Search PubMed⌕ Search

Biomedical subjects

K H Nicolaides

Publications and source records attributed to K H Nicolaides.

At least 19 recordsLinked to original sources
PubMed2003

First-trimester maternal serum PAPP-A, SP1 and M-CSF levels in normal and trisomic twin pregnancies.

OBJECTIVE: To study PAPP-A and SP1 for biochemical trisomy screening in twin pregnancies and to investigate the role of maternal and placental compartments in marker production by comparing the levels of the decidual cytokine M-CSF with the PAPP-A and SP1 from the placenta. METHODS: Thirteen twin pregnancies with at least one chromosomally abnormal fetus were compared with 68 normal twin pregnancies. Sera were obtained between 11 + 3 and 13 + 6 weeks of gestation, and PAPP-A, SP1 and M-CSF levels were determined by immunoassay. These concentrations were also compared with gestation-matched groups of 18 singleton normal pregnancies and 18 singleton Down syndrome pregnancies. RESULTS: PAPP-A and SP1, but not M-CSF, levels were higher in normal twin pregnancy than in normal singleton pregnancy. SP1 levels, but not PAPP-A, correlated to M-CSF. PAPP-A, but not SP1, levels were reduced in abnormal twin pregnancies, with an increasing effect according to the number of affected fetuses, and were more pronounced in pregnancies with trisomy 18 or 13 than in trisomy 21 fetuses. M-CSF was inconsistent, with a trend towards increased levels in trisomy 21. CONCLUSION: PAPP-A remains the best biochemical screening marker for fetal trisomies 21, 18 or 13, in singleton as well as in twin pregnancy. In contrast to SP1, its site of production is not likely to be restricted to the placenta. The role of the (maternally produced) M-CSF remains to be further investigated.

Adult↗
PubMed2003

Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.

Abnormalities, Multiple↗
PubMed2003

Comparison of color Doppler uterine artery indices in a population at high risk for adverse outcome at 24 weeks' gestation.

OBJECTIVE: To compare uterine artery Doppler velocity and impedance indices in the presence and absence of uterine artery waveform notches, in the prediction of adverse pregnancy outcome in high-risk women. METHODS: One hundred and fifty-seven women identified at Doppler screening as being at 'high risk' underwent a further uterine artery Doppler assessment at 24 weeks' gestation. Pulsatility and resistance indices and minimum, time averaged and time averaged maximum velocities were measured, and the presence of bilateral notches noted. Adverse outcomes were pre-eclampsia, birth weight less than the tenth centile, placental abruption and intrauterine death. The best cut-off for each parameter was assessed by univariate logistic regression, and the comparative performance of the screening parameters was assessed using kappa values. RESULTS: The best performing index in the presence of bilateral notches was mean resistance index, for a cut-off of 0.67, giving a kappa value of 0.65. Mean pulsatility index and lowest pulsatility index performed similarly well, both with kappa values of 0.58. All velocity indices apart from lowest minimum velocity had kappa values of < 0.4. When indices were analyzed, irrespective of notch status, mean resistance and mean pulsatility indices performed similarly, with kappa values of 0.49 and 0.46, respectively; mean minimum velocity had a kappa value of 0.4. CONCLUSIONS: In a high-risk population, uterine artery Doppler mean resistance indices perform better than do velocity indices in the prediction of adverse pregnancy outcome, irrespective of notch status.

Arteries↗
PubMed2002

Monozygotic twins discordant for body stalk anomaly.

We report on two cases of monozygotic twins discordant for body stalk anomaly, diagnosed prenatally in a multicenter ultrasound screening study at 10-14 weeks of gestation. Ultrasound showed a large abdominal wall defect with most of the abdominal contents and almost half of the body in the celomic cavity, in association with severe kyphoscoliosis and a very short umbilical cord. Both pregnancies were managed expectantly and delivered by Cesarean section. The abnormal babies died soon after birth and autopsy confirmed the sonographic diagnosis. Body stalk anomaly in twins is extremely rare. These are, to our knowledge, the first cases reported on monozygotic twins discordant for this anomaly, indicating that the incomplete twinning theory cannot uniformly explain the pathogenesis of the body stalk in twins.

Abdominal Muscles↗
PubMed2002

Platelet changes and subsequent development of pre-eclampsia and fetal growth restriction in women with abnormal uterine artery Doppler screening.

