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Biomedical subjects

K Nicolaides

Publications and source records attributed to K Nicolaides.

At least 19 recordsLinked to original sources

Targeted therapy for threatened preterm labor based on sonographic measurement of the cervical length: a randomized controlled trial.

OBJECTIVE: False positive diagnosis of preterm labor is common. As a consequence, medications including corticosteroids to promote fetal lung maturity and tocolysis are prescribed unnecessarily. We tested the hypothesis that management of threatened preterm labor based on measurement of cervical length by ultrasonography can reduce the number of women who receive inappropriate treatment. METHODS: Forty-one women with threatened preterm labor for whom a clinical decision was made to prescribe antenatal corticosteroids and tocolysis were randomized to have their cervical length measured by transvaginal ultrasound (n=21) or to receive therapy as planned (n=20). Fourteen women in the ultrasound group had a cervix longer than 15 mm and the therapy was withheld, while the other seven with a short cervix were managed in the same way as the control group. RESULTS: Three women (14%) in the ultrasound group were treated inappropriately with antenatal corticosteroids because they remained undelivered for more than a week. This compared favorably with the control group where 18 out of 20 (90%) received corticosteroids unnecessarily (relative risk (RR) 0.16; 95% confidence interval (CI), 0.05-0.39). Tocolysis was given to only seven women (33.3%) in the ultrasound group compared with 20 (100%) in the control group (RR 0.3; 95% CI, 0.15-0.54). There were no babies in either group who were born prematurely without being given a full course of antenatal corticosteroid therapy. CONCLUSION: Women with threatened preterm labor and cervical length more than 15 mm should not receive tocolysis. The issue of the safety of withholding corticosteroid therapy in this clinical scenario warrants further study.

Adrenal Cortex Hormones↗

Placental ABCA1 expression is reduced in primary antiphospholipid syndrome compared to pre-eclampsia and controls.

The ATP binding cassette transporter A1 (ABCA1) mediates cellular cholesterol and phospholipid efflux, and is implicated in phosphatidylserine translocation and apoptosis. Loss of functional ABCA1 in null mice results in severe placental malformation. This study aimed to establish the placental localisation of ABCA1 and to investigate whether ABCA1 expression is altered in placentas from pregnancies complicated by pre-eclampsia and antiphospholipid syndrome. ABCA1 mRNA and protein localisation studies were carried out using in situ hybridization and immunohistochemistry. Comparisons of gene expression were performed using real-time PCR and immunoblotting. ABCA1 mRNA and protein was localised to the apical syncytium of placental villi and endothelia of fetal blood vessels within the villi. ABCA1 mRNA expression was reduced in placentas from women with APS when compared to controls (p<0.001), and this was paralleled by reductions in ABCA1 protein expression. There were no differences in ABCA1 expression between placentas from pre-eclamptic pregnancies and controls. The localisation of ABCA1 in human placenta is consistent with a role in cholesterol and phospholipid transport. The decrease in ABCA1 protein in APS may reflect reduced cholesterol transport to the fetus affecting the formation of cell membranes and decreasing the level of substrate available for steroidogenesis.

ATP Binding Cassette Transporter 1↗

Current outcome of antenally diagnosed cystic lung disease.

