Ceremony Honouring Dr Mourant

J. BLANGERO, Ph.D., Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, X, USA.

I. A. SCHAFER, M.D., Division of Medical Genetics, Department of Pediatrics, Case Western Reserve University. Cleveland Metropolitan General Hospital, Cleveland. Ohio, USA.

This study examines late prenatal contact, defined as 20 weeks gestational age or more, as a factor in eligibility for mid-trimester amniocentesis among 812 women of advanced maternal age presenting for obstetric services at Cleveland Metropolitan General Hospital. Regression analysis indicates that women with three or more livebirths are more likely to be ineligible for prenatal diagnostic services, as are clinic patients when compared to private patients. Black patients are more likely to be eligible than are white patients. The continued disproportionate under-representation of minority women in prenatal diagnostic services cannot be attributed to late prenatal contact.

In the United States, as elsewhere, only a small proportion of women at increased genetic risk because of advanced maternal age currently utilize the procedures of amniocentesis and prenatal diagnosis. For example, published studies indicate that currently between 13.3 and 40 per cent of these women receive prenatal diagnostic services^1-7; furthermore, low-income and minority women are seriously under-represented among these^8-13.

One partial explanation suggested to account for relatively low utilization rates generally, and the under-representation of low-income and minority women particularly, is lateness of first presentation for obstetric services^{5, 11, 14, 15}. The purpose of this paper is to examine gestational age at first presentation and the effects it has upon eligibility for prenatal diagnostic services among women of advanced maternal age in a large county hospital in the U.S.A..

The study sample comprises 812 women of advanced maternal age (i.e., women who would be 35 years of age or more at the time of delivery) who presented for obstetric services at Cleveland Metropolitan General Hospital between 1980 and 1985. This medical facility is an ideal location for this study; there is close working relationship between Medical Genetics and Obstetrics and Gynaecology. For example, all women who require sonography and amniocentesis are referred to the latter. Similarly, all women presenting at Obstetrics who will be 35 years of age or more at the time of delivery are routinely referred for genetic counselling at the same location. In addition, as the County health facility, CMGH provides required services to all women regardless of their ability to pay. In other words, two primary confounding variables noted in the literature as possibly affecting utilization of prenatal diagnostic services, i.e. patterns of physician referral and restricted access attributable to inability to pay, are reduced in the present study.

The medical records for the 812 women presenting for obstetric services were reviewed. The following variables were extracted for each individual: age, gestational age (dated from LMP), ethnicity (white or black), patient type (private or clinic), and complete pregnancy history (including numbers of livebirths, stillbirths, abortions and premature births).

All variables were dichotomized to simplify analysis. The distributions of age at first presentation for subgroups were examined using the Kolmogoroff Smirnoff 2-sample test. In addition, the relationships between independent variables were examined using standard contingency table methods. Multi-variate analysis was performed using maximum likelihood logistic regression¹⁶.

Gestational ages at first presentation for the sample population, by ethnicity and patient type, are summarized in Table 1. Mean ages at first presentation and 95 per cent confidence intervals are represented graphically in Figure 1.

There is a substantial difference in mean gestational age at first presentation between white clinic (23.4 weeks) and white private (17.7 weeks) patients. The difference is not so great between black clinic (20.8 weeks) and black private (18.7 weeks) patients. The mean gestational age for white clinic patients is greater than that of black clinic patients, followed by black private and white private patients.

The distribution of mean gestational age at first presentation for each of these subgroups (Figure 2) show great diversity between black and white, private and clinic patients. Also, it is clear that gestational age at first presentation among each of these populations deviates significantly from a normal distribution. Consequently, standard parametric techniques cannot be employed in analysis, and instead the non-parametric Kolmogoroff-Smirnoff test was used to examine the differences in observed distributions between these populations. This method examines the shape of the distributions, especially differences in means and medians, dispersion, skewness and differences in the distribution functions¹⁷ and so determines whether or not two distributions were, in effect, drawn from the same population. The results of this test show that the distribution of gestational age at first presentation for white private patients only is significantly different from all others. The distribution of white private patients has the lowest mean, and is strongly bimodal.

