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Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project.

This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.

Adolescent↗

Variation in female breast cancer risk by occupation.

Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age of first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only "administrative support occupations" had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% CI 1.06-1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated.

Administrative Personnel↗

Bone mineral density of the total body and forearm in premenopausal black and white women.

This study was conducted to report and compare bone mineral density (BMD) of the total body and distal forearm, as measured by X-ray absorptiometry, in 65 black and 73 white premenopausal women between the ages of 20 and 40. The black women had higher current and recalled body weights, a higher percent body fat, and more pregnancies and births, were younger at menarche, and reported lower alcohol intakes than the white women studied. A smaller percent of the black women had experienced amenorrhea, and a higher percent had lived at southern latitudes. Smoking history and lifetime use of oral contraceptives were similar in the two groups. Total body BMD, adjusted for body mass index (BMI), was 5.9% higher in the black than in the white women [mean +/- standard deviation (SD): 1.230 +/- 0.076 g/cm2 compared with 1.161 +/- 0.075; difference (95% confidence interval [CI95]: 0.068 (0.042, 0.095)]. Forearm BMD, adjusted for BMI, was 9.3% higher in the black women [mean +/- SD: 0.505 +/- 0.046 compared with 0.462 +/- 0.045; difference (CI95): 0.043 (0.027, 0.059)]. Adjustment for the other medical and lifestyle differences noted before had little effect on estimated BMD differences between the two groups.

Absorptiometry, Photon↗

Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE study.

OBJECTIVES: To evaluate the risk of very preterm birth (22-32 weeks of gestation) associated with previous induced abortion according to the complications leading to very preterm delivery in singletons. DESIGN: Multicentre, case-control study (the French EPIPAGE study). SETTING: Regionally defined population of births in France. SAMPLE: The sample consisted of 1943 very preterm live-born singletons (< 33 weeks of gestation), 276 moderate preterm live-born singletons (33-34 weeks) and 618 unmatched full-term controls (39-40 weeks). METHODS: Data from the EPIPAGE study were analysed using polytomous logistic regression models to control for social and demographic characteristics, lifestyle habits during pregnancy and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, fetal growth restriction, premature rupture of membranes, idiopathic preterm labor and other causes. MAIN OUTCOME MEASURES: Odds ratios for very preterm birth by gestational age and by pregnancy complications leading to preterm delivery associated with a history of induced abortion. RESULTS: Women with a history of induced abortion were at higher risk of very preterm delivery than those with no such history (OR + 1.5, 95% CI 1.1-2.0); the risk was even higher for extremely preterm deliveries (< 28 weeks). The association between previous induced abortion and very preterm delivery varied according to the main complications leading to very preterm delivery. A history of induced abortion was associated with an increased risk of premature rupture of the membranes, antepartum haemorrhage (not in association with hypertension) and idiopathic spontaneous preterm labour that occur at very small gestational ages (< 28 weeks). Conversely, no association was found between induced abortion and very preterm delivery due to hypertension. CONCLUSION: Previous induced abortion was associated with an increased risk of very preterm delivery. The strength of the association increased with decreasing gestational age.

Abortion, Induced↗

Incomplete pregnancies and risk of ovarian cancer (Washington, United States).

Because of the reduced risk of ovarian cancer related to prior full-term pregnancies, we sought to determine whether there was any association with a history of one or more incomplete pregnancies. White female residents of three counties in Washington State (United States) diagnosed with ovarian cancer during 1986-88 (n = 322), and a random sample of control women selected from these same counties (n = 426), were interviewed regarding their pregnancy and childbearing histories. Among women who had given birth to at least one child, an additional incomplete pregnancy was not associated with the risk of ovarian cancer (relative risk [RR] = 1.1, 95 percent confidence interval [CI] = 0.8-1.6, adjusting for age, oral contraceptive use, and number of births). For those who had never given birth, a somewhat smaller proportion of cases had a history of incomplete pregnancy than controls (RR = 0.8, CI = 0.4-1.7). In an analysis restricted to ever-pregnant women, a prior induced or spontaneous abortion was not found to be associated with the incidence of ovarian tumors (RR = 1.0, CI = 0.6-1.7, and RR = 1.3, CI = 0.8-1.9, respectively). Other studies of the possible relation between incomplete pregnancies and ovarian cancer generally have observed either a weak negative association or no association at all. It is possible that if incomplete pregnancies do affect the risk of ovarian cancer, their impact might be too small to be identified reliably through epidemiologic studies.

Abortion, Induced↗

Factors determining admission to neonatal units in Jamaica.