OBJECTIVES: To investigate whether, in women with abnormal uterine artery Doppler, platelet volume and function will identify a subgroup of women at increased risk of pre-eclampsia and intrauterine growth restriction and whether in-vitro platelet aggregation precedes the onset of clinical disease. DESIGN: Platelet number, volume and aggregation induced by collagen or adenosine 5'-diphosphate were evaluated in 16 non-pregnant controls, 29 pregnant women with normal uterine artery Doppler and 31 pregnant women with abnormal Doppler, hence at risk of pre-eclampsia and intrauterine growth restriction at 23 weeks. Outcome of pregnancy was recorded in each case. RESULTS: Twelve women in the group with abnormal uterine artery Doppler subsequently developed pre-eclampsia and/or intrauterine growth restriction. All women with normal uterine artery Doppler had a normal pregnancy outcome. No differences in platelet count or in vitro platelet aggregation induced by collagen were observed between the groups. Mean platelet volume was greater in those with abnormal Doppler who had intrauterine growth restriction or normal pregnancy outcome compared with normal Doppler (10.3 and 10.3 vs. 9.4 fL, P = 0.004 and P = 0.01, respectively). Aggregation induced by adenosine diphosphate was higher in women with abnormal Doppler who developed pre-eclampsia or intrauterine growth restriction compared with those with normal outcomes (66.5 and 66.5 vs. 21%, P = 0.02, P = 0.03, respectively). CONCLUSIONS: Women with abnormal uterine artery Doppler at 23 weeks show alterations in mean platelet volume and platelet function that relate to subsequent adverse outcome.

Arteries↗
PubMed2002

Elective cerclage vs. ultrasound-indicated cerclage in high-risk pregnancies.

OBJECTIVE: To compare pregnancy outcome after elective vs. ultrasound-indicated cervical cerclage in women at high risk of spontaneous mid-trimester loss or early preterm birth. METHODS: This was a retrospective study comparing two management strategies in women with singleton pregnancies who had at least one previous spontaneous delivery at 16-33 weeks of gestation. One group was managed by the placement of an elective cerclage at 12-16 weeks and the other group had transvaginal ultrasound examinations of the cervix at 12-15+6, 16-19+6, and 20-23+6 weeks and cervical cerclage was carried out if the cervical length was 25 mm or less. RESULTS: A total of 90 patients were examined, including 47 that were managed expectantly and 43 treated by elective cerclage. In the expectantly managed group, 59.6% (28/47) required a cervical cerclage. We excluded from further analysis three patients who were lost to follow-up and three because of fetal death or iatrogenic preterm delivery. Miscarriage or spontaneous delivery before 34 weeks' gestation occurred in 14.6% (6/41) of the elective cerclage group, compared with 20.9% (9/43) in the expectantly managed group (chi2 = 0.219, P = 0.640). CONCLUSION: In women at increased risk of spontaneous mid-trimester or early preterm delivery, a policy of sonographic surveillance followed by cervical cerclage in those with a short cervix reduces the need for surgical intervention without significantly increasing adverse pregnancy outcome.

Cerclage, Cervical↗
PubMed2002

Fetal cardiac abnormalities identified prior to 14 weeks' gestation.

OBJECTIVE: An increasing number of patients are presenting at early gestational age as being at high risk for congenital heart disease, as a result of ultrasound screening by nuchal translucency. The feasibility and accuracy of fetal echocardiography was assessed in a series of pregnancies studied before 14 weeks' gestation. METHODS: Echocardiography was attempted in 478 fetuses of crown-rump length 40.0-85.0 mm (median, 60.3 mm) with increased nuchal translucency, suspected abnormalities on routine scan or a family history of heart defect. The findings were related to results of autopsy, karyotyping, later scans and postnatal follow-up. RESULTS: Satisfactory images were obtained transabdominally in 402/478 (84.1%) and transvaginally in a further 13 patients. Cardiac defects were confidently identified in 60 fetuses and abnormalities of uncertain significance (isolated ventricular or great artery disproportion, or tricuspid regurgitation) were observed in a further 49. Defects were suspected in an additional 20 fetuses, and 286 were passed as normal. The karyotype was subsequently demonstrated to be abnormal in 70/286 (24.5%) fetuses with normal echocardiograms, and in 94/129 (72.9%) with abnormal or suspicious cardiac findings. Validation of the scan findings was possible in 241 fetuses. Normal heart structure was confirmed in 204 fetuses, and previously unsuspected cardiac abnormalities revealed in nine. Heart defects were verified in 28 fetuses, but five of these had important additional findings. There were false positive findings in three fetuses. CONCLUSIONS: Fetal echocardiography is feasible prior to 14 weeks' gestation. Cardiac defects, when present, may be identified or suspected in the majority of cases. In the risk group studied, heart defects were frequently a manifestation of chromosomal abnormality.