Examining eligibility for mid-trimester amniocentesis among these patients as determined by gestational age at first presentation prior to twenty weeks gestational age, the mean age of mother, number of live births, premature births and abortions are summarized in Table 2. Eligible patients do not differ from the ineligible in age, number of premature births previously experienced, or the number of previous abortions (although those with one or more previous abortions are more apt to present slightly earlier for prenatal care). Neither is there a significant difference between white and black patients (Table 3). There is, however, a significant difference in previous parity and in patient type; ineligible women have had more live births, and private patients are more likely to be eligible than clinic patients.

Figure 1. Mean gestational age and 95 per cent confidence intervals at first presentation in four subgroups.

Multivariate analysis provided the relative risks for each independent variable while controlling for the effects of all other independent variables. In the present context, relative risk refers to the odds that an individual will be ineligible for mid-trimester amniocentesis. Of the several regressions fitted to the data, including a general model which included all first order interaction terms between independent variables, the most parsimonious was chosen by comparing the log likelihoods using standard ratio methods¹⁸.

All interactions between independent variables were insignificant, and there was no significant effect of mother’s age, history of abortions, or previous premature births; all these were excluded from the final analysis. The overall goodness of fit of the final model (employing the Hosmer goodness of fit test) was excellent (p=0.69).

Three variables were found to be significant in this analysis; number of previous livebirths, patient type, and ethnicity (Table 4). Women with three or more previous livebirths are twice as likely to be ineligible for prenatal diagnostic services as women with fewer than three previous livebirths, clinic patients are 1.76 times as likely as private patients, and white patients are 1.79 times as likely to be ineligible for mid-trimester amniocentesis as black patients.

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2. Volodkevich. H. and Huether. C. A. 1981 Causes of low utilization of amniocentesis by women of advanced maternal age. Soc. Biol.28: 176-186.

3. Lippman-Hand. A. and Piper. M. 1981 Prenatal diagnosis for the detection of Down Syndrome: Why are so few eligible women tested. Prenatal Diagnosis 1:249-257.

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5. Roghman. K.. Dougherty. R etal. 1983 The selective utilization of prenatal genetic diagnosis. Med. Care. 21:1111-1125.

6. Baird. P. A., Sadovnick. A. D. and McGillvray. B. C. 1985 Temporal changes in the utilization of amniocentesis for prenatal diagnosis by women of advanced maternal age. 1976-1983. Prenatal Diag. 5:19 1-198.

7. Hook. F. B. and Schreinemachers. D. 1983 Trends in utilization of prenatal cytogenetic diagnosis by New York State residents in 1979 and 1980. Am. J. Public Health 73:198-202.

8. Adams. M. M.. Finley. S., Hansen. H., Jahiel, R. and Oakley, G. 1981 Utilization of prenatal genetic diagnosis in women 35 years of age and older in the United States 1977 to 1978. Am. J. Ob. Gyn. 139:673-677.

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10. Bernhardt. B. A. and Bannerman R. M. 1982 The influence of obstetricians on the utilization of amniocentesis. Prenatal Diag. 2:115-121.

11. Marion, J. P., Kassam, G.. Fernhoff, P.. Brantley, K.. Carroll, L., Zacharias, J.,Klein, L.. Priest. J. and Elias, L. 1980 Acceptance of amniocentesis by low income patients in an urban hospital. Am. J. Ob. Gyn. 138:11-15.

12. Jahiel. R. and Hansen, H. 1980 Utilization of prenatal chromosomal diagnosis in New York City. 1969-1979: Under-representation of older women and clinic patients. Am. J. Hum. Genet. 32:ll2A.

13. Ross, J. U, Blangero, J. and Schafer, 1. A. 1990 American demography and the demand for prenatal diagnostic services: The need for public health planning.

14. Hibbard, B. M., Roberts. C. J.. Evans. K. T.. Laurence, K. M. and Hoole. G. 1980 Antenatal attendance and screening for neural tube defects. Brit. J. Ob. Gyn. 87:10-12.

15. Forster. D. P. and Davison, C. M. 1977 Medical care aspects of the prenatal diagnosis of chromosome abnormalities. Soc. Sci. Med. 11:593-598.

16. Kleinbaum, D., Kupper, L. and Morgenstern, H. 1982 Epidemiologic Research: Principles and Quantitative Methods. Lifetime Learning Pub., Belmont. CA.

17. Saehs, L. 1984 Applied Statistics: A Handbook of Techniques. Springer-Verlag, NY.

18. Kendall, M, G. and Stuart, A. 1961 The Advanced Theory of Statistics. Vol. 2: Inference and Relationship. Hafner Pub. Co., NY.

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