetal platelet transfusions. This report describes a patient who lost three fetuses with ICH because of FMAIT due to anti-HPA-1a. ICH occurred earlier in successive pregnancies (at 28, 19, and 16 weeks of gestation) despite maternal treatment with intravenous Ig and steroids from 14 weeks of gestation in the third pregnancy. The fourth pregnancy was managed by administering weekly intraperitoneal injections of Ig to the fetus from 12 to 18 weeks of gestation. At 18 weeks, there was no evidence of ICH, but the fetal platelet count was only 12 x 10(9)/L. Serial fetal platelet transfusions were started, but there were poor responses because of immune destruction of the transfused platelets by maternal HLA antibodies. There were improved responses to transfusions prepared from the mother and from HLA-compatible HPA-1a-negative donors. At 35 weeks of gestation, a normal infant was delivered by Caesarean section after 20 platelet transfusions. There was prolonged thrombocytopenia in the baby for 15 weeks after birth, probably due to transfer of HPA-1a antibodies in the transfusions of unwashed maternal platelets. The optimal management of pregnancies likely to be severely affected by FMAIT is still evolving. Intensive management was successful in this case, but a successful outcome cannot be guaranteed in severely affected cases. This is the first time that HLA incompatibility has been found to complicate fetal transfusion therapy.

Adult↗

Fetal biophysical profile score. VI. Correlation with antepartum umbilical venous fetal pH.

OBJECTIVE: Our objective was to determine the relationship, if any, between the fetal biophysical profile score and antepartum umbilical venous pH. STUDY DESIGN: This was a prospective observational study conducted concurrently in two centers and involving two discrete high-risk groups of fetuses. Fetal biophysical profile scores were compared with umbilical venous pH values measured in blood obtained by immediate cordocentesis. A total of 493 paired observations of biophysical profile score and pH were made; 104 observations were of fetuses with intrauterine growth retardation and 389 observations were of fetuses with alloimmune anemia. RESULTS: In both data sets there was a highly significant linear correlation between biophysical profile score and umbilical venous pH. Poor biophysical profile score performance (a score of 0 of 10) was always associated with a pH < 7.20, whereas the pH was always > 7.20 when the biophysical profile score was 10 of 10. Sequenced sensitivity of short-term biophysical variables in the detection of acidemia was observed. CONCLUSION: The fetal biophysical profile score accurately predicts antepartum umbilical venous pH.

Analysis of Variance↗

Evaluation of the fetal assessment score in pregnancies at risk for intrauterine hypoxia.

OBJECTIVE: Our purpose was to define the diagnostic value of a new fetal assessment score that is based on each of the components of the Apgar score. STUDY DESIGN: A fetal assessment score was established to study the main fetal vital functions: (1) cardiovascular (heart rate, color of the skin in the Apgar score), now based on fetal heart rate patterns and Doppler assessment of fetal blood flow redistribution, (2) fetal respiratory (quality of breathing in the Apgar score), now based on Doppler assessment of uteroplacental perfusion, and (3) neuromuscular function (tone and reflexes in the Apgar score), now based on fetal tone and response to external stimuli. The fetal assessment score was used in the study of 110 postdate pregnancies and 103 small-for-gestational-age infants and was compared with the traditional biophysical profile score in the prediction of perinatal outcome. RESULTS: There were significant associations between both the fetal assessment score and the biophysical profile score with fetal distress that necessitated operative delivery, low Apgar scores, and low umbilical cord arterial blood pH. However, receiver-operator characteristic plots demonstrated that the fetal assessment score was superior to the biophysical profile score in predicting fetal distress and low Apgar values particularly in the small-for-gestational-age infants. The best single parameters in predicting fetal distress were the amniotic fluid volume in the biophysical profile score and fetal heart rate patterns and pulsed Doppler measurements in the new score. CONCLUSION: A fetal Apgar score in which respiration is assessed by placental perfusion rather than chest movements and in which skin color is assessed by centralization of fetal blood flow may be better than the traditional biophysical profile score in predicting fetal hypoxic compromise.

Apgar Score↗

Interactions between the embryo and corpus luteum.

