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Biomedical subjects

D A Luthy

Publications and source records attributed to D A Luthy.

At least 19 recordsLinked to original sources
PubMed2005

Changes in placental adipocytokine gene expression associated with gestational diabetes mellitus.

Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). In this study we examined the association between changes in expression of these genes in placental tissue and GDM risk. We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. Tissues were collected from uncomplicated pregnancies (n=28) and those complicated by GDM (n=19). Gene expression was normalized to three endogenous housekeeping genes. Relative gene expression values were reported as fold change between groups. Adiponectin gene expression was out of the sensitive range of our assay. There were increases in leptin mRNA expression in GDM cases compared with controls for maternal-side (p=0.06), and fetal-side (p=0.09) placental biopsies. No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). Finally, we noted that absence or presence of GDM was a major factor in leptin mRNA expression after adjusting for maternal age, mode of delivery, parity and smoking status. In conclusion, increases in leptin mRNA expression in term placenta, but not that of its receptors, are associated with the diagnosis of GDM. Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis.

Adult↗
PubMed2004

Leptin, soluble leptin receptor and leptin gene polymorphism in relation to preeclampsia risk.

Few investigators have simultaneously evaluated leptin, soluble leptin receptor (SLR) and leptin gene polymorphisms in preeclampsia cases and controls. We examined these three biomolecular markers in 40 preeclampsia cases and 39 controls. Plasma leptin and SLR concentrations were determined using immunoassays. Genotype for the tetranucleotide repeat (TTTC)(n), polymorphism in the 3 -flanking region of the leptin gene was determined using PCR. Alleles of the polymorphism were characterized by size distributions [short repeats (class I); and long repeats (class II)]. Logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI). Leptin concentrations were higher in our cases than in the controls (53.1 4.7 vs. 17.7+/-2.4 ng/ml, p<0.05). SLR concentrations were slightly lower in our patients than in the controls (25.7+/-1.9 vs. 29.1+/-1.1 ng/ml, p>0.05). Elevated leptin (? 14.5 ng/ml) was associated with a 3.8-fold (CI 1.0-14.4) increased risk; whereas low SLR (< 28.5 ng/ml) was associated with a 6.3-fold (CI 1.7-23.2) increased risk of preeclampsia. The I/II genotype was associated with a 3.8-fold increased risk of preeclampsia (OR=3.8; 95 % CI 0.8-18.0); and the II/II genotype was not observed among our cases (0 % vs. 33 % p<0.001). Larger studies would be needed to confirm and further clarify the relations between functional variants in the leptin gene and preeclampsia risk.

Adult↗
PubMed2004

Relationship of maternal plasma leptin and risk of pre-eclampsia: a prospective study.

OBJECTIVE: We measured maternal plasma leptin concentrations in 55 women with pre-eclampsia and 487 normotensive women to determine whether elevated leptin concentrations were associated with the occurrence of pre-eclampsia. METHODS: Maternal blood samples were collected at 13 weeks' gestation, on average. Plasma leptin concentrations were determined using immunoassay. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Leptin concentrations were 78% higher in cases than control subjects (median 34.6 vs. 19.5 ng/ml; p < 0.001). Relative to women with leptin concentrations of < 27.4 ng/ml, those with elevated leptin concentrations (> or = 27.4 ng/ml) experienced a 2.3-fold increased risk of pre-eclampsia (OR 2.3; 95% CI 1.1-4.6). We observed evidence of a strong linear component of trend in risk of pre-eclampsia with increasing maternal plasma leptin concentration. Each 10-ng/ml increase in leptin concentration was associated with a 30% increase in pre-eclampsia risk (OR 1.3; 95% CI 1.1-1.5). Overweight women with elevated leptin concentrations experienced the highest risk of pre-eclampsia (OR 6.4; 95% CI 3.1-13.2) as compared with lean women with no leptin elevations. CONCLUSION: Elevated plasma leptin concentration and maternal overweight status appear to be independently associated with an increased risk of pre-eclampsia.

Female↗
PubMed2003

Influence of pre-eclampsia on fetal growth.

