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Biomedical subjects

A J Wilcox

Publications and source records attributed to A J Wilcox.

At least 19 recordsLinked to original sources
PubMed2006

Bleeding following pregnancy loss before 6 weeks' gestation.

BACKGROUND: Pregnancy loss before 6 weeks' gestation is common, but little has been reported about the associated bleeding. We compared women's bleeding following a pregnancy loss before 6 weeks' gestation with their typical menstruation. METHODS: Women provided daily urine samples while trying to become pregnant and recorded the number of pads and tampons used each day. Thirty-six women had complete bleed data for a loss before 6 weeks' gestation and one or more non-pregnant cycles. RESULTS: Mean bleed length following a pregnancy loss was 0.4 days longer than the woman's average menstrual bleed (P = 0.01), primarily because of more days of light bleeding. Although there was no overall increase in the total number of pads plus tampons used, women with losses bled less than their typical menses following pregnancies of very short duration and more than usual for the pregnancies lasting the longest. CONCLUSIONS: Overall, the bleeding associated with pregnancy loss before 6 weeks' gestation is similar to menstrual bleeding and unlikely to be recognized as pregnancy loss. The intriguing finding that pregnancies of very short duration were associated with less bleeding than the woman's typical menses might reflect endometrial factors associated with loss.

Abortion, Spontaneous↗
PubMed2004

On the frequency of intercourse around ovulation: evidence for biological influences.

BACKGROUND: Intercourse in mammals is often coordinated with ovulation, for example through fluctuations in libido or by the acceleration of ovulation with intercourse. Such coordination has not been established in humans. We explored this possibility by examining patterns of sexual intercourse in relation to ovulation. METHODS: Sixty-eight sexually active North Carolina women with either an intrauterine device or tubal ligation provided data for up to three menstrual cycles. These women collected daily urine specimens and kept daily diaries of intercourse and menstrual bleeding. Major estrogen and progesterone metabolites excreted in urine were used to identify the day of ovulation. The fertile days of the cycle were defined as the 6 consecutive days ending with ovulation. Women contributed a total of 171 ovulatory cycles. Menstrual bleeding days were excluded from analysis. RESULTS: The frequency of intercourse rose during the follicular phase, peaking at ovulation and declining abruptly thereafter. The 6 consecutive days with most frequent intercourse corresponded with the 6 fertile days of the menstrual cycle. Intercourse was 24% more frequent during the 6 fertile days than during the remaining non-bleeding days (P < 0.001). CONCLUSIONS: There apparently are biological factors that promote intercourse during a woman's 6 fertile days.

Adult↗
PubMed2003

Vaginal bleeding in very early pregnancy.

INTRODUCTION: Little is known about the occurrence and patterns of vaginal bleeding during the earliest stages of pregnancy. We explore this in a prospective study of early pregnancy. METHODS: A total of 221 healthy women kept daily diaries and provided daily urine samples while trying to become pregnant. Of these, 151 women became clinically pregnant [i.e. pregnancy that lasted >/=6 weeks beyond last menstrual period (LMP)] during the study. Diaries provided information on days with vaginal bleeding and sexual intercourse. Urine hormone assays were used to identify ovulation and implantation. Women were interviewed about their medical histories and lifestyle factors. RESULTS: A total of 14 women (9%) recorded at least 1 day of vaginal bleeding during the first 8 weeks of pregnancy. Twelve of these 14 pregnancies continued to a live birth. Bleeding tended to occur around the time when women would expect their periods, although rarely on the day of implantation. Bleeding was not associated with intercourse. CONCLUSIONS: Early bleeding in clinical pregnancies is generally light, and not likely to be mistaken for LMP. Thus, early bleeding is unlikely to contribute to errors in LMP-based gestational age. We found no support for the hypothesis that implantation can produce vaginal bleeding. Similarly, intercourse did not cause bleeding. Nearly all women with bleeding went on to have successful pregnancies.

