OBJECTIVE: Because prenatal testing of fetal RhD status by amniocentesis carries small yet finite risks to the fetus and mother, this study sought to determine whether fetal DNA in maternal serum could be used to detect fetal RhD status by polymerase chain reaction (PCR). METHODS: A retrospective analysis was made of frozen serum specimens from 20 sensitized RhD-negative pregnant women (ranging from 15.0 to 36.0 weeks' gestation) who were confirmed by serology at birth to have been carrying RhD-positive fetuses. Eleven serum specimens from RhD-negative individuals served as controls. DNA was isolated from serum and used in two PCR-based methods to detect a 99 base pair (bp) DNA fragment specific for the RhD gene and a 113 bp fragment specific for the RhCE gene as control. RESULTS: Overall, in 14 (70%) of 20 RhD-positive fetuses the 99 base pair RhD-specific PCR product was detected. There was no false positive detection among the 11 control serum specimens. CONCLUSION: The results illustrate the ability to detect fetal RhD sequences in maternal serum of sensitized women. Moreover, the findings demonstrate that fetal single-gene disorders can be detected prenatally by using DNA isolated only from maternal serum.

Blood Grouping and Crossmatching↗

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Effects of timing of conception on birth weight and preterm delivery of natural family planning users.

OBJECTIVE: Various birth defects and untoward perinatal outcomes have been claimed to be associated with pregnancies conceived by gametes aged in vivo before fertilization. Thus, these outcomes were systematically assessed in pregnancies occurring in natural family planning (NFP) users. Our international multicenter cohort study of NFP pregnancies (n = 877) is by far the largest systematic study designed to assess pregnancy outcome and is of sufficient power to allow us to address the concern of low birth weight (< 2500 g) and preterm delivery (< 37 weeks gestation). STUDY DESIGN: In addition to gathering baseline medical data, evaluation was performed at 16 weeks, 32 weeks and at term. Data were collected in a systematic cohort fashion, verified by the five collaborating international recruiting centers, and analyzed by investigators in the US. Most recruiting center principal investigators are obstetrician-gynecologists and, if not, have integral relationships with such specialists. Standard criteria could thus be applied within and among centers. In our cohort, birth weight was recorded accurately at delivery. Almost all of the deliveries occurred in hospitals; thus, data should be quite reliable. Neonatal examination for anomalies was usually conducted immediately after delivery, when birth weight was recorded. RESULTS: Analysis of risk factors for low birth weight and preterm delivery showed that this population had a low risk profile. Low birth weight infants (< 2500 g) and preterm deliveries were increased among women with a history of either prior low birth weight or preeclampsia in the index pregnancy. However, mean birth weight was unaffected by the timing of conception vis à vis ovulation or pregnancy history. Mean birth weight for the 877 singleton NFP pregnancies was 3349.6 g. The risk of preterm delivery was increased among older women who drank alcohol, but there were no significant effects of timing of conception vis à vis ovulation on preterm delivery. Results held when analysis was stratified according to whether NFP was being used for contraception or to achieve pregnancy. CONCLUSIONS: Our data do not appear to show striking differences between 877 NFP pregnancies and the general obstetric population. The timing of conception vis à vis ovulation does not exert significant effects on the birth weight or preterm delivery of resulting pregnancies, a reassuring finding for NFP users.

Birth Weight↗

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Pregnancy outcome in natural family planning users: cohort and case-control studies evaluating safety.

Conceptions involving aging gametes are of relevance to natural family planning (NFP) because women using NFP to avoid pregnancy abstain from intercourse during the fertile time of the cycle. To help verify the safety of pregnancies occurring among NFP practitioners, our group has, since 1986, conducted a large cohort study involving six experienced NFP centers. Timing of conception was determined from NFP charts, in which women recorded days on which intercourse occurred. The number of days from the most probable conception intercourse to probable day of ovulation was first determined, and used as an estimate of the time gametes remained in the genital tract before fertilization. Several studies have already been completed, cohort as well as case-control in nature.

Abortion, Spontaneous↗

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Pregnancy complications in natural family planning users.