OBJECTIVE: We examined the effect of pre-eclampsia on fetal growth in a cohort of pregnant women delivering singleton infants. METHODS: Analyses were restricted to 155 women with pre-eclampsia and 5570 normotensive women. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. We estimated ORs for very low birth weight (VLBW; < 1500 g), low birth weight (LBW; < 2500 g), and small for gestational age (SGA; weight < or = 10th centile by each gestational age, race, sex and parity strata) in relation to maternal pre-eclampsia status. RESULTS: After adjusting for maternal age, race, smoking, Medicaid status and gestational age, the OR for VLBW was 30.7 (95% CI 7.0-134.9). Pre-eclampsia was associated with a 3.8-fold increased risk of LBW (95% CI 1.9-7.5). Women with pre-eclampsia were 3.6 times more likely to deliver an SGA newborn as compared with normotensive women (95% CI 2.3-5.7). Advanced maternal age, African-American race, parity or smoking status did not modify the associations of pre-eclampsia with LBW and SGA. CONCLUSIONS: Our results are consistent with other reports that have documented a strong relationship between pre-eclampsia and restricted fetal growth. Further, our results expand the literature by documenting a particularly strong association between pre-eclampsia and VLBW. However, our findings regarding the relationship between pre-eclampsia and fetal growth may be confounded by unmeasured factors including maternal weight prior to pregnancy and pregnancy weight gain.

Adult↗
PubMed2003

Correlates of recreational physical activity in early pregnancy.

OBJECTIVE: Despite the well-documented benefits of a physically active lifestyle, over 25% of American adults report that they never engage in regular recreational physical activity. Little is known about the determinants of physical activity among pregnant women. We investigated the predictors of physical activity in 386 normotensive pregnant women. METHODS: Participants provided information about the type, frequency and duration of each physical activity performed during the first 20 weeks of pregnancy. We calculated odd ratios (OR) for active compared with inactive women using logistic regression models. RESULTS: Approximately 61% of women reported participating in some regular physical activity during pregnancy. Walking, swimming, gardening and jogging were the most common activities. Physical activity as an adolescent (OR 4.0) and during the year before pregnancy (OR 48.9) were the strongest predictors of physical activity in pregnancy. Active women who continued to exercise during pregnancy decreased the average intensity of their exercise and the weekly duration of exercise compared with the year before pregnancy. Nulliparas were twice as likely to engage in physical activity as compared with multiparas. Education and income were positively related with physical activity. Non-White women were 40-60% less likely to engage in physical activity as compared with White women. Smokers were also less likely to engage in physical activity. High protein intake was positively associated with physical activity, while the opposite was true for high carbohydrate intake. CONCLUSIONS: The identification of determinants of physical activity in pregnancy has important implications for developing strategies aimed at promoting a physically active lifestyle among young women.

Adult↗
PubMed2001

Isolated sonographic markers for detection of fetal Down syndrome in the second trimester of pregnancy.

OBJECTIVE: To determine whether sonographic "markers" are associated with fetal Down syndrome during the second trimester and to estimate the degree of risk of individual markers using likelihood ratios. METHODS: Second-trimester (14-20 weeks) sonographic findings in 186 fetuses with trisomy 21 were compared with a control group of 8728 consecutive control fetuses. Six markers were evaluated: nuchal thickening, hyperechoic bowel, shortened femur, shortened humerus, echogenic intracardiac focus, and renal pyelectasis. RESULTS: Major or structural abnormalities were observed in 31 fetuses with trisomy 21 (16.7%) and 53 control fetuses (0.6%) (P< .001). Some type of sonographic finding (major abnormality, minor marker, or both) was observed in 68.8% of fetuses with trisomy 21 compared with 13.6% of control fetuses (P < .001). An isolated minor or "soft" marker was the only sonographic finding in 42 (22.6%) of 186 fetuses with trisomy 21 compared with 987 (11.3%) of 8728 control fetuses (P < .001). Nuchal thickening (P < .001; likelihood ratio, 11) and hyperechoic bowel (P < .001; likelihood ratio, 6.7) showed the strongest association with trisomy 21 as isolated markers, followed by shortened humerus (likelihood ratio, 5.1), echogenic intracardiac focus (likelihood ratio, 1.8), shortened femur (likelihood ratio, 1.5), and pyelectasis (likelihood ratio, 1.5). Echogenic intracardiac focus was the single most common isolated marker in both affected fetuses (7.1%) and control fetuses (3.9%) but carried a low risk (P= .046; likelihood ratio, 1.8). CONCLUSIONS: A single soft marker is commonly encountered during the second trimester among fetuses with trisomy 21. The risk of fetal Down syndrome, reflected by likelihood ratios, was determined for 6 individual markers. This information can be combined with the a priori risk to estimate the individual patient risk for fetal Down syndrome.