Adult↗
PubMed2002

Reliability of serial urine HCG as a biomarker to detect early pregnancy loss.

BACKGROUND: To examine the reliability of HCG as a biomarker for early pregnancy loss, five experienced researchers independently assessed data from 153 menstrual cycles, determining whether each cycle represented 'no conception,' a 'continuing conception' or a 'conception lost.' METHODS: Urine samples were analysed by immunoradiometric assay using a combination of capture antibodies for the intact heterodimer (B109) and for an epitope common to the beta subunit and the beta core fragment (B204). For each cycle, HCG data were presented as graphs of daily assay results. Summary statistics for HCG assays from 46 women who had undergone bilateral tubal ligation represented baseline values. RESULTS: Pairwise agreement among the assessors for any of the three options ranged from 78-89%. At least three experts agreed for 147 cycles (96%), accounting for 28 conception losses and 19 continuing conceptions. The multi-rater kappa was 0.62 for the conception lost category and 0.68 for continuing conceptions, indicating substantial agreement. CONCLUSION: The main sources of disagreement involved deciding whether there was sufficient information for assessment, interpreting cycle parameters such as cycle length or bleeding event, and interpreting a distinct HCG rise pattern that does not exceed the baseline value obtained from the sterilized women.

Abortion, Spontaneous↗
PubMed2001

Natural limits of pregnancy testing in relation to the expected menstrual period.

CONTEXT: Pregnancy test kits routinely recommend testing "as early as the first day of the missed period." However, a pregnancy cannot be detected before the blastocyst implants. Due to natural variability in the timing of ovulation, implantation does not necessarily occur before the expected onset of next menses. OBJECTIVE: To estimate the maximum screening sensitivity of pregnancy tests when used on the first day of the expected period, taking into account the natural variability of ovulation and implantation. DESIGN AND SETTING: Community-based prospective cohort study conducted in North Carolina between 1982 and 1986. PARTICIPANTS: Two hundred twenty-one healthy women 21 to 42 years of age who were planning to conceive. MAIN OUTCOME MEASURES: Day of implantation, defined by the serial assay of first morning urine samples using an extremely sensitive immunoradiometric assay for human chorionic gonadotropin (hCG), relative to the first day of the missed period, defined as the day on which women expected their next menses to begin, based on self-reported usual cycle length. RESULTS: Data were available for 136 clinical pregnancies conceived during the study, 14 (10%) of which had not yet implanted by the first day of the missed period. The highest possible screening sensitivity for an hCG-based pregnancy test therefore is estimated to be 90% (95% confidence interval [CI], 84%-94%) on the first day of the missed period. By 1 week after the first day of the missed period, the highest possible screening sensitivity is estimated to be 97% (95% CI, 94%-99%). CONCLUSIONS: In this study, using an extremely sensitive assay for hCG, 10% of clinical pregnancies were undetectable on the first day of missed menses. In practice, an even larger percentage of clinical pregnancies may be undetected by current test kits on this day, given their reported assay properties and other practical limitations.

Adult↗
PubMed2001

Assessing human fertility using several markers of ovulation.

In modelling human fertility one ideally accounts for timing of intercourse relative to ovulation. Measurement error in identifying the day of ovulation can bias estimates of fecundability parameters and attenuate estimates of covariate effects. In the absence of a single perfect marker of ovulation, several error prone markers are sometimes obtained. In this paper we propose a semi-parametric mixture model that uses multiple independent markers of ovulation to account for measurement error. The model assigns each method of assessing ovulation a distinct non-parametric error distribution, and corrects bias in estimates of day-specific fecundability. We use a Monte Carlo EM algorithm for joint estimation of (i) the error distribution for the markers, (ii) the error-corrected fertility parameters, and (iii) the couple-specific random effects. We apply the methods to data from a North Carolina fertility study to assess the magnitude of error in measures of ovulation based on urinary luteinizing hormone and metabolites of ovarian hormones, and estimate the corrected day-specific probabilities of clinical pregnancy. Published in 2001 by John Wiley & Sons, Ltd.