In order to identify the factors associated with admission to neonatal care units in a developing country, 1,823 newborns admitted to Jamaica's eight neonatal care units over a 6-month period were compared with 9,563 newborns identified during an island-wide population morbidity study. Maternal sociodemographic characteristics, past obstetric history, infant's growth parameters at birth and mode and place of delivery were investigated. Babies of mothers resident in the two regions of the island where specialist paediatric services were available had increased odds of admission (OR= 1.45, 1.22) compared with those living elsewhere (OR=0.70, 0.80). Maternal history of a previous miscarriage, termination or early neonatal death were associated with subsequent admission, but a previous stillbirth or late neonatal death were not. Very low birthweight infants of gestational age 28-31 weeks were more likely to be admitted than those < 28 weeks with ORs of 1.45 and 0.34 respectively. Factors determining neonatal admission in the developing world may be quite different from those of developed countries. The development of guidelines and support services to ensure wider access to these services for those most in need could contribute to more equitable utilisation of services.

Adult↗

The human capital study 2002-04: tracking, data collection, coverage, and attrition.

Between 2002 and 2004, the Institute of Nutrition of Central America and Panama (INCAP), in collaboration with Emory University, the International Food Policy Research Institute (IFPRI), and the University of Pennsylvania, re-surveyed young Guatemalan adults who had, as children, been participants in a nutrition supplementation trial conducted by INCAP between 1969 and 1977. This "Human Capital Study 2002-04" complements and extends data obtained in previous studies by collecting new information on measures of physical health and well-being, schooling and cognitive ability, wealth, consumption and economic productivity, and marriage and fertility histories. This paper describes the study domains and data collection procedures. Among 2,393 members of the original sample, 1,856 (77%) were targets for enrollment. Response rates varied by gender, current place of residence, and domain of data collection, with 80% of males and 89% of females completing at least one data collection instrument. Attrition was not random and appears to be associated with a number of initial characteristics of individuals and their households that should be controlled for in future analyses. We conclude that data collection was successful and data quality is high, facilitating the successful undertaking of our planned investigation of important study hypotheses.

Adult↗

T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region.

Recurrent pregnancy loss (RPL) is a common disorder during early gestation. Recent evidence suggests that T helper 1 (Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RPL of otherwise unknown etiology, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-1 may influence Th1/Th2 immune responsiveness and has been implicated in the establishment of successful pregnancy. In the present study, we investigated polymorphism of the IL-1beta gene (IL1B) in women with a history of RPL. Significant increases in the frequencies of IL1B promoter region variants IL1-511C and IL1B-31T were found in women with a history of RPL. Increased frequencies of these two variants and their homozygotes were found only in cases having evidence of Th1 immunity to trophoblast as determined by IFN-gamma production of peripheral blood mononuclear cells (PBMCs) stimulated with a trophoblast cell-line extract. Significantly higher IFN-gamma production by PBMCs in response to trophoblast correlated with variant IL1B-511C and its homozygocity in women with RPL. These results suggest that variants -511C and -31T in the IL1B promoter region confer risk for RPL associated with Th1 immunity to trophoblast antigens.

Abortion, Habitual↗

[Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina].

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43%, Guarani indians: 60%, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23%) and low risk (6 y 11: 12%) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9% in urban women and 29% in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

Adolescent↗

Primary dysmenorrhea and risk of preterm delivery.

Little is known about the mechanism and biochemical pathway of preterm delivery. Some drugs used to treat preterm labor are also useful for the treatment of primary dysmenorrhea. This study attempted to evaluate the association between primary dysmenorrhea and preterm delivery from an epidemiological perspective. A nested case-control study was conducted; 329 singleton preterm delivery cases were investigated, in aggregate and in subgroups (spontaneous preterm labor and preterm premature rupture of membranes). Concurrently, 329 singleton gravid women with term delivery served as controls. Medical charts and records provided information about the maternal history of dysmenorrhea, index pregnancy outcome, and demographic characteristics. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the multiple logistic regression method. Gravid women with a history of primary dysmenorrhea had no more risk of preterm delivery than those without a history of primary dysmenorrhea (adjusted OR, 1.16; 95% CI, 0.95 to 2.19; p=0.37). However, for subgroup analysis, gravid women with severe primary dysmenorrhea were associated with an adjusted 2.73-fold risk of spontaneous preterm delivery (95% CI, 1.49 to 4.95; p=0.02), and with an adjusted 1.51-fold risk of preterm premature rupture of membranes (95% CI, 0.68 to 3.22; p=0.31). Severe primary dysmenorrhea is associated with an increased risk of spontaneous preterm delivery. A common pathophysiologic pathway may exist between these two disorders. Further in-depth biochemical and molecular studies are necessary to explore this phenomenon.

Adult↗

Infants of Mexican immigrants. Health status of an emerging population.