Adult↗
PubMed2000

Performance of a group B streptococcal prophylaxis protocol combining high-risk treatment and low-risk screening.

OBJECTIVE: This study was undertaken to evaluate a group B streptococcal protocol in a large community hospital that combined treatment of high-risk patients with rapid screening of low-risk patients. STUDY DESIGN: In a prospective cohort study from 1994 through 1996 laboring patients in a level III community hospital were considered to be at high risk for neonatal group B streptococcal transmission if they were at <37 weeks' gestation, if they had rupture of membranes >12 hours, if they were known carriers of group B streptococci, if they had a temperature > or =100 degrees F, if the gestation was complicated by fetal growth restriction or was a multiple gestation, or if they had a previous neonate infected with group B streptococci. High-risk patients were treated intravenously with antibiotics during labor. Low-risk patients were screened for group B streptococcal antigen by means of a rapid optical immunoassay. Patients with positive screening results were treated. Neonatal morbidity and mortality were evaluated. RESULTS: Two of 9932 infants delivered had group B streptococcal sepsis diagnosed. In the 2 previous years without a protocol 9 cases of neonatal group B streptococcal sepsis had been diagnosed in 8188 deliveries (P =.0287 by Fisher exact test). The 2 cases of group B streptococcal sepsis during the protocol were as follows: 1 infant born to a high-risk mother with delay in treatment and 1 infant born to a low-risk mother with negative results of both culture and rapid screen during labor. During the previous period 7 infected infants had been born to high-risk mothers and 2 had been born to low-risk mothers. The maternal group B streptococcal carriage rate during the study was 18%. Group B streptococcal rapid optical immunoassay sensitivity was 81%. Elapsed time from screening to treatment was < or =2(1/2) hours for 93% of patients. No maternal anaphylaxis, no increase in bacterial neonatal sepsis caused by organisms other than group B streptococci, and no protocol-related group B streptococcal antibiotic resistance were noted. CONCLUSION: Successful implementation and maintenance of a protocol combining treatment of high-risk patients with rapid screening of low-risk patients during labor reduced neonatal group B streptococcal sepsis.

Adult↗
PubMed1999

Maternal second trimester serum tumor necrosis factor-alpha-soluble receptor p55 (sTNFp55) and subsequent risk of preeclampsia.

Preeclampsia is characterized by diffuse vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha), which plays a key role in the cytokine network responsible for immunoregulation, is also known to contribute to endothelial dysfunction and other metabolic disturbances noted in preeclampsia. Results from cross-sectional studies and one longitudinal study indicate that TNF-alpha (or its soluble receptor, sTNFp55) is increased in the peripheral circulation and amniotic fluid of women with preeclampsia as compared with normotensive women. Between December 1993 and August 1994, prediagnostic sTNFp55 concentrations (a marker of excessive TNF-alpha release) were measured in 35 women with preeclampsia and 222 normotensive women to determine whether elevations precede the clinical manifestation of the disorder. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Mean second trimester (15-22 weeks' gestation) serum sTNFp55 concentrations, measured by enzyme-linked immunosorbent assay, were 14.4% higher in preeclamptic women than in normotensive controls (716.6 pg/ml (standard deviation 193.6) vs. 626.4 pg/ml (standard deviation 158.0); p = 0.003). The relative risk of preeclampsia increased across successively higher quintiles of sTNFp55 (odds ratios were 1.0, 1.3, 2.1, and 3.7, with the lowest quintile used as the referent; p for trend = 0.007). After adjustment for maternal age, adiposity, and parity, the relative risk between extreme quintiles was 3.3 (95% confidence interval 0.8-13.4). These findings indicate that the level of TNF-alpha in maternal circulation is increased prior to the clinical manifestation of the disorder, and they are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia. Further work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy, and to assess whether lowering of TNF-alpha concentrations in pregnancy alters the incidence and severity of preeclampsia.

Adolescent↗
PubMed1999

Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women.

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.

Adipose Tissue↗
PubMed1999

Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia.

