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Biomedical subjects

J E Haddow

Publications and source records attributed to J E Haddow.

At least 19 recordsLinked to original sources
PubMed1995

Tay-Sachs disease in persons of French-Canadian heritage in northern New England.

This study sought to determine whether persons of French-Canadian heritage in northern New England are at high risk for the lethal infantile form of Tay-Sachs disease. In order to accomplish this, death records and laboratory diagnostic records were surveyed to ascertain Tay-Sachs deaths in a cohort of 372,000 live births between 1977-1986. The proportion of the total population with French-Canadian or Jewish heritage was determined from census and birth records, and the ethnic background of Tay-Sachs cases was determined from the corresponding birth records. In 1,860 births, both parents were of Ashkenazi Jewish heritage. One of those children was diagnosed with Tay-Sachs disease. In 41,000 births, both parents were of French-Canadian heritage, and in an additional 93,000 births, one parent was of French-Canadian heritage. No cases of Tay-Sachs disease were identified in the offspring of those individuals. Approximately 14 cases (95% confidence interval 8-20) would be expected, if the gene frequency approximated that reported for individuals of Ashkenazi Jewish heritage. Based on the results of this study, routine testing for Tay-Sachs disease heterozygosity is not indicated for persons of French-Canadian heritage in northern New England. This conclusion may not necessarily be valid for persons of French-Canadian heritage residing in other states. Further studies of Tay-Sachs disease mutations and prevalence among persons of French-Canadian heritage will be important to determine possible regional variations in gene frequencies.

Child↗
PubMed1995

Risk-based prenatal screening for trisomy 18 using alpha-fetoprotein, unconjugated oestriol and human chorionic gonadotropin.

Nine centres collaborated to examine the feasibility of a screening method for trisomy 18 that was based on assigning individual risk, using a combination of maternal age and measurements of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). Second-trimester measurements of these analytes were obtained from 94 trisomy 18 pregnancies. In the 89 pregnancies without an associated open defect, the median levels for AFP, uE3, and hCG were 0.65, 0.43 and 0.36 multiples of the unaffected population median, respectively. The strongest individual predictor of risk for trisomy 18 was uE3, followed by hCG, AFP, and maternal age, in that order. Using a method of individual risk estimation that is based on the three markers and maternal age, 60 per cent of pregnancies associated with trisomy 18 would be detected at a risk cut-off level of 1:100, with a false-positive rate of about 0.2 per cent. One in nine pregnancies identified as being at increased risk for trisomy 18 would be expected to have an affected pregnancy. This risk-based screening method is more efficient than an existing method that is based on fixed analyte cut-off levels. Even though the birth prevalence of trisomy 18 is low, prenatal screening can be justified when performed in conjunction with Down syndrome screening and when a high proportion of women offered amniocentesis have an affected fetus.

Adult↗
PubMed1995

Elevated midtrimester serum methylmalonic acid levels as a risk factor for neural tube defects.

The role of folic acid in the primary prevention of neural tube defects (NTDs) is well established. However, questions related to the protective mechanism remain unanswered. To help answer these questions, we designed a case-control study to assess the role of folate- and cobalamin-related metabolites in the pathogenesis of NTDs. Concentrations of folate, cobalamin, and 14 other related metabolites were measured by gas chromatography/mass spectrometry in midtrimester serum specimens from 32 women with an NTD-affected pregnancy and from 132 control women, and in serum specimens from 46 nonpregnant women who had a history of NTD-affected pregnancy and from 43 nonpregnant control women. Log-transformed means of metabolites were compared between case and control women for both the midtrimester and nonpregnant groups. In the pregnant group, serum methylmalonic acid (MMA) concentrations were higher among case women than among control women (130 vs 105 nM). There was a strong dose-response relationship between midtrimester serum MMA level and the risk for an NTD-affected pregnancy, with the relative risk increasing 13-fold for women with MMA levels > 90th percentile. In the nonpregnant group, there was no difference in serum MMA levels between case and control women (140 vs 140 nM). Thus, the serum MMA levels of women in the midtrimester of pregnancies unaffected by NTDs were significantly lower than the levels of nonpregnant women, whereas the levels of women whose pregnancies were affected by NTDs were similar to those of nonpregnant women. The finding of elevated MMA serum concentrations among women in the midtrimester of NTD-affected pregnancies suggests that cobalamin may be involved in the etiology of NTDs. The possible role of cobalamin in relation to the protective effect of folic acid needs further evaluation.

Adult↗
PubMed1995

Effect of parity on human chorionic gonadotrophin levels and Down's syndrome screening.

