Showing papers on "Amniocentesis published in 2003"

First and Second Trimester Antenatal Screening for Down's Syndrome: The Results of the Serum, Urine and Ultrasound Screening Study (SURUSS):

Abstract: Objectives To identify the most effective, safe and cost-effective method of antenatal screening for Down's syndrome using nuchal translucency (NT), maternal serum and urine markers in the first and second trimesters of pregnancy, and maternal age in various combinations.Design A prospective study of women who booked for their antenatal care at about 8-14 weeks of gestation, with follow-up to identify pregnancies with Down's syndrome ascertained through second trimester screening or at birth.Setting Twenty-five maternity units (24 in the UK and one in Austria) offering second trimester Down's syndrome serum screening that agreed to collect observational data in the first trimester.Participants The results were based on 47,053 singleton pregnancies, including 101 pregnancies with Down's syndrome.Measurements and tests NT measurements were included if obtained between 9 and 13 weeks of pregnancy; serum and urine samples were also taken and stored. Another pair of serum and urine samples was collected in the second trimester and included if obtained between 14 and 20 weeks. Urine and serum samples from each affected pregnancy and five matched controls were tested for:Serum:alphafetoprotein (AFP)total human chorionic gonadotrophin (hCG)unconjugated oestriol (uE(3))pregnancy associated plasma protein A (PAPP-A)free beta-hCG.dimeric inhibin-A.Urine:invasive trophoblast antigen (ITA)beta-core fragmenttotal hCGfree beta-hCG.The matching criteria were gestation (using an ultrasound crown-rump length or biparietal diameter measurement), duration of storage, and centre. Screening performance of the individual markers and combinations of markers together with maternal age was assessed using standard methods. In addition pairs of first and second trimester serum samples from 600 controls were tested to secure a larger set in which screening performance could be determined using distribution parameters based on dates (time since first day of the last menstrual period).Main outcome measures The following were determined for different combinations of markers:efficacy (by assessing screening performance, focusing on the false-positive rate (FPR) for an 85% detection rate (DR))safety (focusing on the number of fetal losses due to amniocentesis (or chorionic villus sampling) in 100,000 women screened)cost-effectiveness (focusing on the cost of screening 100,000 women and the cost per Down's syndrome pregnancy diagnosed).Results Efficacy (screening performance) The false-positive rates for an 85% detection rate for the main screening tests are shown in the above table, in decreasing order of screening performance:With the serum integrated test, 10 weeks is the preferred time in pregnancy for the PAPP-A measurement. For the integrated test and the combined test, the timing of the measurement of the first trimester markers is less critical.Safety The lower false-positive rate with the integrated test compared with other tests means that at an 85% detection rate there would be nine diagnostic procedure-related unaffected fetal losses per 100,000 women screened compared with 44 using the combined test or 45 with the quadruple test.Cost-effectiveness Screening using the integrated test is less costly than might be expected because the extra screening costs tend to be offset by savings in the cost of diagnosis arising from the low false-positive rate. It was estimated that to achieve an 85% detection rate the cost to the UK NHS would be pound15,300 per Down's syndrome pregnancy detected. The corresponding cost using the second trimester quadruple test would be pound16,800 and using the first trimester combined test it would be pound19,000.Conclusions Implications for healthcare The results showed that screening performance in the first trimester of pregnancy was virtually the same as that in the second trimester, and in either it was much less effective than integrating screening measurements from both trimesters into a single test. In applying these results to screening practice several conclusions can be drawn. The following tests offer the most effective and safe method of screening:overall: the integrated testif an NT measurement is not available: the serum integrated testfor women who do not attend for antenatal care until the second trimester of pregnancy: the quadruple testfor women who choose to have a screening test in the first trimester: the combined test.At a constant detection rate, the cost-effectiveness of these four tests is broadly similar, any extra screening costs tending to be offset by fewer diagnostic costs. The evidence presented in this report does not support retaining the double test, the triple test, or NT measurements on their own (with or without maternal age) because each would lead to many more women having invasive diagnostic tests, without increasing the proportion of Down's syndrome pregnancies detected.

Screening for chromosomal defects.

Abstract: Chromosomal abnormalities are major causes of perinatal death and childhood handicap. Consequently, the detection of chromosomal disorders constitutes the most frequent indication for invasive prenatal diagnosis. However, invasive testing, by amniocentesis, chorionic villus sampling (CVS) or cordocentesis, is associated with a risk of miscarriage of about 1% and therefore these tests are carried out only in pregnancies considered to be at high-risk for chromosomal defects. The methods of screening to identify the high-risk group are maternal age, ultrasound findings at 11–14 weeks and/or in the second trimester and maternal serum biochemical testing at 11–14 weeks and/or in the second trimester.

Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study.

Abstract: Prenatal pesticide exposures may adversely affect children's health. However, exposure and health research is hampered by the lack of reliable fetal exposure data. No studies have been published that report measurements of commonly used nonpersistent pesticides in human amniotic fluid, although recent studies of pesticides in urine from pregnant women and in meconium indicate that fetuses are exposed to these chemicals. Amniotic fluid collected during amniocentesis is the only medium available to characterize direct fetal exposures early in pregnancy (approximately 18 weeks of gestation). As a first step in validating this exposure biomarker, we collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%), with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L, respectively, for positive values. The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample, with geometric mean concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive values. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.

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

Abstract: 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.

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes.

Abstract: Background. Previous studies have shown an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines [interleukin (IL)-6 and IL-8] in a Swedish population, with low incidence of preterm birth, of women with preterm prelabor rupture of membranes and their correlation to preterm birth. Methods. Amniotic fluid was retrieved transabdominally from 58 patients with preterm prelabor rupture of membranes before 34 weeks of gestation. Polymerase chain reaction (PCR) analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. IL-6 and IL-8 were analyzed with enzyme-linked immunosorbent assay (ELISA). Results. Microorganisms in amniotic fluid were detected in 13 patients (25%). Patients with bacteria detected in the amniotic fluid had significantly higher levels of IL-6 and IL-8. An amniotic fluid concentrat...

Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes.

Abstract: Objective: Neutrophil defensins (HNP 1-3), bactericidal/permeability-increasing protein (BPI) and calprotectin (MRP8/14) are antimicrobial peptides stored in leukocytes that act as effector molecules of the innate immune response. The purpose of this study was to determine whether parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of these antimicrobial peptides. Study design: Amniotic fluid was retrieved by amniocentesis from 333 patients in the following groups: group 1, mid-trimester with a subsequent normal pregnancy outcome (n = 84); group 2, preterm labor and intact membranes without MIAC who delivered at term (n = 36), or prematurely (n = 52) and preterm labor with MIAC (n = 26); group 3, preterm PROM with (n = 26) and without (n = 26) MIAC; and group 4, term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentrations of HNP 1-3, BPI...

Rapid, high throughput prenatal detection of aneuploidy using a novel quantitative method (MLPA)

Abstract: Prenatal diagnosis of syndromes caused by chromosomal abnormality is a long established part of obstetric care in developed countries. In this area, there have been recent significant advances in the identification of high risk pregnancies using sophisticated serum analyte and ultrasound screening methods.1,2 For follow up diagnostic testing, karyotyping has provided the gold standard. This technology has remained essentially unchanged over 30 years, as no new technology has yet proven superior in terms of being able to detect such a wide range of abnormalities with the necessary precision. Nevertheless, molecular tests, such as fluorescent in situ hybridisation (FISH) 3 and short tandem repeat analysis,4 are now in common practice for the diagnosis of specific abnormalities. These adjunctive tests importantly decrease turnaround times from 1–2 weeks to 1–2 days. We assessed the performance of multiplex ligation dependent probe amplification (MLPA) as an alternative method for the detection of aneuploidy, which is by far the most common prenatal chromosome abnormality. This novel technique5 detects sequence dosage differences in a semi-quantitative manner and has many potential applications in diagnostic molecular genetics and cytogenetics. For example, a recent report describes its use for detection of large genomic deletions and duplications in the BRCA1 gene.6 This technology appears to have significant advantages in that it is extremely versatile in its applications, flexible in its target loci, highly automated, suitable for high throughput testing, efficient, and cost effective. Its application for aneuploidy detection has not been reported in a clinical setting. In order to assess the precision and robustness of the test, we conducted a prospective blind trial on 492 consecutive amniocentesis samples referred to our cytogenetics laboratory. ### Study design This study was designed to blind test amniocentesis samples prospectively. The samples were collected over a 4 month period as they were referred …

Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women in preterm labor.

Abstract: Background. Previous studies indicate an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth, but there is a limited amount of data available from Europe. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines (interleukin-6 and interleukin-8) in a Swedish population of women in preterm labor and their correlation with preterm birth. Methods. Amniotic fluid was retrieved transabdominally from 61 patients in preterm labor before 34 weeks of gestation. Polymerase chain reaction analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. Interleukin-6 and interleukin-8 were analyzed with enzyme-linked immunosorbent assay. Results. Microorganisms in amniotic fluid were detected in 10 patients (16%). Patients with detected bacteria in the amniotic fluid had significantly higher levels of interleukin-6 and interleukin-8. There was also an association b...