BACKGROUND/PURPOSE: The natural history of parenchymal lung lesions such as congenital cystic adenomatoid malformation (CCAM) and pulmonary sequestration (PS) has been altered by the advent of antenatal ultrasonography. Initial reports were characterized by a high (about 30%) incidence of adverse features (eg, hydrops) and a poor outcome and did not accord with our recent experience. The authors have reviewed the outcome of fetuses that had been diagnosed in a large tertiary referral fetal medicine unit with the aim of delineating current experience. The term cystic lung disease was used throughout to avoid unjustifiable histologic precision. METHODS: The scans of all fetuses that had been diagnosed with cystic lung disease between January 1995 and July 2001 were reviewed. The outcome of each pregnancy was established, and, where possible, all infants underwent appropriate investigations, including thoracic computed tomography (CT) scans. RESULTS: Sixty-seven fetuses had a cystic lung abnormality diagnosed from January 1995 to July 2001. The median (range) age at diagnosis was 21 (19 to 28) weeks. The lesion was right sided in 29 (43%), left in 36 (54%), and bilateral in 2 (3%); it was characterized as dominantly macrocystic in 27 (40%), microcystic in 35 (52%), and mixed in 5 (8%). Mediastinal shift was present in 30 fetuses (45%). Severe signs of fetal distress (eg, hydrops) were present in 5 fetuses (7%). Antenatal intervention was performed in 4 fetuses (thoraco-amniotic shunts [n = 3] and percutaneous intrauterine laser therapy [n = 1]). Sixty-four (96%) of the fetuses were born alive. There was 1 termination of pregnancy and 2 intrauterine deaths (all severe microcystic lesions). Forty-two infants (63%) underwent thoracotomy and appropriate excisional surgery at a median of 7.5 months (range, 1 day to 34 months). Two infants (which included the fetus having intrauterine laser therapy) died early in the postnatal period. Both were large microcystic lesions and had antenatal features of severe fetal distress. Twelve infants were investigated in the postnatal period but did not undergo surgery. Ten infants were not appropriately investigated or were lost to follow-up. Histologic examination showed definitive diagnostic features of CCAM (n = 25) or PS (n = 6). Other lesions with hybrid features of both were also seen (n = 11). There was a degree of correlation between antenatal ultrasound features (size of cyst [P =.03], in-utero behavior [P =.06], mediastinal shift [P = 0.05]) and the need for surgery but not with the final histologic diagnosis. Surgical excision was required in 45% of lesions showing late-gestation "resolution." CONCLUSIONS: Antenatally diagnosed "cystic lung disease" has an excellent prognosis in the absence of signs of severe fetal distress. The need for surgery should be based on appropriate postnatal investigations (eg, CT scans), rather than on antenatal behavior.

Abortion, Therapeutic↗

Nasal bone length throughout gestation: normal ranges based on 3537 fetal ultrasound measurements.

OBJECTIVE: To establish normal ranges for nasal bone length measurements throughout gestation and to compare measurements in two subsets of patients of different race (African-American vs. Caucasian) to determine whether a different normal range should be used in these populations. METHOD: Normal nasal bone length reference ranges were generated using prenatal measurements by a standardized technique in 3537 fetuses. RESULTS: The nasal bone lengths were found to correlate positively with advancing gestation (R(2) = 0.77, second-order polynomial). No statistical difference was found between African-American and Caucasian subjects. CONCLUSION: These reference ranges may prove to be useful in prenatal screening and diagnosis of syndromes known to be associated with nasal hypoplasia. Different normal ranges for African-American and Caucasian women are not required.

Embryonic and Fetal Development↗

Outcome of antenatally diagnosed talipes equinovarus in an unselected obstetric population.

OBJECTIVE: To investigate the natural history and outcome of fetal talipes diagnosed by routine ultrasound scanning at 18-23 weeks' gestation. PATIENTS AND METHODS: This was a retrospective study of 103 228 pregnancies undergoing routine ultrasound scanning at 18-23 weeks' gestation. A computer search was made to identify all cases of fetal talipes and the records of these patients were examined to determine the incidence of other defects and pregnancy outcome. RESULTS: The incidence of fetal talipes following routine ultrasound examination was 0.10% (107/103 228) and was bilateral in 64 (59.8%) and unilateral in 43 (40.2%) cases. In 52 (48.6%) cases, talipes was of complex etiology, as it was associated with other defects, while, in 55 (51.4%) cases, it was classified as idiopathic. In 19% of cases, an initial diagnosis of idiopathic talipes was changed to complex, because of the subsequent development of associated features. Perinatal death and long-term neurodevelopmental or musculoskeletal problems were significantly more common when the talipes was complex rather than idiopathic (odds ratio, 150; 95% confidence interval, 34-665). Adverse outcomes were also seen more frequently with bilateral compared to unilateral talipes (odds ratio, 3.44; 95% confidence interval, 1.50-7.90). CONCLUSION: The outcome of antenatally detected talipes is mainly dependent on the presence or absence of other defects. A significant proportion of cases, thought to be idiopathic at presentation, will develop associated complex features when reassessed on subsequent scans or postnatally.

