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Biomedical subjects

K Nicolaides

Publications and source records attributed to K Nicolaides.

At least 37 records · Page 2Linked to original sources
PubMed1999

Screening for trisomy 18 by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

In a study of 50 cases of trisomy 18 compared with 947 controls we have found the median multiple of the median (MoM) of maternal serum free beta human chorionic gonadotrophin to be significantly decreased (0.281 MoM) in samples collected between the 10th and 14th week of gestation. Similarly, maternal serum pregnancy associated plasma protein A (PAPP-A) levels are also decreased (0.177 MoM), whilst the median nuchal translucency is significantly higher (3.272 MoM). Free beta-hCG MoM was less than the 5th centile of normal in 64 per cent of cases of trisomy 18 and for PAPP-A was less than the 5th centile in 78 per cent of cases. Also, in 78 per cent of cases the nuchal translucency was above the 95th centile. When combined together in a multivariate algorithm with maternal age, we predict that 89 per cent of cases of trisomy 18 could be detected at a 1 per cent false-positive rate. We conclude that specific trisomy 18 risks should be part of developing risk algorithms combining maternal serum biochemistry and nuchal translucency for use in first trimester screening alongside those for trisomy 21.

Adolescent↗
PubMed1999

The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.

This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.

Female↗
PubMed1999

International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used.

The development of chromosome-specific probes (CSP) and fluorescent in-situ hybridization (FISH) has allowed for very rapid identification of selected numerical abnormalities. We attempt here to determine, in principle, what percentage of abnormalities would be detectable if only CSP-FISH were performed without karyotype for prenatal diagnosis. A total of 146 128 consecutive karyotypes for prenatal diagnosis from eight centres in four countries for 5 years were compared with predicted detection if probes for chromosomes 13, 18, 21, X and Y were used, and assuming 100% detection efficiency. A total of 4163 abnormalities (2.85%) were found including 2889 (69. 4%) (trisomy 21, trisomy 18, trisomy 13, numerical sex chromosome abnormalities, and triploidies) which were considered detectable by FISH. Of these, 1274 were mosaics, translocations, deletions, inversions, rings, and markers which would not be considered detectable. CSP-FISH is a useful adjunct to karyotype for high risk situations, and may be appropriate in low risk screening, but should not be seen as a replacement for karyotype as too many structural chromosome abnormalities will be missed.

Chromosome Aberrations↗
PubMed1998

Maternal and fetal insulin-like growth factors and their binding proteins in the second and third trimesters of human pregnancy.

The insulin-like growth factors (IGFs) are mitogenic polypeptides which circulate bound to a series of at least six binding proteins (IGFBPs). An increasing body of evidence supports a major role for the IGF in the control of human fetal growth although normal values in the human fetal circulation have not been established. In order to provide an accurate reflection of fetal IGFs and IGFBPs in utero, we have sampled fetal blood direct from the umbilical cord at 18-38 weeks of gestation using the technique of cordocentesis. We have measured IGF-I, IGF-II and IGFBP 1-3 in 91 fetuses in order to establish concentrations for these parameters in the second and third trimesters of human pregnancy.

Cordocentesis↗
PubMed1998

Endoscopic laser coagulation in the management of severe twin-to-twin transfusion syndrome.

OBJECTIVE: To assess the clinical effectiveness of endoscopic laser coagulation of placental vessels in the treatment of severe transfusion syndrome. DESIGN: Prospective study. SETTING: Three referral centres for the management of twin-to-twin transfusion syndrome. POPULATION: One hundred and thirty-two pregnancies complicated by severe twin-to-twin transfusion syndrome, reflected by polyhydramnios and enlarged bladder of one twin and oligoanhydramnios and collapsed bladder of the other twin, presenting before 28 weeks of gestation. METHODS: Prospective collection of data on pre-procedure assessment, the procedure and the follow up were collected prospectively. Laser coagulation of placental vessels crossing the intertwin membrane on the chorionic surface under sono-endoscopic guidance, followed by amniodrainage. MAIN OUTCOME MEASURES: Maternal and pregnancy complications, perinatal death and morbidity were assessed over the last five years with follow up of survivors. RESULTS: Endoscopic laser was carried out at a median gestation of 21 weeks. The total number of surviving infants was 144 (55%) and there was at least one survivor in 97 cases (73%). At a minimum age of one year neurological handicap was suspected in six survivors (4.2%). CONCLUSIONS: The results of this multicentre study are similar to those in our original report on the first 45 cases. In comparison with serial amniodrainage, the survival rate may be similar, but the handicap rate in survivors appears much lower. This study stresses the need for a prospective study comparing these two techniques.