OBJECTIVE: To investigate further the association between parity and human chorionic gonadotrophin (hCG) levels during the second trimester and determine whether prenatal screening for Down's syndrome might be made more efficient by adjusting for this variable. METHODS: Measurements of hCG were analysed in relation to parity from a cohort of 16,675 singleton pregnancies with viable outcomes, and from 108 singleton pregnancies affected by Down's syndrome. Cigarette smoking during pregnancy and maternal age were also analysed in relation to hCG levels. RESULTS: For both unaffected pregnancies and pregnancies with Down's syndrome the median hCG levels were 7% lower in parous than in nulliparous women. A dose-response relation was also documented for the unaffected pregnancies. When para 0, para 1, and para 2 women were studied separately, hCG levels rose steadily as age advanced. Adjusting hCG levels for parity led to a 0.1% reduction in variance of the distribution of hCG measurements in unaffected pregnancies and to a negligible increase in Down's syndrome screening efficiency. CONCLUSION: The effect of parity is not sufficiently great to warrant routine adjustment of hCG levels as part of prenatal screening for Down's syndrome.

Adult↗
PubMed1994

Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening.

BACKGROUND: As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice. METHODS: We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. RESULTS: If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower. CONCLUSIONS: Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices.

Adult↗
PubMed1994

Apolipoproteins and ischaemic heart disease: implications for screening.

Apolipoproteins and lipids are established risk factors of ischaemic heart disease (IHD) but their efficacy as screening tests is not known. We therefore examined the mortality from IHD and serum concentrations of lipids and apolipoproteins in a prospective study of 21,520 men aged 35-64 years. Serum apo B was the apolipoprotein most strongly associated with IHD risk; a decrease in apo B of 10% was associated with 22% lower risk of IHD. However, measurement of apo B alone detected only 17% of all IHD deaths at the cost of a 5% false-positive rate. Combining apo B with apo AI and apo (a) increased the detection rate to 19%. With systolic blood pressure, smoking, and family history of IHD the detection rate increased to 28%. We conclude that screening for IHD by measuring apo B alone or with apo AI and apo (a) is too poor to discriminate between recommending drug therapy or lifestyle change for some and not others. It is not advisable to screen for IHD by measuring any combination of cholesterol, apo B, apo AI, apo (a) and the other risk factors. The primary aim in prevention of ischaemic heart disease should be to lower the risk factors in the population.

Adult↗
PubMed1994

Human chorionic gonadotropin and unconjugated oestriol measurements in insulin-dependent diabetic pregnant women being screened for fetal Down syndrome.

This prospective study investigates the relationship between insulin-dependent diabetes and maternal serum levels of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). It also examines the potential impact on screening for Down syndrome. The population-based cohort included 20,321 pregnant women in Maine who underwent routine serum screening for Down syndrome in the second trimester. The cohort included 52 women with insulin-dependent diabetes. Maternal serum AFP levels are now routinely adjusted for insulin-dependent diabetes. These adjustments, therefore, were made routinely in the diabetic women, but no equivalent adjustments were made for uE3 and hCG values. The initial false-positive rate (using all three markers) among the women with diabetes was not significantly different from that in the non-diabetic population (7.7 and 5.4 per cent, respectively). Prior to adjustment for insulin-dependent diabetes, the median AFP level in the 52 women was 0.73 multiples of the median (MOM); the median levels of uE3 and hCG were 0.93 and 0.98 MOM, respectively. When the uE3 and hCG levels were adjusted, the initial false-positive rate was unchanged. Median serum levels of uE3 were significantly higher in the 33 women whose onset of diabetes was prior to 19 years of age (0.99 MOM) than in the 19 women whose onset of diabetes was at age 19 or older (0.84 MOM). This is the first population-based study to investigate the relationship between diabetes and serum levels of AFP, uE3, and hCG, and confirms earlier observations from a case-control study that found only slightly lower uE3 and hCG levels.

Adult↗
PubMed1994

Maternal serum alpha-fetoprotein screening for chromosomal abnormalities: a prospective study in women aged 35 and older.

OBJECTIVE: Our purpose was to determine the detection and false-positive rates for maternal serum alpha-fetoprotein measurement to screen for fetal Down syndrome and other chromosomal abnormalities in women > or = 35 years old. STUDY DESIGN: A total of 3896 women had serum maternal serum alpha-fetoprotein levels measured routinely before amniocentesis for the indication of advanced maternal age. RESULTS: Eighty-five percent (28/33) of fetal Down syndrome pregnancies had second-trimester risks of > or = 1:270 on the basis of a combination of maternal serum alpha-fetoprotein measurement and maternal age. Risks were also > or = 1:270 in 63% of the unaffected pregnancies. Sex chromosome aneuploidies, translocations, and other nonautosomal chromosome abnormalities in this study population were not associated with altered maternal serum alpha-fetoprotein levels; 51.9% (14/27) of these, however, were also assigned risks of > or = 1:270. CONCLUSIONS: Maternal serum alpha-fetoprotein screening is more accurate than age alone for assigning individual Down syndrome risk in pregnant women > or = 35 years old. Counseling for women in this age group should include information regarding the lower sensitivity of maternal serum alpha-fetoprotein screening for detecting fetal Down syndrome and other chromosomal abnormalities (especially sex chromosome aneuploidies) compared with offering amniocentesis to these women.

Adult↗