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This paper summarizes a survey of the blood typing capabilities of representative American laboratories as they are: 1) currently applied to disputed paternity cases and 2) these laboratories potential for utilizing additional tests in disputed paternity cases.
Two paternity cases involving black persons are reported in which possible paternal exclusions existed if the A2B red cell phenotype represented the genotype A2B. ABH transferase assays were performed to determine if the A2B phenotypes arose from the genotype A1B or A2B. These assays confirmed that all group A members carried the A1 gene and not the A2 gene. Therefore, the alleged father was not excluded in either case. The B transferase showed increased activity in both AB individuals, possibly accounting for the observed A2B red cell phenotypes. Therefore, in the presence of a B gene, accurate assignment of A subtypes using standard serological methods may not be possible.
Blood tests in cases of disputed paternity can be extremely useful even when the mother's blood sample is not available. The mean probability of exclusion (A) of red cell surface antigen, Gm, Hp, and HLA systems was determined in this situation for North American whites and blacks by creating pairs of a man and an unrelated child. In whites, the most valuable of the systems investigated to indicate nonpaternity for false fathers were HLA, Rh, Fy, and MNSs, in that order. HLA, MNSs, and Gm were the most valuable systems in blacks. With all of the genetic systems used in this study, the combined probability of exclusion (CPE) of men falsely accused of paternity, in cases where the mother is absent, is approximately 95 percent for whites and 92 percent for blacks. Since only indirect exclusions are possible without the mother, the common test panel of HLA and red cell antigens may not always allow an adequate study. Extended testing is recommended to include additional genetic systems in order to achieve an average combined probability of exclusion of at least 95 percent.
The assignment of paternity when the alleged father has died is now possible by use of a variety of allele-specific oligonucleotides after amplification of genomic DNA by the polymerase chain reaction (PCR). Issues relating to the inheritance of estates may be decided on fact rather than allegation. PCR-based genotyping of DQ alpha haplotypes from paraffin-embedded tissue of the deceased was used to prove non-paternity in the case reported here. Because the child was female, it was also possible to confirm the exclusion by using a second polymorphic site located in the factor VIII gene on the X chromosome.
In cases of disputed parentage, it is commonly thought that the probability of paternity (P) represents the probability that the tested man is the biologic father of the child whose parentage is in doubt and that the paternity index (PI) is the likelihood ratio that enters into this probability. Using the results of HLA typing in a sample of disputed parentage cases, the distribution of P was examined within two groups: actual mother-alleged father-child trios, and simulated mother-unrelated man-child trios. These distributions were found to be roughly consistent with the usual understanding of P.
Four microsatellite loci (MAF50, MAF18, OarFCB20 and MCM527) were studied in Rasa Aragonesa sheep in order to evaluate their use in paternity testing. Several population characteristics were estimated [allele frequencies. effective allele number (Ne), polymorphism informative content (PIC) and probability of excluding wrong paternities (Pe)]. In 32 randomly chosen individuals, four alleles were detected for MAF50, with 2.55 effective alleles, 0.58 PIC and 0.35 Pe. For MAF18, five alleles were identified, with 2.99 effective alleles, 0.51 PIC and 0.32 Pe. For oarFCB20, 10 alleles were observed, with 6.06 effective alleles, 0.82 PIC and 0.68 Pe. Finally, for MCM527, six alleles were found, with 3.75 effective alleles, 0.69 PIC and 0.50 Pe. When these loci were used together with serum transferrin locus, Pe rose to 97.20 per cent. Field trials confirmed the real usefulness of these techniques.
Aggression scores were obtained for 132 preadolescent inner-city males to test the hypothesis that paternal absence may differentially influence aggressive behavior. A statistically significant, two-way race by paternal absence interaction (p less than .01) indicated that, when compared to their racial-ethnic counterparts living with both parents, father-absent Puerto Ricans were equally as aggressive, father-absent blacks were less aggressive, and father-absent whites were more aggressive. Tentative interpretations of these findings were developed with a view to the demographic realities of an American inner-city.
Until the late 20th century, withholding a fatal diagnosis functioned as a paradigm for sharing other medical information with patients. The obligation of confidentiality was emphasized and disclosure was ignored. Ethicists perceived the doctor-patient relationship as oriented to therapy, reassurance, and avoiding harm. Physicians were to provide lies and truth instrumentally only insofar as they aided therapy (Jameton, A. Information disclosure. Ethical issues. In Encyclopedia of Bioethics. Revised Ed.; Reich, T.N.T., Ed.; MacMillan: New York, 1995; Vol. 3, 1225-1232). This was the era of paternalism. Since the 1960s, opinion on the role of disclosure was changed rapidly in the United States stimulated by the patient's rights movement and the rise of bioethics. The current climate supports honest and complete disclosure of medical information. In 1972, the Board of Trustees of the American Hospital Association affirmed A Patient's Bill of Rights, which states that the patient has the right to obtain from his physician complete current information concerning his diagnosis, treatment, and prognosis in terms the patient can be reasonably expected to understand (Lee, A.L.; Jacobs, G. Workshop airs patient's rights. Hospitals 1973, 47, 39-43). Bioethicists now favor full disclosure as a means of respecting patient autonomy (Katz, J. The Silent World of Doctor and Patient; Free Press: New York, 1984). The American College of Physician Ethics Manual states that disclosure to patients is a fundamental ethical requirement (American College of Physicians. American College of Physicians Ethics Manual, 3rd Ed. Ann. Intern. Med. 1992, 117, 947-960). The era of patient autonomy ended the traditional pattern of withholding information, which was characteristic of the previous era of paternalism. The Jewish view toward full disclosure of a fatal illness to a patient and especially a patient who is terminally ill is in general a negative one because of the fear that the patient may give up hope, suffer severe mental anguish (tiruf hadaat), become despondent, and die sooner than otherwise. Shortening a patient's life is strictly forbidden because Judaism espouses the concept that God given life is sacred, even only a short period thereof. Disclosure should be couched in the context of optimism. The most positive outlook should be imparted to the patient. Disclosure must be imparted with compassion, sensitivity and hope thus giving the patient an opportunity to "set his house in order" and recite the confessional penitent prayer known as viduy.
