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Allen J Wilcox

Publications and source records attributed to Allen J Wilcox.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence of duplications and deletions of the 22q11 DiGeorge syndrome region in a population-based sample of infants with cleft palate.

The prevalence of duplications and deletions of the 22q11.2 (DiGeorge syndrome) region was studied among babies born in Norway with open cleft palate without cleft lip (cleft palate only, CPO). During a 5-year period (1996-2001), there were 245 live births with CPO that were referred for surgery. DNA was available from 174 cases with overt cleft palate. DNA copy number was analyzed with the multiplex ligation-dependent probe amplification (MLPA) technique, and an unambiguous result was obtained in 169 (97%) of the samples. We found no 22q11.2 duplications, and one known, and two previously undiagnosed cases with 22q11.2 deletions. All three del22q11-syndrome cases also had heart malformations, which represent one-third of the 10 babies with heart malformations in our study population. The prevalence of del22q11-syndrome among babies with cleft palate with or without additional malformations was 1 of 57 (1.8%). Because the prevalence of CPO in the 35 22q11.2 duplication cases published was 20%, we also investigated if dup22q11-testing was warranted in this group. However, no 22q11.2 duplications were found, indicating that the duplication cases ascertained so far might not be representative of the dup22q11-group as a whole. We conclude that neither del22q11 nor dup22q11 testing is warranted in babies with overt cleft palate as the only finding.

Chromosome Deletion↗
PubMed2006

Can men provide accurate confounder data about their partners for Time-to-Pregnancy studies?

PURPOSE: In studies of time to pregnancy (TTP), women's health-related behaviors may confound other determinants of TTP. In many occupation-based TTP studies, all information is collected through the male partner. There are no data on the validity of the man's report of his partner's fertility-related behavior. METHODS: We studied 202 men and their partners from the most recent pregnancy. Validity of men's reporting on their partner's use of oral contraceptives (OCs) as the last birth control method and her smoking around the beginning of TTP and agreement of coital frequency were assessed. RESULTS: The index pregnancy was an average of 6 years before interview. Overall percentage of agreement was 81% for OCs as the last contraceptive method (kappa agreement = 0.44). Ninety-five percent of men accurately reported whether their partner smoked (kappa agreement = 0.83). Among couples agreeing on smoking status, 90% agreed on the categorical cigarette number (weighted kappa = 0.60). Reporting accuracy was not influenced by men's characteristics. Median coital frequency was eight times per month, with a weighted kappa = 0.34 after categorization. CONCLUSIONS: Our data generally justify the use of men's reports of potential confounders in TTP studies when women's reports are not available.

Adult↗
PubMed2006

Trends in fetal and infant survival following preeclampsia.

CONTEXT: Management of preeclampsia often culminates in induced delivery of a very preterm infant. While early termination protects the fetus from an intrauterine death, the newborn then faces increased risks associated with preterm delivery. This practice has increased in recent decades, but its net effect on fetal and infant survival has not been assessed. OBJECTIVE: To assess the effect on fetal and infant survival of increased rates of early delivery of preeclamptic pregnancies. DESIGN, SETTING, AND PARTICIPANTS: Population-based observational longitudinal study using registry data from 804 448 singleton first-born infants with Norwegian-born mothers and registered in the Medical Birth Registry of Norway between 1967 and 2003. MAIN OUTCOME MEASURES: Odds ratio (OR) of fetal and early childhood death in relation to preeclampsia. RESULTS: Among preeclamptic pregnancies, inductions before 37 weeks increased from 8% in 1967-1978 to nearly 20% in 1991-2003. During this period, the adjusted OR for stillbirth decreased from 4.2 (95% confidence interval [CI], 3.8-4.7) to 1.3 (95% CI, 1.1-1.7) for preeclamptic compared with nonpreeclamptic pregnancies. During the same period, the OR for neonatal death after preeclamptic pregnancy remained relatively stable (1.7 in 1967-1978 vs 2.0 in 1991-2003). Later infant and childhood mortality also showed little change. CONCLUSIONS: Fetal survival in preeclamptic pregnancies has vastly improved over the past 35 years in Norway, presumably because of more aggressive clinical management. However, the relative risk of neonatal death following a preeclamptic pregnancy has not changed over time.