Chromosome Aberrations↗
PubMed2002

Blackfan-Diamond anemia and dyserythropoietic anemia presenting with increased nuchal translucency at 12 weeks of gestation.

Blackfan-Diamond anemia is a congenital hypoplastic anemia with a birth prevalence of about 1 in 200,000, usually presenting in the first few months of life and commonly associated with cardiac, urogenital and digital anomalies. Congenital dyserythropoietic anemias are a group of rare congenital anemias characterized by ineffective erythropoiesis. We report on two cases of congenital fetal anemia, one with Blackfan-Diamond anemia and one with dyserythropoietic anemia, presenting with increased nuchal translucency at 12 weeks of gestation.

Adult↗
PubMed2002

Hypophosphatasia associated with increased nuchal translucency: a report of two affected pregnancies.

Perinatal hypophosphatasia is a lethal autosomal recessive skeletal abnormality with a birth prevalence of about 1 per 100 000. It is characterized by deficiency of the tissue-nonspecific isoenzyme of alkaline phosphatase causing abnormal bone mineralization. In the two affected fetuses from the same family ultrasound examination at 14 and 12 weeks, respectively, demonstrated increased nuchal translucency thickness, hypomineralization of the skull and spine, narrowing of the chest and shortening of the limbs.

Adult↗
PubMed2002

One-stop clinic for assessment of risk for trisomy 21 at 11-14 weeks: a prospective study of 15 030 pregnancies.

OBJECTIVE: To evaluate the performance of a one-stop clinic for assessment of risk (OSCAR) for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation. METHOD: Screening for trisomy 21 was carried out by OSCAR in 15 030 singleton pregnancies with live fetuses at 11-14 weeks. The estimated risk for trisomy 21 was calculated, and the women were counseled regarding this risk and the option of invasive testing or expectant management. Follow-up of the outcome of all pregnancies was carried out. The detection and false-positive rates for different risk cut-offs were calculated. RESULTS: Fetal NT and maternal serum free beta-hCG and PAPP-A were successfully measured in all cases. Pregnancy outcome, including karyotype results or the birth of a phenotypically normal baby, was obtained from 14 383 cases. The median maternal age of these cases was 34 (range 15-49) years and in 6768 (47.1%) the age was 35 years or greater. The median gestation at screening was 12 (range 11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A was 1 in 300 or greater in 6.8% (967 of 14 240) normal pregnancies, in 91.5% (75 of 82) of those with trisomy 21 and in 88.5% (54 of 61) of those with other chromosomal defects. For a fixed false-positive rate of 5% the respective detection rates of screening for trisomy 21 by maternal age alone, maternal age and serum free beta-hCG and PAPP-A, maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry were 30.5%, 59.8%, 79.3% and 90.2%, respectively. CONCLUSION: Screening for trisomy 21 by a combination of maternal age, fetal NT and maternal serum biochemistry at 11-14 weeks can be provided in an OSCAR setting and is associated with a detection rate of about 90% for a false-positive rate of 5%.

Adult↗
PubMed2002

Screening for pre-eclampsia and fetal growth restriction in twin pregnancies at 23 weeks of gestation by transvaginal uterine artery Doppler.

OBJECTIVE: To assess the value of transvaginal uterine artery Doppler at 23 weeks of gestation in predicting the development of adverse perinatal outcomes in twin pregnancies. PATIENTS AND METHODS: Women with twin pregnancies attending for routine ultrasound examination at 23 weeks in any one of seven hospitals underwent Doppler assessment of the uterine arteries. The right and left uterine arteries were identified using color flow mapping and velocity waveforms were obtained using pulsed Doppler. The mean pulsatility index (PI) of the two arteries was determined and the presence of uterine artery notching noted. Results were compared between monochorionic and dichorionic twins, and with our previously reported data from singleton pregnancies. Screening characteristics in the prediction of pre-eclampsia, fetal growth restriction (FGR), placental abruption, fetal death and early preterm delivery were calculated. RESULTS: Uterine artery Doppler at 22-24 weeks of gestation was performed in 360 twin pregnancies, including 324 dichorionic and 36 monochorionic diamniotic twins. Complete outcome data were available in 351 (97.5%). The mean uterine artery PI did not change significantly with gestation and there was no significant difference in mean PI between the dichorionic and monochorionic groups. However, the mean PI was significantly lower in twin pregnancies than in singletons. The pregnancy was complicated by pre-eclampsia in 6.0% of cases, FGR below the 5th centile of both twins in 8.8%, abruption in 0.9%, intrauterine fetal death in 1.7% and early preterm delivery at less than 32 completed weeks of gestation in 5.7% of cases. The respective sensitivities of uterine artery mean PI above the 95th centile for these complications were 33.3%, 9.7%, 66.6%, 33.3% and 18.6%. CONCLUSIONS: In twin pregnancies PI in the uterine arteries is lower than that in singleton pregnancies, but there is no significant difference between dichorionic and monochorionic twins. Doppler assessment of the uterine arteries at 23 weeks identifies a large proportion of twin pregnancies destined to develop adverse outcomes related to uteroplacental insufficiency.