OBJECTIVE: To investigate if there is an increased risk for recurrence of hypertensive disorder in pregnancy with a new partner and whether this is affected by maternal age and the interbirth interval through use of familial material. METHODS: Data on 614 multiparous women, with confirmed de novo hypertensive disorder in a first pregnancy, were used to assess the effect of paternity and interbirth interval on recurrence of hypertensive disorders. RESULTS: There were 121 women (19.7%) who had changed partner. Recurrent hypertension occurred in 318 women (64.5%) with the same partner and in 75 women (62%) with a new partner. The odds ratio (OR) for recurrence with the same partner was 1.115 (95% CI 0.739-1.680) and with a new partner 0.897 (95% CI 0.595-1.353). The mean interbirth interval was longer for women with recurrent hypertension (4.9 vs. 4.0 years, p = 0.0002). The OR for developing recurrent hypertensive disorder was 1.154 (95% CI 1.049-1.269) for every interval year with the same partner and 1.145 (95% CI 0.958-1.368) with a new partner after correction for maternal age. CONCLUSION: In women with a positive family history and previous hypertension in pregnancy, change of paternity does not influence the risk of recurrence. Increasing interbirth interval may account for a 15% recurrence risk for each year, independent of maternal age. There was no indication that a change of partner conferred any influence on the recurrence risk that is not explained with birth interval or age.
On the basis of the existence of incompatible phenotypes between the child and the alleged father, exclusion of paternity can be obtained even when the mother is not available for testing. Incompatible phenotypes in each genetic marker system of common erythrocyte antigens and enzymes, serum proteins, and major histocompatibility antigens are compiled. The efficiencies of each system and groups of systems in the exclusion of paternity are estimated; the cumulative chance is about 88% if all the common genetic marker systems are utilized.
BACKGROUND: It is well known that miscarriage risk increases with age. However, studies usually investigate only maternal age effects. We investigated both maternal age and paternal age effects on miscarriage risk to provide insight into this frequent reproductive failure. METHODS: The last planned pregnancies (n = 3174) that ended in a birth or miscarriage were analysed in a retrospective population-based study on women aged 25-44 years in Denmark, Germany, Italy and Spain. Maternal and paternal ages were analysed together, using a single variable 'couple age' in a multivariate logistic regression analysis, with couples composed of a woman and a man both aged 20-29 years forming the reference group. RESULTS: After adjustment for various factors (e.g. reproductive history, country), we found that the risk of miscarriage was higher if the woman was aged > or = 35 years, as has already been reported in a number of studies. However, the increase in risk was much greater for couples composed of a woman aged > or = 35 years and of a man aged > or = 40 years. Potential source of bias (especially 'reproductive compensation') are discussed. CONCLUSIONS: The risk of an adverse pregnancy outcome is highest if both partners are advanced in age.
The relation between paternal occupational lead exposure and low birth weight/prematurity was examined in a retrospective cohort study. Birth weight and gestational age (1981-1992), obtained from New York State birth certificates, were compared between lead-exposed and nonexposed workers. The exposed group (n = 4,256) consisted of births to male workers of reproductive age reported to the New York State Heavy Metals Registry. The control group (n = 2,318) consisted of the offspring of a random sample of male bus drivers, frequency matched by age and residence. There were no statistically significant differences in birth weight or gestational age between the exposed and the control groups. However, workers who had elevated blood lead levels for more than 5 years had a higher risk of fathering a child with low birth weight (risk ratio = 3.85, 95% confidence interval 1.5-9.88) or prematurity (risk ratio = 2.45, 95% confidence interval 1.03-5.84) than did controls after adjustment for paternal age, low maternal education, race, residence, gravidity, maternal spontaneous abortion history, perinatal complications, adequacy of prenatal care, and infant gender. The risks of low birth weight and prematurity increased with the duration of exposure to lead. Our results were limited by the inability to control for some potential confounders, such as pregravid underweight and maternal nutrition status.