Cesarean Section↗
PubMed2006

Invited commentary: the perils of birth weight--a lesson from directed acyclic graphs.

The strong association of birth weight with infant mortality is complicated by a paradoxical finding: Small babies in high-risk populations usually have lower risk than small babies in low-risk populations. In this issue of the Journal, Hernández-Díaz et al. (Am J Epidemiol 2006;164:1115-20) address this "birth weight paradox" using directed acyclic graphs (DAGs). They conclude that the paradox is the result of bias created by adjustment for a factor (birth weight) that is affected by the exposure of interest and at the same time shares causes with the outcome (mortality). While this bias has been discussed before, the DAGs presented by Hernández-Díaz et al. provide more firmly grounded criticism. The DAGs demonstrate (as do many other examples) that seemingly reasonable adjustments can distort epidemiologic results. In this commentary, the birth weight paradox is shown to be an illustration of Simpson's Paradox. It is possible for a factor to be protective within every stratum of a variable and yet be damaging overall. Questions remain as to the causal role of birth weight.

Causality↗
PubMed2006

Birth weight and mortality: causality or confounding?

The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality.

Birth Weight↗
PubMed2006

Maternal and paternal influences on length of pregnancy.

OBJECTIVE: Biological evidence suggests that both mother and fetus are involved in triggering a normal delivery. A tendency of a child to have a gestational age at birth similar to the father's could represent the effect of genes passed from the father to the fetus. Similar tendencies between mother and child could represent maternal genes passed to the fetus, as well as genes to the mother received from the grandmother that affect a woman's capacity to carry a pregnancy. METHODS: The Medical Birth Registry of Norway contains data on all births in Norway from 1967 onward. We identified 77,452 pairs of boys and girls born at term who later became parents and linked their birth data to the birth records for their first child. RESULTS: Gestational age of the child at birth increased on average 0.58 days for each additional week in the father's gestational age (95% confidence interval 0.48-0.67) and 1.22 days for each additional week in the mother's gestational age (1.21-1.32). Gestational age was, however, 0.65 days reduced for each additional kilogram in the father's birth weight, presumably due to more rapid growth of the fetus triggering delivery. CONCLUSION: Initiation of delivery has a fetal component that is heritable (passed from father and mother to child) and an additional maternal component that is also heritable. In addition, a more rapid rate of fetal growth appears to trigger delivery at earlier gestation. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2006

Paternal age and delivery before 32 weeks.

BACKGROUND: Advanced paternal age has been linked to early preterm delivery (before 32 weeks). METHODS: We analyzed live births from white, non-Hispanic primiparas recorded in U.S. birth certificates from 1995 to 2000 (excluding California). We examined 2,509,012 pregnancies of married women 20 to 34 years old, excluding unmarried women due to the high fraction of missing data on father's age. We defined the outcome according to the clinical estimate of gestation after excluding unlikely birth weights, because the estimate based on last menstrual period is particularly prone to errors at early gestations. RESULTS: Older paternal age was not associated with increased risk of early preterm delivery. The highest estimated odds ratio among fathers 50 years or older was 1.3 (95% confidence interval = 0.6-2.8) among women 20 to 24 years old. CONCLUSIONS: These U.S. data do not support an association between advanced paternal age and delivery before 32 weeks.

Adult↗
PubMed2005

Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort.

