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Biomedical subjects

J A Canick

Publications and source records attributed to J A Canick.

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

Second-trimester maternal serum progesterone levels in Turner syndrome with and without hydrops and in trisomy 18.

Placental proteins, such as inhibin A and hCG and its subunits, as well as the placental steroid progesterone, are elevated in second-trimester maternal serum from cases of fetal Down syndrome. Since different cellular mechanisms are required for protein versus steroid synthesis and secretion, these data suggest that a generalized placental hypersecretory phenomenon is associated with Down syndrome. Inhibin A and hCG are also elevated in cases of Turner syndrome with hydrops, and are reduced in cases of Turner syndrome without hydrops and in trisomy 18. The objective of the present study was to determine maternal serum levels of the placental steroid progesterone in cases of Turner syndrome and trisomy 18. Twenty-one cases of trisomy 18, 10 cases of Turner syndrome without hydrops and 12 cases of Turner syndrome with hydrops were identified and each matched to five control samples. Maternal serum progesterone levels were significantly elevated in Turner syndrome with hydrops (2.11 MoM), slightly reduced in Turner syndrome without hydrops (0.90 MoM) and modestly, though significantly, reduced in trisomy 18 (0.73 MoM). These data are similar to the patterns seen for inhibin A and hCG, suggesting that the overall synthetic and/or secretory activity of the placenta is increased in Turner syndrome with hydrops and decreased in Turner syndrome without hydrops and in trisomy 18. These data may be helpful in understanding the pathophysiological basis of serum marker patterns in these aneuploidies.

Case-Control Studies↗
PubMed1999

Second-trimester maternal serum analyte levels associated with fetal trisomy 13.

The aim of this study was to determine whether pregnancies affected by fetal trisomy 13 are associated with second-trimester maternal serum analyte levels different from those typical of the unaffected population. Pregnancies with trisomy 13 were identified through cytogenetics laboratories. Those which had second-trimester maternal serum screening analyte measurements were further evaluated. Maternal serum analyte levels for each case and five matched controls were statistically analysed by matched ranked-sum analysis. 28 cases of fetal trisomy 13 were identified. The median AFP, uE3 and hCG levels were 1.35 MoM, 0.71 MoM and 0.90 MoM, respectively. Only uE3 levels were statistically different (p < 0.01) from those for the unaffected population. These data suggest that second-trimester maternal serum AFP, uE3 and hCG levels are not useful in detecting fetal trisomy 13 and protocols already existing for Down syndrome or trisomy 18 screening will not detect the majority of cases of this aneuploidy.

Adolescent↗
PubMed1998

Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down syndrome pregnancy.

OBJECTIVES: Previous data have shown that inhibin A (alpha/betaA) is increased about twofold in maternal serum samples from Down syndrome pregnancy. Our objectives were to determine whether activin A (betaA/betaA) was similarly increased in maternal serum from pregnancies affected with fetal Down syndrome, and to investigate whether increased expression of each inhibin/activin subunit occurred in placental tissue from cases of fetal Down syndrome. DESIGN AND METHODS: Maternal serum total activin A levels were measured in 20 cases of fetal Down syndrome and 100 unaffected pregnancy samples. In addition, analysis of inhibin/activin alpha and betaA subunit mRNA levels was performed in placental tissue extracts from six cases of fetal Down syndrome and six tissues with a normal karyotype. RESULTS: The median total activin A level in the Down syndrome cases was 0.82 MoM (multiples of the median); values did not differ significantly (P = 0.36, Mann-Whitney U analysis) from those in unaffected pregnancies. The inhibin alpha subunit/GAPDH mRNA ratio, but not that of betaA subunit/GAPDH mRNA, was significantly greater (P < 0.01, ANOVA) in placental tissue from Down syndrome than in control placental tissue. CONCLUSIONS: Unlike inhibin A, activin A is not significantly increased in Down syndrome relative to unaffected pregnancy. Furthermore, increased amounts of maternal serum inhibin A in Down syndrome pregnancy probably result from increased placental expression of inhibin alpha, but not betaA, subunit.