Adolescent↗
PubMed2002

Trichorionic triplet pregnancies at 10-14 weeks: outcome after embryo reduction compared to expectant management.

OBJECTIVE: To compare the outcome of trichorionic triplet pregnancies managed expectantly with those reduced to twins or singletons. METHODS: This was a retrospective study of trichorionic triplet pregnancies with three live fetuses at 10-14 (median 12) weeks' gestation referred to our unit for consideration of embryo reduction. Women were counselled as to the available options of either expectant management or embryo reduction. In those choosing reduction, a needle was inserted into the uterus transabdominally and potassium chloride was injected into the fetal heart. Using data derived from this study and from a review of studies reporting on survival and handicap by gestational age in singletons, the effects of embryo reduction on survival and handicap rates were estimated. Main outcome measures were miscarriage before 24 weeks of gestation, preterm delivery before 32 weeks, perinatal death and handicap rates. RESULTS: In total, there were 280 trichorionic triplet pregnancies and 125 of these were managed expectantly, 133 were reduced to two fetuses and 22 were reduced to one fetus. The rates of miscarriage were 3.2% for those managed expectantly, 8.3% for those reduced to twins and 13.6% for those reduced to singletons. The rates of early preterm delivery in those pregnancies that did not miscarry were 23.1%, 9.8% and 5.3%, respectively. The percentages for pregnancies with at least one survivor were 95.2%, 91.0% and 81.8%, respectively, and the median gestation at delivery was 34 weeks for the non-reduced, 36 weeks for those reduced to twins and 38 weeks for those reduced to singletons. From the published series on early preterm delivery, it was estimated that survival increases from about 27% at 24 weeks to about 98% at 32 weeks, and handicap decreases from 28% at 24 weeks to less than 5% at 32 weeks. From these estimates and the data on triplet pregnancies, it was calculated that, in triplets reduced to twins, compared to those managed expectantly, the chance of survival is similar (90.3% compared to 93.3%), but the risk of handicap may be lower (0.6% compared to 1.5% per fetus). CONCLUSIONS: In trichorionic triplet pregnancies, embryo reduction to twins does not improve the chance of survival but may reduce the rate of handicap. Reduction from triplets to singletons may reduce both the survival rate and the handicap rate among survivors.

Adult↗
PubMed2002

Fetal nasal bone length in chromosomally normal and abnormal fetuses at 11-14 weeks of gestation.

OBJECTIVE: To determine the value of measuring fetal nasal bone length at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: The fetal profile was examined and the nasal bone length was measured in 1092 fetuses immediately before chorionic villous sampling for karyotyping at 11-14 weeks of gestation. RESULTS: The median gestation was 12 (11-14) weeks. The fetal profile was successfully examined in all cases. The fetal karyotype was normal in 955 pregnancies and abnormal in 137, including 79 cases of trisomy 21. In the chromosomally normal group, the fetal nasal bone length increased significantly with crown-rump length (CRL) from a mean of 1.3 mm at a CRL of 45 mm to 2.1 mm at a CRL of 84 mm. In 54 of the 79 (68.4%) cases of trisomy 21, the nasal bone was absent. In the 25 cases with present nasal bone, the nasal bone length for the CRL was not significantly different from normal. Similarly, there were no significant differences from normal in the nasal bone length of fetuses with other chromosomal defects. CONCLUSIONS: At 11-14 weeks of gestation, the nasal bone length of chromosomally abnormal fetuses is not significantly different from normal.

Adolescent↗
PubMed2002

One-stop clinic for assessment of risk of chromosomal defects at 12 weeks of gestation.