OBJECTIVES: To assess the impact on risk of pre-eclampsia of genes that work through the mother, and genes of paternal origin that work through the fetus. DESIGN: Population based cohort study. SETTING: Registry data from Norway. PARTICIPANTS: Linked generational data from the medical birth registry of Norway (1967-2003): 438,597 mother-offspring units and 286,945 father-offspring units. MAIN OUTCOME MEASURES: Pre-eclampsia in the second generation. RESULTS: The daughters of women who had pre-eclampsia during pregnancy had more than twice the risk of pre-eclampsia themselves (odds ratio 2.2, 95% confidence interval 2.0 to 2.4) compared with other women. Men born after a pregnancy complicated by pre-eclampsia had a moderately increased risk of fathering a pre-eclamptic pregnancy (1.5, 1.3 to 1.7). Sisters of affected men or women, who were themselves born after pregnancies not complicated by pre-eclampsia, also had an increased risk (2.0, 1.7 to 2.3). Women and men born after pre-eclamptic pregnancies were more likely to trigger severe pre-eclampsia in their own (or their partner's) pregnancy (3.0, 2.4 to 3.7, for mothers and 1.9, 1.4 to 2.5, for fathers). CONCLUSIONS: Maternal genes and fetal genes from either the mother or father may trigger pre-eclampsia. The maternal association is stronger than the fetal association. The familial association predicts more severe pre-eclampsia.

Birth Order↗
PubMed2005

Cleft lip and palate versus cleft lip only: are they distinct defects?

Cleft lip defects are usually regarded as a single entity, with the assumption that an accompanying cleft palate represents the more severe form. The authors linked data from the Medical Birth Registry of Norway with medical records from two centralized centers to provide a population-based data set. They assessed the distribution of cleft lip only and cleft lip with cleft palate by covariate. Among 1.8 million Norwegian livebirths between 1967 and 1998, there were 1,572 cases of cleft lip with cleft palate and 1,122 cases with cleft lip only. Seventeen percent of those with cleft lip and palate had another defect compared with 9% of those with cleft lip only. For boys, the risk was greater for cleft lip and palate than for cleft lip only (odds ratio=2.4 vs. 1.8, p<0.001 for difference). The risk of cleft lip only, but not of cleft lip and palate, was increased for twins (odds ratio=1.6 vs. 1.1, p=0.11) and infants whose parents were first cousins (odds ratio=2.7 vs. 0.7, p=0.07). Although cleft lip with cleft palate may simply represent a more severe form of the defect, epidemiologic assessments of cleft lip should, when possible, include separate analyses of these two groups.

Abnormalities, Multiple↗
PubMed2005

Intact HCG, free HCG beta subunit and HCG beta core fragment: longitudinal patterns in urine during early pregnancy.

BACKGROUND: Detecting and monitoring early pregnancy depend on the measurement of HCG. Little is known about how production of various forms of HCG may evolve over the earliest weeks of pregnancy, particularly in naturally conceived pregnancies. METHODS: We describe the daily excretion of three urinary HCG analytes during the first 6 weeks post-conception in 37 naturally conceived pregnancies ending in singleton birth. We assayed daily first morning urine samples for intact HCG, free beta subunit and beta?core fragment, plus the combined measurement of these HCG forms. We calculated doubling times for each analyte and the inter- and intra-subject day-to-day variation. RESULTS: Intact HCG and the free beta subunit were initially the predominant forms of HCG, with the beta core fragment emerging as the predominant form in the fifth week after conception. Intact HCG and the free beta subunit showed the most day-to-day variability, and were transiently undetectable even 10 days after detection of pregnancy. The most stable estimate of doubling time was provided by the combined measurement of all these forms. CONCLUSIONS: Although intact HCG is usually regarded as the main analyte for detection and monitoring of early pregnancy, it can fluctuate markedly during early pregnancy. This variability could affect pregnancy test results based on early pregnancy urine, and may distort estimates of doubling time. Assays that combine several forms of HCG may be more reliable.

Adult↗
PubMed2005

Has human fertility declined over time?: why we may never know.