Clubfoot↗

Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study.

BACKGROUND: Prenatal diagnosis of trisomy 21 requires an invasive test in women regarded as being at high risk after screening. At present there are four screening tests, and for a 5% false-positive rate, the sensitivities are about 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 scanning, and 85% for maternal age with fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks. In this study, we examined the possible improvement in screening for trisomy 21 by examining the fetal nasal bone with ultrasound at 11-14 weeks of gestation. METHODS: We did an ultrasound examination of the fetal profile in 701 fetuses at 11-14 weeks' gestation immediately before karyotyping for a possible chromosomal abnormality detected by maternal age and fetal nuchal translucency screening. The presence or absence of a nasal bone was noted. FINDINGS: The fetal profile was successfully examined in all cases. The nasal bone was absent in 43 of 59 (73%) trisomy 21 fetuses and in three of 603 (0.5%) chromosomally normal fetuses. The likelihood ratio for trisomy 21 was 146 (95% CI 50-434) for absent nasal bone and 0.27 (0.18-0.40) for present nasal bone. In screening for trisomy 21, by a combination of maternal age and fetal nuchal translucency, we estimated that inclusion of examination of the fetal profile for the presence or absence of nasal bone could increase the sensitivity to 85% and decrease the false-positive rate to about 1%. INTERPRETATION: In screening for trisomy 21, examination of the fetal nasal bone could result in major reduction in the need for invasive testing and a substantial increase in sensitivity.

Adolescent↗

A case of body stalk anomaly at 10 weeks of gestation.

We describe a case of body stalk anomaly which was diagnosed at 10 weeks of gestation on a dating scan. The fetus was visualized within the exocelomic cavity outside an apparently intact amniotic membrane. The fetus displayed multiple anomalies characteristic of body stalk syndrome including a skull and brain defect, abdominal wall defect, kyphoscoliosis and gross deformities of the lower limbs. These findings do not support early amniotic membrane rupture as the primary event in the pathogenesis of body stalk anomaly and indicate that the exocelomic location of the fetus may actually be one of the features of this complex developmental anomaly.

Abnormalities, Multiple↗

Closed gastroschisis: Antenatal and postnatal features.

Four cases of antenatally diagnosed gastroschisis are described in whom there was significant closure of the abdominal wall defect around the prolapsed midgut. In 2 cases this resulted in near-total midgut infarction and short bowel syndrome. In a further case there was entry and exit jejunal and colonic atresia and significant midgut damage but some viability of extrabdominal bowel. In the final case, although there was complete closure of the ring around the base of the midgut, no intestinal loss had occurred. In the latter 2 cases, serial antenatal ultrasound imaging had shown development of intrabdominal bowel dilatation prompting early preterm delivery. Three of these infants currently are alive and well. The authors suggest the use of the term closed (or closing) gastroschisis to describe this phenomenon. J Pediatr Surg 36:1834-1837.

Female↗

Blood gases in pregnancy at sea level and at high altitude.

OBJECTIVE: 1. To measure blood gases and minute ventilation in healthy women with normal pregnancies, compare with non-pregnant women both at sea level and at high altitude; 2. to relate the results at altitude with duration of residence there. DESIGN: Cross-sectional study. SETTING: Antenatal clinics at sea level in Lima, Peru and at high altitude 4300m in Cerro de Pasco, Peru. POPULATION: A total of 304 normal pregnant women between 7 and 41 weeks of gestation were studied, including 112 who lived at sea level and 192 at high altitude (4300m). For comparison 38 non-pregnant women (19 at sea level and 19 at high altitude) were also studied. METHODS: Arterialised blood gases, haemoglobin, pulse oximetry and minute ventilation were measured once in each woman. MAIN OUTCOME MEASURES: PO2, PCO2, pH, haemoglobin, oxygen saturation, arterial oxygen content and minute ventilation and their relationship to gestation. RESULTS: PO2, PCO2, bicarbonate, base excess and oxygen saturation were lower in pregnancies at high altitude compared with sea level; pH, haemoglobin, arterial oxygen content and minute ventilation were higher. At high altitude oxygen saturation and haemoglobin decreased towards term resulting in a fall in arterial oxygen content at the end of pregnancy. Women whose family had lived at high altitude for at least three generations maintained their oxygenation throughout pregnancy better than women whose family had lived there for less than three generations. CONCLUSIONS: In pregnancy at high altitude maternal adaptation appeared adequate in the first trimester but declined towards term. However, maternal oxygenation was maintained in those whose family had lived longest at high altitude suggesting a beneficial adaptation to a hypoxic environment, occurring over generations.