Endoscopy↗
PubMed1998

Cerebellar hypoplasia, facial dysmorphism and internal abnormalities: a new recessive syndrome?

Three female sibs had cerebellar hypoplasia, facial dysmorphism comprising a high forehead, lowset posteriorly rotated ears, a prominent upper lip and receding chin, and variable internal abnormalities. Two of the cases had deficient lobulation of the lungs, two had an atrial septal defect of the heart and developmental abnormalities of the urinary system or internal genitalia, one had holoprosencephaly. All had normal chromosomes. This syndrome does not seem to have been reported before and may be inherited in an autosomal recessive manner.

Abnormalities, Multiple↗
PubMed1997

Audit of prenatal diagnosis for haemoglobin disorders in the United Kingdom: the first 20 years.

OBJECTIVES: To audit services for prenatal diagnosis for haemoglobin disorders in the United Kingdom. DESIGN: Comparison of the annual number of cases recorded in a United Kingdom register of prenatal diagnoses for haemoglobin disorders, with the annual number of pregnancies at risk of these disorders, by ethnic group and regional health authority. The number of pregnancies at risk was estimated using data on ethnic group from the 1991 census and data from the United Kingdom thalassaemia register, which records the number of babies born with thalassaemia. SETTING: The three national prenatal diagnosis centres for haemoglobin disorders. SUBJECTS: 2068 cases of prenatal diagnosis for haemoglobin disorders in the United Kingdom from 1974 to 1994. MAIN OUTCOME MEASURES: Utilisation of prenatal diagnosis by risk, ethnic group, and regional health authority. Proportion of referrals in the first trimester and before the birth of any affected child. RESULTS: National utilisation of prenatal diagnosis for haemoglobin disorders was around 20%. During the past 10 years it has remained steady at about 50% for thalassaemias and risen from 7% to 13% for sickle cell disorders. Utilisation for sickle cell disorders varies regionally from 2% to 20%. Utilisation for thalassaemias varies by ethnic group. It is almost 90% for Cypriots and ranges regionally for British Pakistanis from 0% to over 60%. About 60% of first prenatal diagnoses are done for couples without an affected child. Less than 50% of first referrals are in the first trimester. CONCLUSIONS: National utilisation of prenatal diagnosis for haemoglobin disorders is far lower than expected, and there are wide regional variations. A high proportion of referrals are still in the second trimester and after the birth of an affected child. The findings point to serious shortcomings in present antenatal screening practice and in local screening policies and to inadequate counselling resources, especially for British Pakistanis.

Africa↗
PubMed1997

Abnormalities of the heart and great arteries in first trimester chromosomally abnormal fetuses.

Pathological examination of the heart and great arteries was performed in 112 chromosomally abnormal fetuses after surgical termination of pregnancy at 11-16 weeks of gestation. The chromosomal abnormalities were diagnosed by chorion villus sampling which was carried out because screening of the pregnancies by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation identified them as being at increased risk. The group consisted of 60 fetuses with trisomy 21, 29 with trisomy 18, 17 with trisomy 13 and 6 with Ullrich-Turner syndrome. The most common cardiac lesion seen in trisomy 21 fetuses was an atrioventricular or ventricular septal defect. Trisomy 18 was associated with ventricular septal defects and/or polyvalvular abnormalities. In trisomy 13, there were atrioventricular or ventricular septal defects, valvular abnormalities, and either narrowing of the isthmus or truncus arteriosus. Ullrich-Turner syndrome was associated with severe narrowing of the whole aortic arch. In all four groups of chromosomally abnormal fetuses, the aortic isthmus was significantly narrower than in normal fetuses and the degree of narrowing was significantly greater in fetuses with high nuchal translucency thickness. It is postulated that narrowing of the aortic isthmus may be the basis of increased nuchal translucency thickness in all four chromosomal abnormalities.