The developmental consequences of chromosomal aberrations in embryos include spontaneous abortions, morphological defects, inborn abnormalities, and genetic/chromosomal diseases. Six germ-cell mutagens with different modes of action and spermatogenic stage sensitivities were used to investigate the relationship between the types of cytogenetic damage in zygotes with their subsequent risk of postimplantation death and of birth as a translocation carrier. Independent of the mutagen used, over 98% of paternally transmitted aberrations were chromosome type, rather than chromatid type, indicating that they were formed during the period between exposure of male germ cells and initiation of the first S phase after fertilization. There were consistent one-to-one agreements between the proportions of a) zygotes with unstable aberrations and the frequencies of dead embryos after implantation (slope = 0.87, confidence interval [CI]: 0.74, 1.16) and b) zygotes with reciprocal translocations and the frequency of translocation carriers at birth (slope = 0.74, CI: 0.48, 2.11). These findings suggest that chromosomal aberrations in zygotes are highly predictive of subsequent abnormal embryonic development and that development appears to proceed to implantation regardless of the presence of chromosomal abnormalities. Our findings support the hypothesis that, for paternally transmitted chromosomal aberrations, the fate of the embryo is already set by the end of G1 of the first cell cycle of development.
Reports in the scientific literature conflict regarding the possible effects of immunizing mothers with paternal antigens on placental and fetal size of the progeny. Several investigators noted an enhancement effect, while others were unable to demonstrate any effect or found an inhibitory influence. The principal differences among these previous experiments were in dosage and frequency of administration of antigen. A series of mice (C57BL/6J females immunized against A/J-strain male spleen cells and the reciprocal) was tested over a broad range of dosages, including repetitions of those given previously by other workers. Late-gestation conceptus weights and other measurements were negatively but highly correlated, with the loge of total paternal spleen cells used for preimmunization. However, the preimmunization effect could be nullified by treatment with medroxyprogesterone during pregnancy. Prior impregnation by males of the spleen-cell donor strain also countered the preimmunization inhibition of conceptus growth. Preimmunization dosage differences do not account for discrepancies observed by previous investigators.
Most of the blood group systems have now been applied to paternity investigations. In a complicated case, an alleged father not excluded with blood group testing, could be excluded with only chromosome heteromorphisms. Chromosome heteromorphisms are inherited from parents to offspring as simple Mendelian laws. The authors' paternity testing is presented with the help of chromosome heteromorphism analysis.
Noncytotoxic antibodies were detected in sera from 6 of 7 primigravid women during the first trimester of pregnancy. Such antibodies directed to antigens expressed on paternal B lymphocytes were detectable within the first 4-5 weeks of gestation. Antibody activity toward paternal B lymphocytes was also detected in 6 of 10 placental eluates, and in 3 of 10 predelivery and 2 of 10 postdelivery maternal serum samples. When B lymphocytes from umbilical cord blood were used as target cells, antibodies were detected in 5 of 7 placental eluates, and in 3 of 7 predelivery and 2 of 7 postdelivery serum samples. These antibodies also reacted with selected members of a normal B lymphocyte panel. The concept of an immunological enhancing mechanism in normal pregnancy is supported by these data.
OBJECTIVE: To evaluate the influence of paternal age upon spontaneous abortion. METHODS: This case-control study of 13,865 women draws on data from women's antenatal or postpartum interviews in the Jerusalem Perinatal Study, a population-based cohort derived from 92,408 births in 1964-1976. Case women (n=1,506) reported spontaneous abortion in the pregnancy preceding the interview; they were compared with women reporting live births in their previous pregnancy (n=12,359). Logistic regression was used to adjust for maternal age, maternal diabetes, maternal smoking, history of spontaneous abortions before the index pregnancy, parity at interview, and interval between the index pregnancy and the interview. RESULTS: The adjusted odds ratio for spontaneous abortion was 0.59 (95% confidence interval 0.45-0.76, P< .0001) for pregnancies conceived from fathers aged younger than 25 years compared with those from fathers aged 25-29 years. For fathers age 40 years or older the odds ratio for spontaneous abortion was 1.6 (95% confidence interval 1.2-2.0, P=.0003) when compared with the same reference group. CONCLUSION: Increasing paternal age is significantly associated with spontaneous abortion, independent of maternal age and multiple other factors.
Animal studies indicate male-mediated teratogenicity for certain carcinogens/mutagens. Nevertheless, paternal occupational determinants of malformations in humans have been sparsely investigated. Data on male employees at Swedish universities from 1970 to 1989 were linked to the Medical Birth Register. The relationship between major malformations and exposure to laboratory work and to specific laboratory agents/techniques before the third trimester were analyzed using logistic regression. For major malformations, "laboratory work in general" (n = 3237) gave an adjusted odds ratio (OR) of 1.3 (95% CI = 0.8-2.1) and carcinogenic solvent use (n = 2489) of 2.0 (95% CI = 0.8-4.9) around the time of conception. For carcinogenic solvents and neural crest malformations, OR was 4.9 (95% CI =1.5-15.8). In conclusion, the prevalence of congenital malformations was not increased in offspring of males with laboratory work in general (1970-1989). Paternal work with agents such as carcinogens could, however, be of concern.