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Biomedical subjects

G J Knight

Publications and source records attributed to G J Knight.

At least 73 records · Page 4Linked to original sources

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down's syndrome in the United Kingdom from about 900 a year to about 350 a year.

Chorionic Gonadotropin↗

Second-trimester serum cotinine levels in nonsmokers in relation to birth weight.

In this study the relationship between birth weight and passive exposure to tobacco smoke is assessed for the first time by serum cotinine measurements. Among 1231 nonsmoking white women whose blood was sampled during the second trimester of pregnancy, 31.4% had serum cotinine levels between 1.0 and 9.9 ng/ml and were therefore considered to be passively exposed to tobacco smoke. The crude mean birth weight of infants of the women passively exposed to smoke was 107 gm lower than that of infants of unexposed women, and that difference remained after the application of a multivariate analysis that included the major known birth weight-associated covariates. These findings are consistent with a causal relationship between passive exposure to tobacco smoke and birth weight and suggest that the dose-response relationship may not be linear.

Adult↗

Low second trimester maternal serum unconjugated oestriol in pregnancies with Down's syndrome.

Second trimester maternal serum unconjugated oestriol levels were measured in the stored serum samples from 22 pregnancies associated with Down's syndrome and 110 unaffected control pregnancies, matched for maternal age, gestational age, duration of storage of the serum sample, smoking habits and maternal weight. The serum unconjugated oestriol level of each affected pregnancy was expressed as a multiple of the median (MoM) of its five matched controls. The unconjugated oestriol levels were significantly lower in the affected pregnancies than in the unaffected pregnancies; the median MoM was 0.79 (P less than 0.05). This association between low serum unconjugated oestriol and fetal Down's syndrome early in pregnancy raises the possibility that serum unconjugated oestriol measurement may be added to maternal age and alpha-fetoprotein measurement in the antenatal screening for Down's syndrome.

Down Syndrome↗

Maternal serum unconjugated oestriol as an antenatal screening test for Down's syndrome.

The median maternal serum unconjugated oestriol level between 13 and 27 weeks gestation in 77 pregnancies associated with Down's syndrome was lower than the median level in 385 unaffected control pregnancies matched for maternal age, gestational age, and duration of serum sample storage (P less than 0.001). The median level for the affected pregnancies was 73% of that in the controls. Low unconjugated oestriol levels can be used to detect fetal Down's syndrome; at cut-off levels selected to detect at least 35% of affected pregnancies, unconjugated serum oestriol was a better screening test than either maternal age or serum alpha-fetoprotein (AFP). The use of all three variables in combination to select women with a 1:250 or greater risk of a Down's syndrome term pregnancy would yield a 45% detection rate with a false-positive rate of 5.2%. The same detection rate using maternal age alone or using age and serum AFP in combination would yield higher false-positive rates, 15% and 9.8% respectively. The addition of unconjugated oestriol to a Down's syndrome screening programme would therefore be more efficient than the use of age and AFP alone; for a given detection rate fewer women would need an amniocentesis or, for a given percentage of women having an amniocentesis, more pregnancies with Down's syndrome would be detected.

Down Syndrome↗

Second-trimester maternal serum alpha-fetoprotein levels in pregnancies associated with gastroschisis and omphalocele.

This population-based study analyzes maternal serum alpha-fetoprotein (MSAFP) distributions for 20 cases of gastroschisis and 13 cases of omphalocele occurring in singleton pregnancies from among 72,782 second-trimester pregnancies in Maine and Rhode Island screened consecutively between January 1, 1979 and February 28, 1987. Median values (and ranges) for the two lesions were 4.1 multiples of the median (0.5-29.8) for omphalocele and 7.0 multiples of the median (3.6-13.5) for gastroschisis. The MSAFP distributions for the two conditions were both log-Gaussian, and the log standard deviation was smaller for gastroschisis than for omphalocele. The MSAFP screening sensitivity was greater for gastroschisis than for omphalocele at any given cutoff, and the overall sensitivity of this screening process for detecting open ventral wall defects will differ, therefore, depending upon the relative proportion of gastroschisis and omphalocele cases that occur in the screened population.

Female↗

Prophylaxis against gonococcal ophthalmia neonatorum. A prospective study.

The incidence of gonococcal ophthalmia neonatorum (GON) in the area served by the Peninsula Maternity and Neonatal Services in Cape Town is 273/100,000 live births. Two prophylactic agents, 1% silver nitrate ophthalmic solution and 0.5% erythromycin ophthalmic ointment, were introduced in routine eye care of the newborn in the main academic obstetric units. These agents resulted in a significant decrease in the incidence of GON to 34/100,000 live births. The alternative forms of prophylaxis against GON are discussed and the need for reinstitution of prophylaxis is emphasised.

Drug Evaluation↗

Very low versus undetectable maternal serum alpha-fetoprotein values and fetal death.