Activins↗
PubMed1998

Increased concentrations of prostate-specific antigen in maternal serum from pregnancies affected by fetal Down syndrome.

Down syndrome is one of the most common causes of mental retardation in the industrialized world. Prenatal serum screening to identify mothers at risk of carrying a fetus affected with Down syndrome is presently part of routine obstetrical care. Prostate-specific antigen (PSA) concentration was measured in stored second-trimester maternal serum samples from 19 pregnancies affected with fetal Down syndrome and in 95 samples from unaffected pregnancies, with each case matched to five controls for gestational age and duration of frozen sample storage. Concentrations of PSA in Down syndrome pregnancy were significantly higher (case median = 2.28 multiples of the median; P = 0.02) than in unaffected pregnancy. PSA concentrations were not significantly correlated with the current serum screening analytes, alpha-fetoprotein, unconjugated estriol, or human chorionic gonadotropin in either cases or controls. The increased maternal serum PSA concentrations in Down syndrome pregnancy and their relative independence from other markers suggest the possible utility of PSA as a prenatal screening marker for fetal Down syndrome.

Chorionic Gonadotropin↗
PubMed1998

Second-trimester maternal serum inhibin A levels in fetal trisomy 18 and Turner syndrome with and without hydrops.

The objective was to investigate whether cases of fetal trisomy 18 and Turner syndrome with and without hydrops were associated with alterations in the second-trimester levels of maternal serum inhibin A. Twenty-one cases of trisomy 18, 10 cases of Turner syndrome without hydrops and 12 cases of Turner syndrome with hydrops were identified. Five control samples were matched to each case for date of sample collection and completed week of gestation. Inhibin A levels were modestly, but significantly reduced in cases of trisomy 18 (median = 0.88 MoM) and Turner syndrome without hydrops (median = 0.64 MoM). In contrast, inhibin A levels were markedly increased in cases of Turner syndrome with hydrops (median = 3.91 MoM). These data for Turner syndrome are similar to those for human chorionic gonadotropin (hCG). The addition of inhibin A to multiple marker screening (alpha-fetoprotein, unconjugated oestriol and hCG) resulted in a median increase in the Down syndrome risk of 2.6-fold in cases of Turner syndrome with hydrops. The addition of inhibin A to multiple marker Down syndrome screening programmes will be likely to enhance the detection of fetal Turner syndrome with hydrops, but will not contribute substantially to the detection of fetal trisomy 18.

Blood Preservation↗
PubMed1998

Endocrine analytes in multiple-marker screening.

Prenatal serum screening is based on the observation that secretory products of the placenta and fetus are altered in maternal serum of pregnancies affected with certain birth defects. Most of these products are hormones that have been previously characterized, although the pathophysiologic basis of the altered maternal serum levels of these products that occurs in association with fetal chromosome for the most part is unknown. Prenatal serum screening is in a period of transition, with the relatively recent advance of second trimester triple-marker screening (AFP, uE3, hCG) and now the improved performance of the four-marker test that adds inhibin. A. Proposed first trimester screening and other new second trimester serum markers may dramatically change prenatal screening practices as we enter the next century.

Biomarkers↗
PubMed1997

Comparison of 12 assays for detecting hCG and related molecules in urine samples from Down syndrome pregnancies.

Urine is a new medium for Down syndrome testing. In an effort to determine the best type of human chorionic gonadotropin (hCG)-related immunoassay for urine testing, we examined 14 Down syndrome and 91 unaffected pregnancy urine samples with 12 established assays. The assays included (a) those that detect hCG beta-core fragment only; (b) those that detect beta-core fragment with less than 18 per cent free beta-subunit cross-reactivity; (c) that which equally detects free beta-subunit and beta-core fragment; and (d) those that detect hCG, free beta-subunit, or combinations thereof. The seven type a and b assays had the highest sensitivity for Down syndrome. The median MOM for Down syndrome was 5.93 (range 4.73-7.53). At a 10 per cent false-positive rate, the median observed detection rate was 93 per cent (range 79-100 per cent) and the median predicted detection rate was 85 per cent (range 69-96 per cent). The assays that did not mainly detect beta-core fragment (types c and d) had poorer screening performance. The median MOM for Down syndrome was 2.70 (range 2.16-3.63 MOM). At a 10 per cent false-positive rate, the median observed detection rate was 50 per cent (range 36-64 per cent) and the median predicted detection rate was 37 per cent (range 21-62 per cent). We infer that the assays that only detect beta-core fragment, or beta-core fragment with minor free beta-subunit cross-reactivity (types a and b), are the better urine-based tests for Down syndrome screening.