Abnormalities, Multiple↗
PubMed1997

Coelocentesis: a study of short-term safety.

Coelocentesis was performed in 20 singleton pregnancies at 6-10 weeks of gestation and 2-13 days before planned termination. The control group consisted of 100 women who were also undergoing planned termination and were matched with the study group for maternal age and gestation. During the follow-up period, there were five miscarriages (25 per cent) after coelocentesis and five in the control group (5 per cent) (chi 2 = 6.68; P < 0.01). The high risk of miscarriage following coelocentesis makes the technique unsuitable for early prenatal diagnosis.

Adolescent↗
PubMed1996

Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation.

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder.

Female↗
PubMed1996

Severe fetomaternal alloimmune thrombocytopenia presenting with fetal hydrocephalus.

We report two patients where the finding of isolated fetal hydrocephalus led to the detection of severe fetal thrombocytopenia, using fetal blood sampling. Serological investigation led to the diagnosis of fetomaternal alloimmune thrombocytopenia (FMAIT) due to anti-HPA-1a. Both women had had previous unsuccessful pregnancies probably due to FMAIT; one had had four miscarriages at 17-18 weeks' gestation. The other had had one previous pregnancy complicated by severe fetal anaemia, and eventually hydrocephalus developed and the fetus died without the diagnosis of FMAIT being considered. Subsequent pregnancies in the two women were also affected by FMAIT, but prenatal treatment, predominantly with serial fetal platelet transfusions, resulted in a successful outcome in both cases. These observations suggest that FMAIT should be suspected if there is isolated fetal hydrocephalus, unexplained fetal anaemia, or recurrent miscarriages. The accurate diagnosis of FMAIT is important because recent advances in prenatal management can improve the outcome of subsequently affected pregnancies.

Abortion, Habitual↗
PubMed1996

Pre-term pre-labour amniorrhexis.

In pregnancies complicated by pre-term pre-labour aminorrhexis, there is a risk of intra-uterine infection, which is associated with maternal and perinatal mortality and morbidity. The causes of neonatal death in pregnancies with aminorrhexis are prematurity, pulmonary hypoplasia and sepsis. In the management of pregnancies with pre-term pre-labour amniorrhexis, it is essential to distinguish between those with and without intra-uterine infection. If there is no infection at presentation, it is unlikely that this will develop, and in such cases there is no benefit from hospitalization, bed rest, prophylactic tocolytics or antibiotics. The group with evidence of intra-uterine infection go into spontaneous labour within a few days of amniorrhexis; in this group, the main determinant for the appropriate management is the gestational age at amniorrhexis.

Anti-Inflammatory Agents↗
PubMed1995

Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome.