BACKGROUND: Reports of decreased semen quality over time have raised concerns about possible reductions in human fertility. Studies of couple fertility have produced conflicting results. We evaluate how changes in the availability and use of effective contraception and induced abortion might bias the direct study of time trends in couple fertility. METHODS: We assess the potential for bias in the context of 2 common study designs: (1) a study of time-to-pregnancy that estimates fecundability (excluding unintended pregnancies) and (2) a study of infertility rates that categorizes couples as fertile or infertile (including couples with unintended pregnancies as fertile). RESULTS: In time-to-pregnancy studies, bias alone could produce more than a 2-fold apparent increase in fecundability over recent decades. In studies of infertility rates, the bias works in the opposite direction: a 30% underestimation of infertility during earlier decades could produce an apparent decrease in fertility over time. CONCLUSIONS: Over the past 5 decades, changes in social factors that affect the rate and fate of unintended pregnancies could substantially bias time trends in fertility. These biases may explain the conflicting reports in the literature. Except in rare settings in which the factors affecting reproductive choices have not changed, it is probably impossible to identify biologic changes in fertility over recent decades.

Abortion, Induced↗
PubMed2005

Terms in reproductive and perinatal epidemiology: 2. Perinatal terms.

This is the second of a two part glossary of terms used in reproductive and perinatal epidemiology. The purpose is to provide a reference for terms that are widely (if not always consistently) used in this field. While a glossary cannot resolve all these problems, it provides a point of reference for understanding them. Part 1 covered terms relevant mostly to events and conditions before birth. Part 2 emphasises terms used during the time around and after birth.

Perinatology↗
PubMed2004

Height and risk of severe pre-eclampsia. A study within the Danish National Birth Cohort.

BACKGROUND: Pre-eclampsia shares a number of risk factors with cardiovascular disease (CVD). Women with recurrent pre-eclampsia or pre-eclampsia early in pregnancy reportedly have an increased long-term risk of CVD. Short stature is a risk factor for CVD but has rarely been examined in relation to pre-eclampsia. METHODS: We used data from 59 968 singleton live births in the Danish National Birth Cohort born between 1998 and 2001 to assess risk of severe pre-eclampsia/eclampsia (296 cases) in relation to self-reported height. We examined the association in multiple logistic regressions stratified by parity. RESULTS: Among primiparas there was a weak association (compared with women <165 cm, women >172 cm had on OR of 0.79, 95% CI: 0.55, 1.14). Among multiparas, the tallest women had an adjusted OR of 0.42 (95% CI: 0.20, 0.87) of developing severe pre-eclampsia compared with women <165 cm. The OR per centimetre was 0.94 (95% CI: 0.91, 0.97). Self-reported pre-existing hypertension did not explain this association, which also persisted when the analysis was restricted to non-overweight women. CONCLUSIONS: Short stature was associated with a higher risk of severe pre-eclampsia in multiparas participating in the Danish National Birth Cohort.

Body Height↗
PubMed2004

Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology.

BACKGROUND: There has been increasing number of pregnancies following assisted reproductive technology treatment and their survival is understandably a matter of interest. The relative risk of spontaneous abortion in these pregnancies remains unclear. The objectives of this study were to quantify the relative risk in assisted reproductive technology pregnancies in relation to two cohorts of naturally conceived pregnancies and to assess the possible risk factors for spontaneous abortion among assisted reproductive technology pregnancies. METHODS: Three cohorts of pregnancies, 1945 pregnancies conceived following assisted reproductive technology treatment in a tertiary infertility clinic, 549 natural pregnancies in a prospective study of lifestyle and pregnancy (the Ford cohort), and 4265 pregnancies from another cohort (the Treloar cohort), were used in the study. RESULTS: After adjusting for age, the relative risk of spontaneous abortion was 1.20 (95% CI 1.03-1.46) in the assisted reproductive technology cohort in comparison with the Ford cohort. Within the assisted reproductive technology cohort, a history of spontaneous abortion predicted increased risk, while a low level of ovarian stimulation seemed to be related to a reduced risk. CONCLUSIONS: The study showed that the risk of spontaneous abortion was slightly increased in the assisted reproductive technology pregnancies after adjusting for maternal age and previous spontaneous abortion. Within the assisted reproductive technology cohort, several variables, including the level of stimulation, appeared to be linked with the risk of spontaneous abortion.

Abortion, Spontaneous↗