A total of 102 patients who had become pregnant following in-vitro fertilization (IVF) and embryo transfer were studied at weekly intervals between 4 and 14 weeks gestation. The pregnancies were classified as follows: (i) normal singleton, n = 52; (ii) normal twin, n = 24; (iii) heterotopic, n = 4 (weeks 4-8 only); and (iv) anembryonic with a viable intra-uterine singleton, n = 22. The serum concentrations of human chorionic gonadotrophin (hCG), Schwangerschaft protein-1 (SP-1) and pregnancy-associated plasma protein-A (PAPP-A), oestradiol and progesterone were measured. The mean serum concentrations of HCG, SP-1 and PAPP-A were significantly less in heterotopic than in singleton, singleton/anembryonic or twin pregnancies (P < 0.01-0.05), while those of progesterone and oestradiol were not different at any time. There were no significant differences between the serum concentrations of any of the substances analysed in singleton/anembryonic and singleton pregnancies, but the concentrations of all the substances analysed were significantly greater in twin pregnancies from as early as 7 weeks (P < 0.01-0.05). These data show that in heterotopic pregnancies trophoblast function is reduced, as suggested by the lower concentrations of the placental proteins. Despite this the concentrations of oestradiol and progesterone, derived predominantly from the corpus luteum between 4 and 8 weeks, are equivalent to those found in twin pregnancies, and greater than those found in singleton and singleton/anembryonic pregnancies. These findings support the notion that although HCG may rescue the corpus luteum it does not subsequently have a direct effect on its function, and suggest that the embryo may influence corpus luteum function.

Chorionic Gonadotropin↗

Abnormal fetal immunological development in Down's syndrome.

OBJECTIVE: To investigate the intrauterine development of the immune system in Down's syndrome. DESIGN: Cross sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, London, UK. SUBJECTS: 16 fetuses with Down's syndrome and 104 fetuses with a normal karyotype at 17-24 weeks gestation. MAIN OUTCOME MEASURE: Flow cytometry was used to enumerate T (CD3+), B (CD19+) and NK (CD3- & CD16+/CD56+) lymphocyte subpopulations in fetal blood obtained by cordocentesis. RESULTS: The median numbers of T, B and NK lymphocytes in fetuses with Down's syndrome (1.52 x 10(9)/l, 0.08 x 10(9)/l, and 0.10 x 10(9)/l, respectively) were significantly lower than in the chromosomally normal fetuses (T lymphocytes: 1.98 x 10(9)/l, z = 3.04, P < 0.01; B lymphocytes: 0.50 x 10(9)/l, z = 5.84, P < 0.0001; and NK lymphocytes: 0.19 x 10(9)/l, z = 3.14, P < 0.01). CONCLUSION: These data demonstrate that in Down's syndrome, there is abnormal intra-uterine development of the immune system.

B-Lymphocytes↗

Fetal anaemia and its relation with increased concentrations of adenosine.

Adenosine concentrations were measured in umbilical venous blood obtained by cordocentesis from 14 fetuses of 19-34 weeks' gestation. The concentration did not change significantly with gestational age, but anaemic fetuses showed significantly increased concentrations of adenosine and there was a positive association with blood oxygen tension. These findings suggest that the fetus responds to tissue hypoxia by increasing blood adenosine concentrations from at least 19 weeks' gestation.

Adenosine↗

Screening for fetal chromosomal abnormalities by maternal serum biochemistry and ultrasound examination of fetal morphology.

The failure of screening studies based on maternal age to reduce substantially the birth incidence of chromosomally abnormal babies has stimulated the search for new methods of screening. In this paper we review the latest literature on the two new approaches to screening for fetal chromosomal abnormalities: maternal blood analysis and examination of the fetal anatomy by ultrasound. Preliminary results from maternal serum biochemistry screening indicate that detection of trisomy 21 is significantly improved, and application of biochemical testing may be expanded to the first trimester of pregnancy. Findings from studies on the association between fetal malformations and chromosomal abnormalities indicate that a high percentage of fetuses with an abnormal karyotype can be detected by ultrasound. In order to improve the detection rate and counsel parents appropriately, prospective studies are needed to determine the sensitivity and specificity of different markers in unselected populations of all ages. Information from such studies will also help us to avoid unnecessary anxiety and keep the fetal loss rate due to invasive procedures as low as possible.