Algorithms↗
PubMed2001

Placental abruption and perinatal mortality in the United States.

Placental abruption is an uncommon obstetric complication associated with high perinatal mortality rates. The authors explored the associations of abruption with fetal growth restriction, preterm delivery, and perinatal survival. The study was based on 7,508,655 singleton births delivered in 1995 and 1996 in the United States. Abruption was recorded in 6.5 per 1,000 births. Perinatal mortality was 119 per 1,000 births with abruption compared with 8.2 per 1,000 among all other births. The high mortality with abruption was due, in part, to its strong association with preterm delivery; 55% of the excess perinatal deaths with abruption were due to early delivery. Furthermore, babies in the lowest centile of weight (<1% adjusted for gestational age) were almost nine times as likely to be born with abruption than those in the heaviest (> or =90%) birth weight centiles. This relative risk progressively declined with higher birth weight centiles. After controlling for fetal growth restriction and early delivery, the high risk of perinatal death associated with abruption persisted. Even babies born at 40 weeks of gestation and birth weight of 3,500-3,999 g (where mortality was lowest) had a 25-fold higher mortality with abruption. The link between fetal growth restriction and abruption suggests that the origins of abruption lie at least in midpregnancy and perhaps even earlier.

Abruptio Placentae↗
PubMed2001

Survival and reproduction among males with birth defects and risk of recurrence in their children.

CONTEXT: Few systematic data exist on survival and reproduction among males with birth defects and their contribution to occurrence of birth defects in the next generation. OBJECTIVE: To estimate survival of males with registered birth defects, their subsequent reproduction rates, and their risk of transmitting birth defects to their offspring. DESIGN AND SETTING: Population-based cohort study of data from the Medical Birth Registry of Norway. SUBJECTS: A total of 486 207 males born in Norway between 1967 and 1982, 12 292 of whom had a recorded birth defect. MAIN OUTCOME MEASURES: Survival rates through 1992, reproduction rates through 1998, and risk of birth defects among offspring of males with vs without birth defects. RESULTS: Survival through 1992 was lower among males with birth defects (84% vs 97%). Compared with males without birth defects, affected males were 28% less likely to have had a child. Among offspring of affected males, 5.1% had a registered birth defect compared with 2.1% of offspring of males without birth defects (relative risk [RR], 2.4; 95% confidence interval [CI], 1.9-3.0). Offspring of affected fathers had an increased risk of the same defect as their fathers (RR, 6.5; 95% CI, 4.0-10.4) and an increased risk of dissimilar defects (RR, 1.8; 95% CI, 1.3-2.5). CONCLUSIONS: Compared with unaffected males, males with birth defects have higher mortality and survivors are less likely to have a child. Fathers with birth defects are significantly more likely than unaffected fathers to have an affected child.

Adolescent↗
PubMed2001

Likelihood of conception with a single act of intercourse: providing benchmark rates for assessment of post-coital contraceptives.

Emergency post-coital contraceptives effectively reduce the risk of pregnancy, but their degree of efficacy remains uncertain. Measurement of efficacy depends on the pregnancy rate without treatment, which cannot be measured directly. We provide indirect estimates of such pregnancy rates, using data from a prospective study of 221 women who were attempting to conceive. We previously estimated the probability of pregnancy with an act of intercourse relative to ovulation. In this article, we extend these data to estimate the probability of pregnancy relative to intercourse on a given cycle day (counting from onset of previous menses). In assessing the efficacy of post-coital contraceptives, other approaches have not incorporated accurate information on the variability of ovulation. We find that the possibility of late ovulation produces a persistent risk of pregnancy even into the sixth week of the cycle. Post-coital contraceptives may be indicated even when intercourse has occurred late in the cycle.

Coitus↗
PubMed2001

Sexual activity during late pregnancy and risk of preterm delivery.