OBJECTIVE: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)ine are higher in preeclamptics, as compared with normotensive pregnant women. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. STUDY DESIGN: We used a prospective nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia (pregnancy-induced hypertension with proteinuria) compared with 56 women who remained normotensive throughout pregnancy. Study subjects were selected from a base population of 3, 042 women who provided blood samples at an average gestational age of 16 weeks and later delivered at our center. Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Approximately 29% of preeclamptics, as compared to 13% of controls had homocyst(e)ine levels >/=5.5 micromol/l (upper decile of distribution of control values). Adjusted for maternal age, parity, and body mass-index, a second trimester elevation of homocyst(e)ine was associated with a 3. 2-fold increased risk of preeclampsia (adjusted OR = 3.2; 95% CI 1. 1-9.2; p = 0.030). There was evidence of a interaction between maternal adiposity (as indicated by her prepregnancy body mass index) and parity with second trimester elevations in serum homocyst(e)ine. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations (95% CI 2.1-14.1; p = 0.003). Women with a higher prepregnancy body mass index (>/=21.4 kg/m(2), or upper 50th percentile) and who also had elevated homocyst(e)ine levels, as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia (95% CI 1.4-32.1; p = 0.016). CONCLUSION: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed to examine the effect of dietary and/or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted.

Adult↗
PubMed1998

Age-adjusted ultrasound risk assessment for fetal Down's syndrome during the second trimester: description of the method and analysis of 142 cases.

OBJECTIVE: To describe and test a method of individual risk assessment for fetal Down's syndrome based on maternal age and second-trimester ultrasound findings. DESIGN: A case-control study of 142 fetuses with Down's syndrome was compared with 930 control fetuses with normal karyotype. All patients underwent second-trimester ultrasound at a single institution with a standardized ultrasound protocol without knowledge of fetal karyotype. Age-adjusted ultrasound risk assessment (AAURA) for Down's syndrome was performed by multiplying the a priori risk, based on maternal age, with likelihood ratios resulting from the presence or absence of specific ultrasound findings for each patient. Individual ultrasound findings were assigned likelihood ratios (LR) as follows: structural abnormality (LR 25), nuchal thickening (LR 18.6), echogenic bowel (LR 5.5), shortened humerus (LR 2.5), shortened femur (LR 2.2), echogenic intracardiac focus (LR 2), and renal pyelectasis (LR 1.6). A normal ultrasound was assigned a LR of 0.4. RESULTS: One or more ultrasound markers were identified in 68.3% (97) of fetuses with Down's syndrome compared to 12.5% of fetuses with normal karyotype. Among fetuses with positive ultrasound, 31% of those with Down's syndrome and 80% of those with normal karyotype showed a single non-structural finding. Using AAURA and a threshold of 1: 200, 74% (105 of 142) of fetuses with Down's syndrome were identified, including 61.5% (24 of 39) from women aged less than 35 years, 67.2% (45 of 67) from women aged 35-39 years inclusively, and 100% (36 of 36) from women aged 40 years or older. AAURA of 930 fetuses with normal karyotype showed an overall false-positive rate of 14.7%, including 4% (21 of 519) from women aged less than 35 years, 12.5% (42 of 337) from women aged 35-39 years inclusively, and 100% from women aged 40 years or older. CONCLUSIONS: AAURA permits improved individual counselling regarding the risk of fetal Down's syndrome following a second-trimester sonogram. For low-risk women under age 35 years, ultrasound assessment can identify over half of the affected fetuses with Down's syndrome with an acceptable false-positive rate (4%). For women aged 35-39 years, a normal ultrasound can substantially reduce the risk of unnecessary amniocentesis (12.5% from 100%) but will also miss approximately one-third of affected fetuses. Biochemical screening of maternal serum is also suggested for this group. Based on their high a priori risk, women aged 40 years or more should consider genetic amniocentesis regardless of a normal ultrasound.

Adolescent↗
PubMed1998

Urinary gonadotropin peptide levels in preeclamptic and normotensive pregnant women. Results from a pilot case-control study.