Adult↗

Prediction of outcome by computer-assisted analysis of lung area on the chest radiograph of infants with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Pulmonary hypoplasia is a major cause of mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia is characterized by low volume lungs, and affected infants are likely to have a low lung area on their chest radiograph. The authors assessed whether, in CDH infants, computer-assisted analysis of the chest radiograph lung area gave an accurate indication of lung volume, and if a low lung area was a better predictor of poor outcome (death or oxygen dependency at 28 days) than other test results. METHODS: Comparisons were made of the radiographic lung area derived by computer-assisted analysis and lung volume, assessed by measurement of functional residual capacity (FRC) on day 1 before surgical intervention and on the first postoperative day. Compliance was measured, and the maximum and modified ventilation indices and maximum Paco2 also was noted. Twenty-five CDH infants with a median gestational age of 38 weeks were studied; 18 had FRC measurements preoperatively. RESULTS: Both preoperatively and postoperatively, the lung areas and FRCs correlated significantly (r = 0.51, P<.05; r = 0.76, P<.02, respectively). Eleven infants had a poor outcome (5 infants died without an operation); that group preoperatively differed significantly from those with a good outcome with respect to having a lower compliance (P<.02) and higher maximum ventilation index (P<.01) and maximum modified ventilation index (P<.05). Only postoperatively did infants with a poor outcome versus good outcome have a significantly lower lung area (P<.05); they also had a lower increase in lung area preoperatively to postoperatively (P<.01). Receiver operator characteristic curves were constructed; comparison of the areas under the curves showed that preoperatively, a low compliance and high ventilation index were the best predictors of poor outcome. Postoperatively, a low lung area performed as well as the ventilation indices. CONCLUSION: Computer-assisted analysis of the lung area on the chest radiograph is useful in predicting outcome in CDH infants postoperatively but not preoperatively.

Hernia, Diaphragmatic↗

Constriction band of the arm following insertion of a pleuro-amniotic shunt.

In a 23-week fetus with a large left-sided pleural effusion a double pigtail pleuro-amniotic shunt was inserted uneventfully. A healthy infant was delivered at 38 weeks' gestation. One end of the shunt was in the thoracic cavity but the other end was found wrapped around the upper arm resulting in a constriction band. There was no impairment of the vascular supply to the limb or in its motor or sensory function and by 6 months of age there was only a faint ring still apparent around the upper arm.

Amniotic Band Syndrome↗

Serum CA125 at 11-14 weeks of gestation in women with morphologically normal ovaries.

In a number of pregnant women ovarian cysts are found incidentally during the routine first trimester scan. These cysts may pose diagnostic difficulties, and the measurement of serum CA125 levels can be used to aid management. In this study we measured maternal serum CA125 levels in 188 women with uncomplicated pregnancies between 11-14 weeks of gestation. All women had morphologically normal ovaries observed on ultrasound examination. The median serum CA125 levels were 23.4 U/mL (range 2.2-166.3 U/mL, 95% reference interval 5.28-70.15) and did not change significantly with gestation. We conclude that CA125 levels are increased at 11-14 weeks of gestation and cut off values which are used to assess the nature of ovarian cysts in nonpregnant women cannot be applied to pregnant women at this gestation.

Adolescent↗