OBJECTIVE: To examine the association between sexual activity during late pregnancy and preterm delivery. METHODS: Women at least 16 years old and carrying singleton fetuses were recruited between 24 and 29 weeks' gestation from prenatal clinics in central North Carolina. They were interviewed by telephone about sexual activity before and during pregnancy. One hundred eighty-seven women delivered between 29 and 36 weeks and had a follow-up interview after delivery. Four hundred nine women who were selected randomly from the cohort served as controls and had a follow-up interview between 29 and 36 weeks (mean gestational age 39.2 weeks). RESULTS: Intercourse during late pregnancy was associated with a reduced risk of preterm delivery. The conditional odds ratio (OR) was 0.34 and 95% confidence interval (CI) 0.23, 0.51 for preterm delivery within 2 weeks after intercourse. Similar decreased risk for preterm delivery was found with recent female orgasm. Adjusting for race, age, education, and living with a partner had little effect on results. Cases were more likely than controls to report poorer health, medical reasons for reducing sexual activity, less interest in sex, and receipt of advice to restrict sexual activity during pregnancy. Results did not differ substantially according to presence or absence of bacterial vaginosis at 28 weeks. CONCLUSION: These data provide evidence against the hypothesis that sexual activity generally increases risk of preterm delivery between 29 and 36 weeks. However, we cannot exclude the possibility that a small subgroup of susceptible women might have adverse consequences of sexual activity.

Adult↗
PubMed2001

Modelling multiple ovulation, fertilization, and embryo loss in human fertility studies.

Models of human fertility that incorporate information on timing of intercourse have assumed that a single ovum is released each menstrual cycle. These models are misspecified if two or more viable ova are sometimes released in a single cycle, which is known to occur in dizygotic twin pregnancies. In this paper, we propose a model for multiple ovulation in humans. We assume that the unobservable number of viable ova in each cycle follows a multinomial distribution. Successful fertilization of each ovum depends on the ability of the cycle to support a pregnancy and on the aggregate of a set of unobservable Bernoulli trials representing the fertilizing effects of intercourse on various days. Our model accommodates general covariate effects, allows for heterogeneity among couples, and accounts for a sterile subpopulation of couples. Information on early detection of pregnancy can be incorporated to estimate the probability of embryo loss. We outline a Markov chain Monte Carlo algorithm for estimation of the posterior distributions of the parameters. The methods are applied to data from a North Carolina pregnancy study, and applications to studies of assisted reproduction are described.

Journal Article↗
PubMed2001

On the importance--and the unimportance--of birthweight.

Birthweight is one of the most accessible and most misunderstood variables in epidemiology. A baby's weight at birth is strongly associated with mortality risk during the first year and, to a lesser degree, with developmental problems in childhood and the risk of various diseases in adulthood. Epidemiological analyses often regard birthweight as on the causal pathway to these health outcomes. Under this assumption of causality, birthweight is used to explain variations in infant mortality and later morbidity, and is also used as an intermediate health endpoint in itself. Evidence presented here suggests the link between birthweight and health outcomes may not be causal. Methods of analysis that assume causality are unreliable at best, and biased at worst. The category of 'low birthweight' in particular is uninformative and seldom justified. The main utility of the birthweight distribution is to provide an estimate of the proportion of small preterm births in a population (although even this requires special analytical methods). While the ordinary approaches to birthweight are not well grounded, the links between birthweight and a range of health outcomes may nonetheless reflect the workings of biological mechanisms with implications for human health.

Birth Weight↗
PubMed2000

The timing of the "fertile window" in the menstrual cycle: day specific estimates from a prospective study.