OBJECTIVE: Elevated maternal serum human chorionic gonadotropin (hCG) is an important marker of Down syndrome. Notably, women with unexplained elevated serum hCG in the second trimester experience a 2- to 5-fold increase risk of preeclampsia. Urinary gonadotropin peptide (UGP), thought to be a metabolite of hCG that is excreted into urine, has recently been shown to be elevated in Down syndrome pregnancies. We sought to examine urinary UGP levels in preeclamptic and normotensive pregnant women. METHODS: We measured UGP levels in urine collected during the third trimester from 18 women with preeclampsia and 20 normotensive controls. UGP levels were determined using enzyme immunoassay and were corrected for dilution using urinary creatinine. Statistical significance testing was done using the Wilcoxon-Mann-Whitney Rank Sum test and Student t test statistics. RESULTS: There was a statistically significant elevation in urinary UGP levels among preeclamptic cases as compared to normotensive control subjects (p = 0.013). Mean urinary UGP levels were 80.7 and 31.3 pmol/mg creatinine for preeclampsia cases and controls, respectively. Elevations in UGP levels among women with preeclampsia as compared with normotensive control subjects persisted after adjustments for possible confounding factors. CONCLUSION: These early findings suggest that elevations in urinary UGP may be a risk marker for preeclampsia. Prospective studies should further clarify the relation between urinary UGP levels and adverse pregnancy outcomes. These results are consistent with results suggesting a role of placental hypoperfusion in the etiology of preeclampsia.

Adult↗
PubMed1998

Risk of preeclampsia in relation to elaidic acid (trans fatty acid) in maternal erythrocytes.

OBJECTIVE: Trans fatty acids, formed by the partial hydrogenation of vegetable oils, are associated with increases in plasma concentrations of cholesterol, triglyceride, lipoprotein (a), and coronary heart disease risk. Trans fatty acids may also increase platelet aggregation and alter eicosanoid biosynthesis. We studied the relation between maternal dietary intake of trans fatty acids and risk of preeclampsia. METHODS: Maternal intake of elaidic acid, one of the most abundant dietary trans fatty acids and other fatty acids were estimated using gas-liquid chromatography on erythrocytes from 22 women with preeclampsia and 40 normotensive controls. Fatty acids were expressed as the percentage of total fatty acids in erythrocytes. Logistic regression procedures were used to estimate odds ratios and 95% confidence intervals. RESULTS: Mean levels of elaidic acid were 28% higher among preeclamptics (0.43 +/- 0.12) as compared with controls (0.31 +/- 0.12; p < 0.001). After adjusting for confounding factors, women with the highest levels of elaidic acid (median = 0.47) were 7.4 times (odds ratio = 7.4; 95% confidence interval 1.4-39.7) more likely to have had their pregnancy complicated by preeclampsia as compared with those women with the lowest levels (median 0.24). Risk of preeclampsia appeared to increase with increasing levels of elaidic acid (p value for linear trend = 0.05). CONCLUSION: These cross-sectional data suggest that diets high in elaidic acid may be associated with an increased risk of preeclampsia. This hypothesis should be examined in larger longitudinal studies.

Cross-Sectional Studies↗
PubMed1997

Polyhydramnios and fetal intrauterine growth restriction: ominous combination.

The purpose of this study was to evaluate the significance of polyhydramnios combined with intrauterine growth restriction. During a 6 year period, 39 fetuses were identified by prenatal sonography as having both polyhydramnios and intrauterine growth restriction. Polyhydramnios was defined as a four-quadrant amniotic fluid index of 24 or greater (mean 30.5, range 24 to 40). Intrauterine growth restriction was defined as estimated fetal weight less than the tenth percentile (Hadlock standards). The mean birth weight was 2213 g. Major anomalies were present postnatally in 92% (36 of 39) of fetuses. Among nine fetuses without sonographically detectable anomalies prenatally, six (67%) proved to have one or more anomalies at birth. Chromosome abnormalities were present in 38% (15 cases) including 10 fetuses with trisomy 18 and one with trisomy 13. The overall mortality rate was 59%. The combination of polyhydramnios and intrauterine growth restriction is ominous. The majority of fetuses have major anomalies or chromosome abnormalities, or both, even when other sonographic abnormalities are absent. Chromosome analysis and detailed fetal evaluation should be offered when polyhydramnios and intrauterine growth restriction are identified prenatally.

Abnormalities, Multiple↗
PubMed1995

Is the 15-in situ clone protocol necessary to detect amniotic fluid mosaicism?