Case-Control Studies↗
PubMed1997

Levels of urinary beta-core fragment, total oestriol, and the ratio of the two in second-trimester screening for Down syndrome.

Levels of beta-core fragment and total oestriol in second-trimester maternal urine samples were measured in 32 Down syndrome pregnancies and 206 control pregnancies. Beta-core fragment and total oestriol values were corrected for the urinary creatinine level and expressed as multiples of the control medians (MOM). In addition, the ratio of the beta-core fragment level to the total oestriol level, without creatinine correction, was calculated, and expressed as MOM values. The median beta-core fragment, total oestriol, and ratio levels in Down syndrome cases were 5.42, 0.64, and 9.32 MOM, respectively. In the Down syndrome pregnancies, 66 per cent of the beta-core fragment levels were above the 95th centile of control levels, while 22 per cent of the total oestriol levels were below the fifth centile of control levels. In combination with maternal age, measurement of beta-core fragment and total oestriol levels in Down syndrome pregnancy resulted in an 80 per cent detection rate at a 5 per cent false-positive rate. Use of the ratio resulted in a univariate detection rate of 72 per cent. In combination with maternal age, the ratio resulted in a detection rate of 81 per cent at a 5 per cent false-positive rate. Based on this unmatched study, the measurement of a ratio of beta-core fragment to total oestriol levels, without the need for creatinine correction, may be useful in screening for fetal Down syndrome in second-trimester urine.

Adult↗
PubMed1997

Multiple immunoreactive inhibin proteins in serum from postmenopausal women with epithelial ovarian cancer.

Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin precursors (pro-alphaC), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-alphaC inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-alphaC) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-alphaC, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-alphaC levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin secretion, especially pro-alphaC, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women.

Aged↗
PubMed1997

Maternal serum analyte levels in pregnancies with fetal Down syndrome resulting from translocations.

OBJECTIVE: Our purpose was to determine whether pregnancies affected by fetal Down syndrome resulting from Robertsonian translocations are associated with second-trimester maternal serum analyte levels different from those resulting from fetal trisomy 21. STUDY DESIGN: Pregnancies with Down syndrome caused by Robertsonian translocations were identified through the cytogenetics laboratories at the participating institutions. Those with maternal serum screening values between 15 and 20 weeks were evaluated. RESULTS: Eleven cases of fetal Down syndrome caused by Robertsonian translocations were identified. The median alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels were 0.68, 0.67, and 2.83 multiples of the median, respectively. These analyte levels are similar to those for fetal trisomy 21. CONCLUSIONS: These data suggest that Down syndrome resulting from either Robertsonian translocations or trisomy 21 will be detected in a similar percentage of cases because the second-trimester maternal serum analyte levels are similar.

Adult↗
PubMed1997

Undetectable maternal serum unconjugated estriol levels in the second trimester: risk of perinatal complications associated with placental sulfatase deficiency.

OBJECTIVE: Our purpose was to determine the prevalence of undetectably low second-trimester maternal serum unconjugated estriol levels and the association with increased perinatal morbidity or mortality in pregnancies at risk for placental sulfatase deficiency. STUDY DESIGN: Nine centers in New England identified singleton pregnancies with undetectably low unconjugated estriol levels. Each unexplained case was matched with four controls; pregnancy outcome information was sought. RESULTS: Among 130,295 pregnancies surveyed, undetectably low unconjugated estriol levels were identified in 167 (13/10,000). Explanations included fetal death (53), overestimated gestational age (50), nonpregnancy (12), and chromosome abnormalities (5). The 41 unexplained cases were compared with 163 matched controls. Male offspring were more frequent (85%) among cases than among controls (55%). Although rates of perinatal complications were not significantly different, primary cesarean sections occurred about twice as often among cases. No perinatal deaths occurred. CONCLUSIONS: Neither severity of symptoms nor perinatal morbidity or mortality currently warrant routine interpretation of unexplained undetectably low unconjugated estriol levels as a marker for placental sulfatase deficiency.