Prenatal diagnosis of trisomy 21 requires an invasive test in women considered to be at high risk after screening. At present, there are four screening tests. For a 5% false-positive rate, the sensitivities are approximately 30% for maternal age alone, 60-70% for maternal age and second-trimester maternal serum biochemical testing, 75% for maternal age and first-trimester fetal nuchal translucency (NT) scanning, and 90% for maternal age with fetal NT and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks. This article examines the methodology of first-trimester screening and summarizes the results from all studies reporting on the implementation of this method.

Adult↗
PubMed2002

Second-trimester uterine artery Doppler screening in unselected populations: a review.

OBJECTIVE: Doppler ultrasound provides a non-invasive method for the study of the uteroplacental circulation. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, which may be the consequence of trophoblastic invasion of the spiral arteries and their conversion into low-resistance vessels. Pre-eclampsia and fetal growth restriction are associated with failure of trophoblastic invasion of spiral arteries, and Doppler studies, in these conditions, have shown that impedance to flow in the uterine arteries is increased. A series of screening studies involving assessment of impedance to flow in the uterine arteries have examined the potential value of Doppler in identifying pregnancies at risk of the complications of impaired placentation. This review examines the findings of Doppler studies in unselected populations. METHODS: Searches of a computerized medical database were performed to identify relevant studies. Only those studies that provided sufficient data to allow calculation of the performance of the test were included in the analysis. Likelihood ratios were calculated for each study and are reported for pre-eclampsia, fetal growth restriction and perinatal death as well as for more severe forms of pre-eclampsia and fetal growth restriction. RESULTS: The literature search identified 19 relevant studies, four of which were excluded from the further analysis. The main characteristics and results of the 15 remaining studies provided discrepant results, which may be the consequence of differences in Doppler technique for sampling, the definition of abnormal flow velocity waveform, differences in the populations examined, the gestational age at which women were studied and different criteria for the diagnosis of pre-eclampsia and fetal growth restriction. Nevertheless, the studies provided evidence that increased impedance to flow in the uterine arteries is associated with increased risk for subsequent development of pre-eclampsia, fetal growth restriction and perinatal death. In addition, women with normal impedance to flow in the uterine arteries constituted a group that have a low risk of developing obstetric complications related to uteroplacental insufficiency. CONCLUSIONS: The review suggests that increased impedance to flow in the uterine arteries in pregnancies attending for routine antenatal care identifies about 40% of those who subsequently develop pre-eclampsia and about 20% of those who develop fetal growth restriction. Following a positive test, the likelihood of these complications is increased by about 6 and 3.5 times, respectively.

Female↗
PubMed2002

Intrapartum sonography to determine fetal head position.

OBJECTIVE: To investigate the accuracy of intrapartum transvaginal digital examination in defining the position of the fetal head. PATIENTS AND METHODS: In 496 singleton pregnancies in labor at term, the fetal head position was determined by routine transvaginal digital examination by the attending midwife or obstetrician. Immediately before or after the clinical examination, the fetal head position was determined using transabdominal ultrasound by an appropriately trained sonographer who was not aware of the clinical findings. The digital examination was considered to be correct if the fetal head position was within 45 degrees of the ultrasound finding. The accuracy of the digital examination was examined in relation to maternal characteristics and the progress of labor. RESULTS: The position of the fetal head was determined by ultrasound examination in all 496 cases examined. Digital examination failed to define the fetal head position in 166 (33.5%) cases and, in 330 cases where the position was determined, the findings of the digital and sonographic examinations were in agreement in only 163 (49.4%) cases. The rate of correct identification of the fetal position by digital examination increased with cervical dilatation, from 20.5% at 3-4 cm to 44.2% at 8-10 cm, and was higher if the examination was carried out by an obstetrician than a midwife (50% versus 30%) and if there was absence rather than presence of caput (33% versus 25%). CONCLUSIONS: Routine digital examination during labor fails to identify the correct fetal position in the majority of cases.

Adolescent↗
PubMed2002

Congenital lymphedema presenting with increased nuchal translucency at 13 weeks of gestation.

Congenital lymphedema is an autosomal dominant condition characterized by chronic tissue swelling caused by deficient lymphatic drainage due to hypoplastic/aplastic lymphatic vessels and usually affecting the lower limbs. The locus of the gene has been identified in the long arm of chromosome 15. We report one case of congenital lymphedema presenting with increased nuchal translucency at 13 weeks of gestation.

Adult↗