OBJECTIVE: Our purpose was to evaluate the 15-clone analysis for detecting amniotic fluid mosaicism by the in situ method. STUDY DESIGN: A 10-year review was performed of all amniotic fluid mosaicism cases at two institutions using the in situ method exclusively, with sequential clonal analysis to determine the first and second clone in which the abnormal cell line occurred. RESULTS: Of the 28,497 amniotic fluid samples, 73 met criteria for amniotic fluid mosaicism by in situ method (0.26%). There were 54 cases (0.19%) with potential clinical significance (23 autosome and 31 sex chromosome mosaicism); 49 of the 54 cases (89%) were detected in the first six clones, including 22 of 23 involving autosomes and 27 of 31 involving sex chromosomes. In one of the six cases detected after clone 6 (46,XX/47,XX,+21) the mosaic cell line was present in 20% of the clones analyzed and was followed by a voluntary termination of the pregnancy. In the other five cases amniotic fluid mosaicism was present in < 20% of the clones; these included one case of 46,XX/47,XX+mar (15% amniotic fluid mosaicism, voluntary termination of pregnancy), two cases of 45,X/46,XY (10% to 12% amniotic fluid mosaicism, both normal at birth), and two cases of 45,X/46,XX (8% amniotic fluid mosaicism, lost to follow-up; 12% amniotic fluid mosaicism, voluntary termination of pregnancy). By limiting the analysis to six clones, approximately 20% of analysis time could be saved per case, but one autosomal amniotic fluid mosaicism case per 10,000 samples could potentially be missed. CONCLUSION: Reducing the number of clones analyzed by in situ method could result in increased efficiency, decreased costs, and minimal loss of sensitivity.

Amniotic Fluid↗
PubMed1995

Role of prenatal ultrasonography in women with positive screen for Down syndrome on the basis of maternal serum markers.

OBJECTIVE: Our purpose was to evaluate the usefulness of prenatal ultrasonography among women with a positive screen for fetal Down syndrome on the basis of three biochemical markers--maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol. STUDY DESIGN: A total of 395 women underwent prenatal ultrasonography at a single institution after being identified as screen positive (midtrimester risk > or = 1:195) on the basis of triple-marker screening between 15 and 18 weeks. Ultrasonographic findings were compared with the biochemical markers and the eventual fetal outcome for these patients. Ultrasonographic abnormalities that were evaluated included structural defects, nuchal thickening or cystic hygroma, echogenic bowel, cerebral ventricular dilatation, pyelectasis, and shortened femur. RESULTS: Among 395 patients, 374 (94.7%) had normal karyotype by genetic amniocentesis (n = 232) or postnatal follow-up (n = 142), 18 (4.5%) proved to have Down syndrome, and three had other karyotypic abnormalities. One or more ultrasonographic abnormalities were found in nine of 18 (50%) with Down syndrome compared to 27 of 377 (7.2%) other fetuses (p < 0.001). Fetuses with abnormal ultrasonography results included three with other chromosome abnormalities and five with nonchromosomal anomalies. An abnormal ultrasonography result increased the risk of Down syndrome by 5.6-fold (25% from 4.5%) and a negative result reduced the risk by 45% (2.5% from 4.5%). The value of ultrasonography is further enhanced when all chromosome abnormalities and nonchromosomal anomalies are considered. CONCLUSION: Abnormal ultrasonographic findings increase the risk for Down syndrome, whereas normal findings are less predictive of normalcy. After correction for inaccurate menstrual dates, genetic amniocentesis should be offered in spite of a normal ultrasonography result among women with positive triple screen.

Adult↗
PubMed1995

Trisomy 13 syndrome: prenatal US findings in a review of 33 cases.

PURPOSE: To determine the type and prevalence of prenatal ultrasound (US) findings in fetuses with trisomy 13. MATERIALS AND METHODS: Prenatal US findings in 33 consecutive fetuses with trisomy 13 and in 200 karyotypically normal fetuses were reviewed and compared. RESULTS: One or more abnormalities were found in 30 fetuses (91%). Major anomalies detected by means of US included holoprosencephaly (13 [39%]) or other central nervous system anomalies (19 [58%]), facial anomalies (15 [48%]), and renal (11 [33%]) and cardiac (16 [48%]) defects. Growth retardation was also present in 16 (48%). Echogenic chordae tendineae were seen in 10 (30%), which includes seven (39%) of 18 fetuses examined before 20 menstrual weeks (compared with four [2%] of 200 fetuses in the reference group [P < .001]). Other findings not generally associated with trisomy 13 but present in this series included a large cisterna magna (six [18%]), mild cerebral ventricular dilatation (three [9%]), nuchal thickening or cystic hygroma (seven [21%]), and a hypoplastic left side of the heart (seven [21%]). CONCLUSION: Prenatal US can help detect one or more anomalies in most fetuses with trisomy 13; thus, US finding can indicate whether karyotype should be tested.

Adolescent↗