Case-Control Studies↗
PubMed1997

Serum triple-marker screening in in vitro fertilization and naturally conceived pregnancies.

OBJECTIVE: To determine whether results of second-trimester maternal serum triple-marker screening for Down syndrome and open neural tube defects in singleton pregnancies conceived from in vitro fertilization (IVF) differ from those of pregnancies conceived spontaneously. METHODS: The screen-positive rates and triple-marker levels of patients conceiving singleton pregnancies by IVF were compared to age-adjusted standards. RESULTS: Sixty-nine singleton IVF pregnancies with maternal serum screening were identified. Twenty-one (30.4%) of the 69 IVF singleton pregnancies had a positive screen for Down syndrome compared with a 14.4% expected screen-positive rate for the maternal age distribution in our observed sample (P = .013). The screen-positive rate for open neural tube defects in the measured population was similar to anticipated values based on historic controls (5.8% in IVF patients versus 5.3% in the total population). The median levels of the triple markers were 0.95 multiples of the median (MoM) for alpha-fetoprotein (AFP), 0.90 MoM for unconjugated estriol (E3), and 1.22 MoM for hCG. CONCLUSION: The increased hCG levels as well as the slightly lower AFP and unconjugated E3 levels may contribute to the higher Down syndrome screen-positive rate in this IVF singleton population. These results may be due to the number of embryos transferred, the maternal hormonal environment of the IVF process, or other factors. Pregnancies conceived by IVF may be twice as likely to have a positive maternal serum screening test. As additional data are collected, corrected standards should be determined.

Adult↗
PubMed1997

The relationship between second-trimester amniotic fluid insulin and glucose levels and subsequent gestational diabetes.

Associations between elevated amniotic fluid glucose and insulin levels in the second trimester and the subsequent development of gestational diabetes have been reported. We conducted a case-control study to determine which analyte best predicts future maternal glucose intolerance. Thirty-nine women diagnosed with gestational diabetes (criteria of Carpenter and Coustan, Am. J. Obstet. Gynecol., 144, 768, 1982) who had undergone genetic amniocentesis for advanced maternal age were matched with euglycaemic controls. Glucose and insulin concentrations were determined by analysis of stored amniotic fluid samples. No significant difference was detected between cases and controls for amniotic fluid glucose concentrations. Amniotic fluid insulin concentrations were significantly higher in cases (mean rank 4.44, P < 0.01, using matched rank analysis of variance, where 1 is the lowest and 6 is the highest rank). After conversion to multiples of the median, 20 per cent of women with subsequent gestational diabetes were found to have amniotic fluid glucose levels at or above the 90th centile, while 35 per cent of cases had similarly elevated amniotic fluid insulin levels. We conclude that second-trimester amniotic fluid insulin is a more sensitive predictor of impending glucose intolerance than amniotic fluid glucose, although neither is sufficiently powerful to use alone as a screening test.

Adult↗
PubMed1996

The detection of non-immune hydrops through second-trimester maternal serum screening.

The objective was to investigate whether non-immune hydrops in euploid pregnancies is associated with alterations in the second-trimester levels of maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). Ten singleton cases of fetal non-immune hydrops were identified. The aetiology and timing of onset of the earliest signs of non-immune hydrops, including polyhydramnios, in relation to maternal serum screening for Down syndrome were assessed. There was no clear relationship between the aetiology of non-immune hydrops and the analyte levels, as aetiologies varied widely. AFP levels were elevated overall (median = 1.78 MOM) and uE3 levels were unremarkable (median = 0.82 MOM). hCG levels were elevated (median = 3.53 MOM) when non-immune hydrops was present at the time of screening, but were unremarkable (median = 0.82 MOM) when the non-immune hydrops presented later. It is concluded that second-trimester non-immune hydrops is associated with elevated hCG levels.

Adult↗