C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis.

Abstract: Objective: The purpose of this study was to determine whether concentrations of C-reactive protein (CRP) in umbilical cord plasma at birth were elevated in neonates with sepsis, an inflammatory lesion of the umbilical cord (funisitis) or who were born to mothers with microbial invasion of the amniotic cavity. Methods: Umbilical cord plasma was collected at birth from 313 singleton preterm neonates (20-35 weeks of gestation). The results of amniotic fluid culture performed within 5 days of birth, the occurrence of congenital neonatal sepsis and the presence of funisitis were assessed. Amniocentesis was performed in 152 patients within 5 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay. Results: The median cord plasma CRP concentration was significantly higher in neonates with a positive amniotic fluid culture than in those with negative culture (median 245.9 (range 11.6-4885.5) ng/ml vs....

Congenital Cytomegalovirus Infection in Twin Pregnancies: Viral Load in the Amniotic Fluid and Pregnancy Outcome

Abstract: Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks’ gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 103 genome equivalents (GE)/mL of females AF and 1.9 × 105 GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 × 104 GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.

Matrix metalloproteinase 3 in parturition, premature rupture of the membranes, and microbial invasion of the amniotic cavity.

Abstract: Objective. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. Study design. A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value <0.05 was considered statistically significant. Results. (1) MMP-3 was detected in 99.5 % (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. Conclusions. (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.

Clinical aspects, prenatal diagnosis, and pathogenesis of trisomy 16 mosaicism.

Abstract: Introduction : Analysis of data from cases of trisomy mosaicism can provide insight for genetic counselling after prenatal diagnosis and for the elucidation of the pathogenesis of trisomy during pregnancy. Methods : Statistical analysis was carried out on data from 162 cases of pregnancies with prenatal diagnosis of trisomy 16 mosaicism. Results : The majority of cases resulted in live birth (66%) with an average gestational age of 35.7 weeks and average birth weight of −1.93 standard deviations from the population mean. Among the live births 45% had at least one malformation, the most common being VSD, ASD, and hypospadias. The level of trisomy on direct CVS (cytotrophoblast) was associated with more severe intrauterine growth restriction (IUGR) and higher risk of malformation, while the level of trisomy on cultured CVS (chorionic villous stroma) was associated only with more severe IUGR. Similarly, the presence of trisomy on amniocentesis (amniotic fluid) was associated with both IUGR and malformation, while the presence of trisomy in the amniotic mesenchyme was associated only with IUGR. Surprisingly, the degree of trisomy in placental tissues appeared to be independent of the degree of trisomy in amniotic fluid and amniotic mesenchyme. The sex of the fetus was not associated with any outcome variables, although there was an excess of females (sex ratio = 0.45) that may be explained by selection against male mosaic trisomy 16 embryos before the time of CVS (∼9-12 weeks). Conclusion : The levels of trisomy in different fetal-placental tissues are significant predictors of some measures of outcome in mosaic trisomy 16 pregnancies.

Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester

Abstract: Aim: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnancies is not established. The purpose of this study was to determine this prevalence in asymptomatic patients. Methods: This was a prospective observational study of patients at low risk for viral infection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesis was analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV). Results: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen (n = 164, 23.9%), elevated maternal...

Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme

Abstract: would have been much lower (51%, 95% CI 41–62%), the false-positive rate more than twice as high (14%), and the odds of being affected in those with a positive result less favourable (1:147) than those obtained with the quadruple test. Table 2 shows detection rates for a 5% false-positive rate for all methods, before and after adjustment for the spontaneous fetal loss of affected pregnancies after about 16 weeks of gestation. 3 The adjusted results from the screening programme were similar to the estimates from statistical modelling of data from the original study with stored serum samples 4 (30%, 58%, 68%, and 75% detection rates for a 5% false-positive rate for age alone, double, triple, and quadruple tests, respectively). The adjusted detection rates in table 2 show that the quadruple test was substantially better than the double test (70% vs 57%) and moderately better than the triple test (70% vs 62%). Statistical significance testing is inappropriate in table 2 because, in expectation, each method is better than the one above it, so the null hypothesis (that there is no difference between the methods) does not apply. The table shows that the more markers that are used, the better the predictive value of the test. The additional advantage of the quadruple test over the triple test is that, at the same 5% false-positive rate, it detected 21% of the cases missed by the triple test at a cost that involved no more than the measurement of another marker in a blood sample already collected. Uptake of amniocentesis (or sometimes chorionic villus sampling) increased with increasing risk (trend test p<0·0001). Only 216 of 501 (43%) women with risks of 1 in 250–300 had an amniocentesis, whereas 105 of 141 (74%) did so if they had risks higher than 1 in 50. Among women who tested positive and had affected pregnancies (who tended to be at very high risk) 87% had an amniocentesis (62 of 71), and of these 95% (59 of 62) had a termination of pregnancy. The influence of an anomaly scan in women with screen-positive results might have led to a lower overall uptake of amniocentesis than anticipated (60%). The uptake of serum screening could not be established because the number of women who were offered such testing was not recorded. Our results, from a routine screening service, confirm the value of early second trimester serum screening over screening using maternal age alone, in contradiction to recent opinion, 5

Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation

Abstract: Background/objective: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. Study design: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. Results: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1‐ 676 pg/ml vs. median 3.2 pg/ml, range 0.1‐ 408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4‐ 676 pg/ml vs. median 11.7 pg/ml, range 1.3‐ 82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4‐ 676 pg/ml vs. median 8.0, range 0.1‐ 656 pg/ml; p < 0.05 and term: median 11.7, range 1.3‐ 82 pg/ml vs. median 3.1, range 0.1‐ 408 pg/ml; p < 0.01, respectively). Conclusions: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation.

Replicate real-time PCR testing of DNA in maternal plasma increases the sensitivity of non-invasive fetal sex determination

Abstract: Background We determined fetal sex in pregnancies referred for invasive prenatal diagnosis procedures by analysis of DNA in maternal plasma. Methods Twelve pregnancies at risk of X-linked haemophilia and 32 pregnancies at risk of chromosomal aneuploidies at a gestational age ranging from 10 to 18 weeks recruited before chorionic villus sampling or amniocentesis were involved in the study. Male fetal DNA in maternal plasma was detected by using real-time polymerase chain reaction with the SRY gene as a marker. Results The specificity of the system reached 100% (no Y signal was detected in 17 women pregnant with a female fetus) and the sensitivity reached 100% (SRY amplification in 27 examined samples). Conclusions Amplification of free fetal DNA in maternal plasma is a valid and rapid technique for predicting fetal sex in first- and second-trimester pregnancies and could allow the restriction of invasive sampling procedures to male fetuses at risk of X-linked disorders. Copyright © 2003 John Wiley & Sons, Ltd.

Prenatal ultrasound diagnosis and management of body stalk anomaly: analysis of nine singleton and two multiple pregnancies.

Abstract: Objective To determine prenatal ultrasonographic features and management of fetuses with body stalk syndrome in singleton and multiple gestations. Methods In a retrospective chart analysis we reviewed all cases with body stalk anomaly diagnosed in our prenatal unit between 1994 and 2001. During this time period we adopted a uniform approach to the investigation of cases of body stalk anomaly, including amniocentesis or chorionic villus sampling (CVS) for fetal karyotyping. A general schematic sonographic examination was performed to search for fetal abnormalities and was followed by detailed two-dimensional and color-coded Doppler echocardiography. Nuchal translucency (NT) measurements were performed before 14 weeks of gestation. Postmortem examinations of fetuses were performed following termination by induction with prostaglandin. Results Eleven fetuses with body stalk anomaly were diagnosed, including two multiple pregnancies complicated by discordant body stalk anomaly. The typical ultrasonographic features were a major abdominal wall defect, severe kyphoscoliosis, limb abnormalities, neural tube defects, and a malformed, short umbilical cord with a single artery. None of the fetuses demonstrated craniofacial defects. All placentae that were examined showed evidence of persistence of the extra-embryonic celomic cavity. NT measurements were abnormal in all cases. Fetal karyotyping was normal in ten cases. In one case CVS showed a mosaic trisomy 2 (46,XX/47,XX,+ 2). Selective fetocide was performed in one trichorionic–triamniotic triplet pregnancy in early gestation, which was followed by normal development of the remaining healthy dichorionic–diamniotic twins. In a monochorionic–diamniotic twin pregnancy with one affected fetus ultrasound surveillance showed the normal development of the unaffected twin. Conclusions We present a large series of body stalk anomaly, including multiple gestations, with thoraco- and/or abdominoplacental attachment and without craniofacial defects. This specific phenotype may be explained by embryonic maldevelopment. The typical features of body stalk anomaly can be detected by ultrasound by the end of the first trimester, which is important for patient management. Consequently, this anomaly should be distinguished from other fetal abdominal wall defects. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Factors affecting performance of prenatal genetic testing by Israeli Jewish women.