Very low maternal serum alpha-fetoprotein (MSAFP) levels (less than 10 ng/mL) are known to be associated with non-viable pregnancies, including conditions such as fetal death, molar pregnancies, and non-pregnancies. There has not been agreement, however, as to whether very low MSAFP levels indicate already existing fetal deaths or are actually predictive. We analysed 230 pregnancies with MSAFP levels less than 10 ng/mL from among 15,807 women (1.5 per cent) screened consecutively during a three-year period and identified 26 non-viable pregnancies, 22 of which were diagnosed sonographically as part of the screening process (17 missed abortions, 3 blighted ova, 2 non-pregnancies). Furthermore, 20 of these 22 pregnancies were associated with essentially undetectable MSAFP levels (less than 5 ng/mL). Our data indicate that pregnancies with MSAFP values less than 5 ng/mL are the group most strongly associated with fetal non-viability and that very low MSAFP values are not strongly predictive for fetal death.

Female↗

Determination of nicotine and cotinine in human serum and urine: an interlaboratory study.

An interlaboratory study aimed at determining nicotine and cotinine in human serum and urine was carried out. 11 laboratories from 6 countries, all experienced in performing nicotine and cotinine determinations in biological fluids by radioimmunoassay (RIA) and/or gas chromatography (GC) were involved. Each of them received 18 serum and 18 urine samples. The specimens were obtained from 8 smokers and 10 non-smokers; 2 samples from non-smokers were spiked with defined amounts of nicotine and cotinine. All the laboratories distinguished perfectly between the smokers and the non-smokers and according to cotinine levels in serum the laboratories ranked the samples with good agreement. There were systematic differences in the absolute values between the laboratories. The ratios of urinary cotinine concentrations between active and passive smokers differed widely from laboratory to laboratory. The reasons for this are not yet known and necessitate further investigation.

Chromatography, Gas↗

Cigarette consumption and serum cotinine in relation to birthweight.

The concentration of serum cotinine (the major metabolite of nicotine) was measured in sera from 4211 women at between 15 and 21 weeks gestation to determine whether a serum cotinine level was a better predictor of low birthweight than the self-reported number of cigarettes smoked per day. Both cotinine levels and smoking history were significantly associated with reduced birthweight, but cotinine correlated significantly better. Smokers of greater than or equal to 25 cigarettes per day, representing the 2.7% of women with the greatest cigarette consumption, had infants 289 g lighter than the 68% of women who were nonsmokers. Women with serum cotinine levels in the top 2.7% (greater than or equal to 284 ng/ml) had infants 441 g lighter than the 68% of women with the lowest cotinine levels (less than or equal to 24 ng/ml). Our results strengthen the evidence linking smoking with low birthweight and also demonstrate that cotinine can be satisfactorily used to assess and monitor cigarette smoking in pregnancy.

Birth Weight↗

Can low birth weight after elevated maternal serum alpha-fetoprotein be explained by maternal weight?

Low birth weight infants are delivered with increased frequency in women who have elevated maternal serum alpha-fetoprotein values in the second trimester. Maternal serum alpha-fetoprotein elevations, however, are found more often in lighter-weight women, a group known to have lower-weight infants regardless of maternal serum alpha-fetoprotein levels. To clarify the association between elevated maternal serum alpha-fetoprotein levels and low birth weight independent of maternal weight, we applied a weight correction formula to maternal serum alpha-fetoprotein values from 9507 singleton viable pregnancies without major fetal malformations. Before adjusting for weight, 486 of the women (5.1%) had maternal serum alpha-fetoprotein values of 2.0 or more multiples of the median. The weight adjustment process removed 100 lighter-weight women from this category, added 58 heavier women, and led to an equivalent proportion of women in the various weight categories who were classified as having maternal serum alpha-fetoprotein values of 2.0 or more multiples of the median. Of the 388 low birth weight pregnancies (2500 g or less), 50 initially had maternal serum alpha-fetoprotein values of 2.0 or more multiples of the median; after weight adjustment, seven lighter-weight women were removed, four heavier women were added, the median birth weight fell from 2217 to 1956 g, and a threefold increase in risk was found for low birth weight outcome regardless of weight class. Maternal serum alpha-fetoprotein elevations predict increased risk for low birth weight outcome independent of maternal weight.

Birth Weight↗

Alpha-fetoprotein, vaginal bleeding and pregnancy risk.

To assess the interrelation between maternal serum alpha-fetoprotein (MSAFP) levels and vaginal bleeding as a combined pregnancy risk factor, we studied 6829 singleton pregnancies without fetal malformations during the second trimester. The predictive powers of the two risk factors, analysed separately, are consistent with published reports in relation to fetal death and low birthweight. Until now, however, these two risk factors have not been analysed together. The present study demonstrates that MSAFP and vaginal bleeding are largely independent of each other as predictors of fetal death, relative risks being 0.7 (MSAFP less than 0.7 multiples of the median (MoM), vaginal bleeding absent), 3.5 (MSAFP less than 2.0 MoM vaginal bleeding present), 5.8 (MSAFP greater than or equal to 2.0 MoM, vaginal bleeding absent), and 12.6 (MSAFP greater than or equal to 2.0 MoM, vaginal bleeding present). Corresponding risks for low birthweight are: 0.7, 1.8, 2.5 and 1.6 (mean birthweights in the four categories are 3516 g, 3407 g, 3238 g, and 3176 g).

Female↗