OBJECTIVES: To provide specific estimates of the likely occurrence of the six fertile days (the "fertile window") during the menstrual cycle. DESIGN: Prospective cohort study. PARTICIPANTS: 221 healthy women who were planning a pregnancy. MAIN OUTCOME MEASURES: The timing of ovulation in 696 menstrual cycles, estimated using urinary metabolites of oestrogen and progesterone. RESULTS: The fertile window occurred during a broad range of days in the menstrual cycle. On every day between days 6 and 21, women had at minimum a 10% probability of being in their fertile window. Women cannot predict a sporadic late ovulation; 4-6% of women whose cycles had not yet resumed were potentially fertile in the fifth week of their cycle. CONCLUSIONS: In only about 30% of women is the fertile window entirely within the days of the menstrual cycle identified by clinical guidelines-that is, between days 10 and 17. Most women reach their fertile window earlier and others much later. Women should be advised that the timing of their fertile window can be highly unpredictable, even if their cycles are usually regular.

Estrogens↗
PubMed2000

Urinary oestrogen patterns in long follicular phases.

Long menstrual cycles have been associated with reduced risk of breast cancer and increased risk of osteoporosis. These observations have led to assumptions about the endogenous oestrogen exposure of women with long cycles. However, daily oestrogen profiles in long menstrual cycles have not been described. This paper examines daily urinary oestrogen profiles during the follicular phases of 416 conception and non-conception cycles. Women were aged 21-42 years, had no history of infertility and were not under treatment. Twenty-eight cycles were defined as long, with a follicular phase that lasted 24 days or more. Five patterns were observed among these long cycles, the most common being a pattern consistent with delayed emergence of a dominant follicle. Other patterns were a pattern consistent with demise and replacement of a dominant follicle, one consistent with delayed follicular recruitment, one showing a prolonged initial drop in oestrogen and one with an extended oestrogen peak. Average follicular phase oestrogen concentrations were highest in cycles with short follicular phases (7-11 days). Oestrogen concentrations from long follicular phases (24-59 days) did not differ substantially from follicular phases of usual length (12-17 days). The oestrogen profiles in long follicular phases are heterogeneous and not necessarily hypo-oestrogenic.

Adult↗
PubMed1999

The quest for better questionnaires.

The development of questionnaires is a neglected enterprise in epidemiology. It has recently been proposed that a prestigious health authority such as the World Health Organization establish a committee to tackle issues of questionnaire quality, moving eventually toward standardized instruments. However, standardization may not be the best way to invigorate this enterprise. As an alternative, the author suggests that the first step in improving questionnaires would be to make them more accessible. Ideally, questionnaires should be as easily scrutinized as a study's methods or results. To this end, the author suggests that when a research paper is published, the entire questionnaire be made available on the worldwide web. Electronic access to questionnaires could stimulate a new era of awareness about the importance of questionnaire design.

Data Collection↗
PubMed1999

Time of implantation of the conceptus and loss of pregnancy.

BACKGROUND: Implantation of the conceptus is a key step in pregnancy, but little is known about the time of implantation or the relation between the time of implantation and the outcome of pregnancy. METHODS: We collected daily urine samples for up to six months from 221 women attempting to conceive after ceasing to use contraception. Ovulation was identified on the basis of the ratio of urinary estrogen metabolites to progesterone metabolites, which changes rapidly with luteinization of the ovarian follicle. The time of implantation was defined by the appearance of chorionic gonadotropin in maternal urine. RESULTS: There were 199 conceptions, for 95 percent of which (189) we had sufficient data for analysis. Of these 189 pregnancies, 141 (75 percent) lasted at least six weeks past the last menstrual period, and the remaining 48 pregnancies (25 percent) ended in early loss. Among the pregnancies that lasted six weeks or more, the first appearance of chorionic gonadotropin occurred 6 to 12 days after ovulation; 118 women (84 percent) had implantation on day 8, 9, or 10. The risk of early pregnancy loss increased with later implantation (P<0.001). Among the 102 conceptuses that implanted by the ninth day, 13 percent ended in early loss. This proportion rose to 26 percent with implantation on day 10, to 52 percent on day 11, and to 82 percent after day 11. CONCLUSIONS: In most successful human pregnancies, the conceptus implants 8 to 10 days after ovulation. The risk of early pregnancy loss increases with later implantation.

Abortion, Spontaneous↗