Abstract: The number of prenatal genetic tests that are being offered to women is constantly increasing. However, there is little national data as to who is performing the tests and the reasons for doing or not doing so. This study evaluated the proportion of Jewish women in Israel who perform the various prenatal genetic tests and the factors affecting the performance of these tests. It was found that 60.9% of the women performed the triple test, 50.8% of women older than 35 years performed amniocentesis, while 63.3 and 24.3% of women performed Tay-Sachs and fragile-X carrier testing respectively. Ninety-six percent of the secular women compared to only 6.7% of the ultrareligious women performed the triple test. It was also found that94.4% of the secular women, 36.4% of the religious, and none of the ultrareligious women older than 35 years performed amniocentesis. In the stepwise regression analysis, being secular, having a higher income, fewer children, and being of Ashkenazi origin remained significant factors in determining performance of Tay-Sachs carrier testing. As regards fragile-X carrier testing, being secular, having fewer than four children, and having a higher income and a supplementary medical insurance remained significant factors. The main reason reported by the women for not performing amniocentesis or the triple test was for religious or moral grounds (53.3 and 67% respectively). The main reason given for not performing Tay-Sachs or fragile-X testing was that they were not referred for the tests (76 and 82% respectively). Consideration should be given to providing first trimester prenatal diagnosis to the ultrareligious group, including state subsidized fragile-X testing and educating the primary care givers about the importance of prenatal genetic testing. The information from the present study is vital for the planning of an equitable prenatal genetic service and provides guidelines for the implementation of such services in other countries. © 2003 Wiley-Liss, Inc.

Longitudinal observation of antenatally detected congenital lung malformations (CLM): natural history, clinical outcome and long-term follow-up.

Abstract: Objective: The objective of the study is to present longitudinal observations in antenatally detected congenital lung malformations (CLM), particularly pulmonary sequestration (PS) and cystic adenomatoid malformation (CAM). Methods: Fetuses found to have a CLM on prenatal ultrasound (US) were included in this study and followed up until delivery. In all newborns radiographs and computerized tomography (CT) studies of the thorax were performed. Surgical procedures included sequesterectomy, lobectomy, segmentectomy, and non-anatomic resection. Based on prenatal US findings, intrauterine course, postpartum chest radiographs and CT scans, as well as clinical signs and surgical findings patients were divided into six groups. Results: Over a period of 6 years, routine prenatal US revealed suggestion of CLM in a series of 35 consecutive fetuses. In six cases pregnancy was terminated or the fetuses suffered fetal demise. Another four fetuses became symptomatic in utero when sequential scanning revealed hydrops, hydrothorax, and enlargement of cysts or polyhydramnios. Three cases in this group received serial therapeutic amniocentesis and serial puncture of either the hydrothorax or intrapulmonary cysts. After postpartum treatment in the intensive care unit surgical procedures were performed uneventfully and confirmed the diagnosis of CAM, PS or hybrid type lesions. In 11 patients US findings were considered to demonstrate spontaneous resolution of the lesion, but disappearance without sequelae could be confirmed only in six infants. Five infants were shown to have persistent CLM on postpartum CT scans. These infants underwent resection of the lesion within the first year of life. In 11 fetuses CLM were continuously demonstrated during pregnancy with only slight changes in size and structure. Postpartum the infants were asymptomatic and were subjected to a systematic plan of diagnostic work-up and treatment. Surgery in these infants revealed a large number of hybrid type lesions (n ¼ 5). In three infants, the primary diagnosis of PS or CAM had to be corrected during the diagnostic and therapeutic work-up. Conclusion: CLM are diagnosed antenatally with an increasing frequency and are shown to be quite different from previously applied concepts. The expected clinical outcome is far better than thought to be possible. q 2003 Elsevier B.V. All rights reserved.

Biovar diversity of Ureaplasma urealyticum in amniotic fluid: distribution,intrauterine inflammatory response and pregnancy outcomes

Abstract: OBJECTIVE: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with "parvo biovar" and those with "T960 biovar". STUDY DESIGN: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. RESULTS: 1) The "parvo biovar" was detected in 82% (63/77) and "T960 biovar" was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for "parvo biovar" and in 50% (7/14) of cases with positive for "T960 biovar"; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. CONCLUSIONS: 1) The "parvo biovar" is more frequently isolated from amniotic fluid of preterm gestations than the "T960 biovar"; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.