Antigens, Tumor-Associated, Carbohydrate↗

Overexpression of esterase D in kidney from trisomy 13 fetuses.

Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses.

Abnormalities, Multiple↗

Craniofrontonasal dysplasia in two male sibs.

Craniofrontonasal dysplasia (CFND) was diagnosed in a male child who had bilateral coronal craniosynostosis, midline facial clefting with cleft lip and palate, a broad and high forehead, and hypertelorism. The parents were normal and there was no family history suggestive of CFND. A small recurrence risk was counselled and prenatal ultrasound was recommended in the next pregnancy. At 23 weeks, the ultrasound scan detected a number of dysmorphic features and the pregnancy was terminated. Autopsy of the aborted male foetus showed the following features: High arched palate, a sloping forehead, flattened nose and receding chin, multiple joint contractures, particularly of the mid phalangeal joints, elbows and ankles. This report highlights the occurrence of CFND in two male siblings born to normal parents, and therefore the need to perform prenatal ultrasound in a subsequent pregnancy, even if CFND is diagnosed in an isolated case.

Abnormalities, Multiple↗

Haemophilia: strategies for carrier detection and prenatal diagnosis.

In 1977 WHO published in the Bulletin a Memorandum on Methods for the Detection of Haemophilia Carriers. This was produced following a WHO/WFH (World Federation of Haemophilia) Meeting of Investigators in Geneva in November 1976, and has served as a valuable reference article on the genetics of haemophilia. The analyses discussed were based on phenotypic assessment, which, at that time, was the only procedure available. The molecular biology revolution in genetics during the 1980s made enormous contributions to our understanding of the molecular basis of the haemophilias and now permits precise carrier detection and prenatal diagnosis. WHO and WFH held a joint meeting on this subject in February 1992 in Geneva. This article is the result of these discussions.

Base Sequence↗

Successful outcome after Nd : YAG laser separation of chorioangiopagus-twins under sonoendoscopic control.

Endoscopic laser coagulation of the chorioangiopagus was successfully performed at 25 weeks' gestation in a pregnancy presenting with acute polyhydramnios due to twin transfusion syndrome. Under local anesthesia, a rigid fetoscope housed in a 2.7 mm diameter cannula was introduced transabdominally into the amniotic cavity and the communicating vessels were coagulated by Nd : YAG laser through a fiber that was passed down the side-arm of the cannula. There was rapid normalization of urine output in both fetuses and resolution of the oligo- and polyhydramnios in the donor and recipient twins, respectively. Furthermore, there was normalization in both fetal circulations, as assessed by Doppler velocimetry, and there was gradual resolution of the hydrops in the recipient. Two healthy babies were born 9 weeks after the procedure.

Journal Article↗

Randomized study of early amniocentesis versus chorionic villus sampling: a technical and cytogenetic comparison of 650 patients.

In a prospective randomized trial of 650 patients at 10-13 weeks' gestation, early amniocentesis was compared to chorionic villus sampling (CVS) for successful sampling and cytogenetic results and the speed with which results can he obtained. The indications for fetal karyotyping were advanced maternal age, parental anxiety or a family history of chromosomal abnormality in the absence of a balanced parental translocation. At early amniocentesis, 10 ml of amniotic fluid were successfully obtained in all 324 cases, in 320 (98.8%) at the first attempt and in four cases (1.2%) after two needle insertions. CVS provided sufficient material for cytogenetic analysis in 314 of 326 (96.3%) cases at the first attempt and in nine (2.8%) after two needle insertions; in three cases only maternal tissue was obtained and subsequently early amniocentesis was performed. Cell culture and chromosomal analysis were successful in 318 of 324 (98.1%) cases of early amniocentesis and in 321 of the 323 (99.4%) cases of CVS where villi were obtained. The median interval between sampling and successful result from cell culture was 12 days for early amniocentesis and 11 days for CVS. Mosaicism was detected in five cases of CVS but in none of the early amniocenteses; three of these cases were confirmed as true fetal mosaics. This study illustrates that early amniocentesis is a viable alternative to CVS for first-trimester fetal karyotyping. The results of the continuing prospective 1 trial will establish the safety and cytogenetic accuracy of the two techniques.

Clinical Trial↗