BACKGROUND: In monozygotic twin pregnancies, there are placental vascular communications between the two fetuses. In 15 percent of such pregnancies there is an imbalance in net blood flow between the twins, resulting in the twin-twin transfusion syndrome. The recipient twin may have severe hydramnios during the second trimester of pregnancy, and there is a high risk of perinatal death and cerebral palsy in survivors. This condition can now be treated by endoscopic coagulation of the vascular anastomoses responsible for fetofetal transfusion with a neodymium:yttrium-aluminum-garnet (Nd: YAG) laser. METHODS: We performed intrauterine surgery in 45 pregnant women carrying twins at 15 to 28 weeks of gestation (median, 21); in each case there was severe hydramnios in one fetus due to the twin-twin transfusion syndrome. With the use of local anesthesia and continuous ultrasound visualization, a rigid fetoscope 2 mm in diameter, housed in a 2.7-mm cannula, was introduced transabdominally into the amniotic cavity of the recipient twin. A systematic search was made for all vessels approaching or crossing the membrane between the twins, and these were coagulated with an Nd:YAG laser by means of a fiber in the side arm of the cannula. RESULTS: Coagulation of the communicating vessels was successful in all cases. The total number of fetuses who survived to delivery was 48 (53 percent), and the number of pregnancies with at least 1 survivor was 32 (71 percent). Among the live-born infants, the median gestational age at delivery was 35 weeks (range, 25 to 40), and the median birth weight was 2098 g (range, 550 to 4252). The median interval between the endoscopic laser procedure and delivery was 14 weeks (range, 0 to 21). All the survivors were developing normally at a median age of 12 months (range, 2 to 24). CONCLUSIONS: Our preliminary experience suggests that the twin-twin transfusion syndrome can be treated effectively by endoscopic laser coagulation of the communicating placental vessels.

Endoscopy↗
PubMed1995

Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies.

BACKGROUND: Doppler studies of the fetal circulation in intrauterine growth retardation and hypoxia have demonstrated a compensatory redistribution of arterial blood flow with increased flow to the cerebrum and myocardium and decreased flow to the periphery. The aim of this study was to evaluate the significance of changes in fetal venous blood flow waveforms in high-risk pregnancies and to investigate the time relation between alterations in venous and arterial Doppler waveform indices in compromised fetuses. METHODS AND RESULTS: The cross-sectional study consisted of 108 high-risk singleton pregnancies between 23 and 42 weeks' gestation without fetal chromosomal abnormalities or major malformations. Blood flow velocity waveforms were recorded from the umbilical arteries, descending thoracic aorta, middle cerebral artery, tricuspid and mitral ventricular inflow, ductus venosus, inferior vena cava, and the right hepatic vein. The mean velocity and pulsatility index were calculated for arterial vessels, the E/A ratio for atrioventricular blood flow, and peak forward velocities during ventricular systole and early diastole, the lowest forward velocity or peak reverse velocity during arterial contraction, and time-averaged maximum velocity for venous vessels. Two ratios for venous waveforms, one of which is the equivalent of the pulsatility index, were calculated. Fetal biophysical assessment was based on a computerized cardiotocogram and the biophysical profile score. The compromised group consisted of 37 fetuses delivered by cesarean section for an abnormal heart rate trace (n = 21) or severe preeclampsia (n = 9) or which died in utero (n = 7) within 10 days of their last Doppler investigation. This group showed significant alterations in arterial and venous flow velocity waveforms but not in atrioventricular inflow. Additionally, to find out whether venous Doppler investigation may help to detect a worsening of the situation in fetuses already showing arterial blood flow redistribution, we analyzed the data of these fetuses separately. The 41 fetuses that had an aorta/middle cerebral artery pulsatility index ratio > 95th percentile were divided into compromised and non-compromised groups according to their biophysical assessment and whether or not they developed fetal distress (cesarean section for abnormal heart rate trace or intrauterine death). The mean values for Doppler parameters of the compromised groups differed significantly from the noncompromised groups in all venous vessels, whereas differences on the arterial side were much less pronounced. Velocity ratios of venous waveforms were significantly higher, and absent or reverse flow in the ductus venosus with atrial contraction indicated a poor prognosis, with a perinatal mortality of 5 out of 8. CONCLUSIONS: Fetal compromise is associated with significant alterations in the fetal arterial and venous circulation. Significant changes in venous Doppler waveforms develop due to increased afterload and perhaps myocardial failure in late deterioration after fetal arterial redistribution is established and seem to be closely related to abnormal biophysical assessment findings. Therefore, Doppler investigation of the fetal venous circulation may play an important role in monitoring the redistributing growth retarded fetus and thereby may help to determine the optimal time for delivery.

Arteries↗