A multicenter cohort study was designed to assess pregnancy outcome among natural family planning (NFP) users, and provide the opportunity to address complications in NFP users by planning status and by timing of conception with respect to day of ovulation. There were 877 singleton births in this sample. Complications evaluated were abnormal vaginal bleeding, urinary tract infection, vaginal infection, hypertension of pregnancy, proteinuria, glycosuria, and anemia. There was no significant difference in the mean age, number of prenatal visits or birth weight among optimally and non-optimally timed pregnancies or for planned and unplanned pregnancies. There were higher incidences of "parity 2 or more" and current smokers in the non-optimally timed pregnancies and lower incidences of prior pregnancy loss and "currently employed" in the non-optimally timed pregnancies. There was little difference in pregnancy complications with respect to pregnancy timing, with the exception of a significant increased risk of vaginal bleeding late in pregnancy among non-optimally timed conceptions (11.5%) compared to optimally timed pregnancies (5.2%, RR = 2.2, 95% CI 1.3-3.7). More differences were observed in pregnancy complication rates by planning status. Unplanned pregnancies were associated with significantly more late pregnancy bleeding, vaginal infections, proteinuria, glycosuria and medication use than planned pregnancies. Unplanned pregnancies had lower incidences of maternal anemia. Complications of pregnancy were low in this NFP population, irrespective of planned versus unplanned status. Women with planned pregnancies had even fewer complications during pregnancy than women with unplanned conceptions, suggesting that women using NFP to plan their reproduction may be at particularly low risk.

Cohort Studies↗

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Heritability and molecular genetic studies of endometriosis.

Endometriosis is a common disease defined as the growth of endometrial tissue outside the uterine cavity that often results in a vast array of gynaecological problems including dyspareunia, dysmenorrhoea, pelvic pain and infertility. Despite the increasing evidence that supports a genetic component to this common gynaecological condition, the basic aetiology and pathogenesis of endometriosis remain unknown. It is likely that endometriosis is a common polygenic/multifactorial disease caused by an interaction between multiple genes as well as the environment. Such conditions do not have a clear Mendelian pattern of inheritance. Recent molecular cytogenetic studies on endometriotic tissue and an established endometriosis-derived cell line provide novel evidence that acquired chromosome-specific alterations may be involved in endometriosis, possibly reflecting clonal expansion of chromosomally abnormal cells. Molecular DNA studies examining the role of loss of heterozygosity in endometriotic lesions has identified candidate tumour suppressor gene loci, including 5q, 6q, 9p, 11q and 22q, that may play a role in the malignant transformation of endometriotic implants to endometrioid ovarian cancers. Evidence of mutations in the tumour suppressor PTEN gene in the endometrioid subtype of epithelial ovarian cancer further suggests that somatic genetic alterations represent early events in the transformation of benign endometriotic cells. Genetic factors are also likely to influence individual susceptibility to endometriosis. There is now evidence that heritable allelic differences in drug-metabolizing enzymes play an important role in the development of endometriosis. Further studies are warranted to identify major susceptibility gene(s) and the mechanism involved in endometriosis to assist in the development of better methods for early detection, diagnosis and prevention.

Endometrial Neoplasms↗

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Gender verification of female athletes.

The International Olympic Committee (IOC) officially mandated gender verification for female athletes beginning in 1968 and continuing through 1998. The rationale was to prevent masquerading males and women with "unfair, male-like" physical advantage from competing in female-only events. Visual observation and gynecological examination had been tried on a trial basis for two years at some competitions leading up to the 1968 Olympic Games, but these invasive and demeaning processes were jettisoned in favor of laboratory-based genetic tests. Sex chromatin and more recently DNA analyses for Y-specific male material were then required of all female athletes immediately preceding IOC-sanctioned sporting events, and many other international and national competitions following the IOC model. On-site gender verification has since been found to be highly discriminatory, and the cause of emotional trauma and social stigmatization for many females with problems of intersex who have been screened out from competition. Despite compelling evidence for the lack of scientific merit for chromosome-based screening for gender, as well as its functional and ethical inconsistencies, the IOC persisted in its policy for 30 years. The coauthors of this manuscript have worked with some success to rescind this policy through educating athletes and sports governors regarding the psychological and physical nature of sexual differentiation, and the inequities of genetic sex testing. In 1990, the International Amateur Athletics Federation (IAAF) called for abandonment of required genetic screening of women athletes, and by 1992 had adopted a fairer, medically justifiable model for preventing only male "impostors" in international track and field. At the recent recommendation of the IOC Athletes Commission, the Executive Board of the IOC has finally recognized the medical and functional inconsistencies and undue costs of chromosome-based methods. In 1999, the IOC ratified the abandonment of on-site genetic screening of females at the next Olympic Games in Australia. This article reviews the history and rationales for fairness in female-only sports that have led to the rise and fall of on-site, chromosome-based gender verification at international sporting events.

Chromatin↗

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Low false-positive rate of aneuploidy detection using fetal cells isolated from maternal blood.

Explore the source record for details and available documents.

Aneuploidy↗