Previous studies suggest that infants of Mexican immigrants have favorable birth outcomes despite their high socioeconomic risks. These favorable outcomes have been associated with a protective sociocultural orientation among immigrants. A sample of 708 infants of Mexican origin was assessed to determine whether such health advantages at birth are sustained at 8 to 16 months of age, or alternatively, whether their health deteriorates because of adverse socioeconomic conditions. A a cross-sectional survey was conducted in San Diego County to determine whether the child was healthy or ill (the latter indicating a history of serious infectious disease) and the factors associated with this outcome. Among infants born without serious medical problems, 74% remained healthy. For 26% of the infants, their health status was eroded by social conditions. Factors associated with illness were large households, barriers to care, and maternal characteristics including smoking, pregnancy complications, and employment. Women born in Mexico who were newcomers to the United States and spoke Spanish exclusively were more likely than non-newcomers to have ill children. In this population, one fourth of Latino infants of immigrants were at high risk for serious infectious disease despite using preventive care.

Adolescent↗

Primary predictors of preterm labour.

Spontaneous preterm birth accounts for 60% of all preterm births in developed countries. With the increase in multiple pregnancies, induced preterm birth and the progress in neonatal care for extremely preterm neonates, spontaneous preterm birth for singleton pregnancies in developed countries has probably decreased over the past 30 years. This decrease is likely to be related to better prenatal care for all pregnant women because the recognition of primary risk factors in early or late pregnancy remains a basic part of prenatal care. The failure to distinguish between induced and spontaneous preterm labour in most population-based studies makes it difficult to interpret results with respect to the primary predictors of preterm labour. Many such primary predictors of preterm labour have been used over the past 20-30 years. These include individual factors, socio-economic factors, working conditions and obstetric and gynaecological history. Risk scores have been proposed in order to produce these data. Unfortunately, the predictive value of these scores, especially their specificity, is poor, mainly because all of these factors are indirect. We still cannot identify the mechanisms that lead to preterm labour and birth. New markers more directly related to preterm labour have recently been proposed, some of which relate to direct causes of preterm labour such as cervical ultrasound measurement, fetal fibronectin (FFN), salivary estriol, serum CRH and bacterial vaginosis. Several of these have predictive values, which are potentially useful for clinical practice. Nonetheless, pregnant women in developed countries are already closely monitored throughout pregnancy. Before proposing new screening tests to be applied systematically to all pregnant women, their advantages and drawbacks must be fully evaluated.

Biomarkers↗

Gynaecological and obstetric disorders in coeliac disease: frequent clinical onset during pregnancy or the puerperium.

BACKGROUND AND AIM: While gynaecological and obstetric disorders have been reported among women with coeliac sprue, their true prevalence and relationship to the coeliac disease process has not been completely elucidated. Our aims were to determine: (1) the prevalence of gynaecological and obstetric problems in patients with coeliac disease and the influence of strict gluten restriction on their occurrence, (2) the effect of pregnancy on the clinical course of coeliac disease and (3) the clinical features of those patients with onset of coeliac disease during pregnancy and the puerperium. PATIENTS AND METHODS: The gynaecological and obstetric history of 130 coeliac patients and 130 age-matched healthy female controls were compared in a case-control study. RESULTS: In comparison to the controls, untreated coeliac disease patients exhibited significantly later menarche, an earlier menopause, an increased prevalence of secondary amenorrhoea and a greater incidence of spontaneous abortions. Patients who had adhered, in the long term, to a gluten-free diet had gynaecological and obstetric history indistinguishable from controls. Clinical deterioration of coeliac disease was observed in untreated patients during 17% of their pregnancies. In 14% of those untreated patients who were pregnant symptoms related to coeliac disease were manifested for the first time during either pregnancy (n = 7) or the puerperium (n = 4). Nine of these patients had underestimated features suggestive of coeliac disease. CONCLUSION: The early diagnosis and treatment of coeliac disease may avoid significant gynaecological and obstetric complications in affected women. Celiac sprue must always be borne in mind among patients who develop diarrhoea and weight loss during pregnancy and/or the puerperium.

Abortion, Spontaneous↗

Fetal macrosomia at the University College Hospital, Ibadan: a 3-year review.

The study aimed to determine the maternal characteristics and contribution to obstetric morbidity of infants presenting with fetal macrosomia at the University College Hospital, Ibadan. This was a retrospective study. Obstetric data of the mothers were extracted from the casenotes and analysed. Fetal characteristics such as sex and weight, and perinatal complication were also analysed. The maternal characteristics that were significantly different in the study and control groups were parity, term weight >/= 90 kg, previous history of fetal macrosomia and mean duration of pregnancy. There was no significant difference in maternal age or height. The incidence of caesarean section was three times more common in the study group. There were three cases of shoulder dystocia in the study group but none in the control group. The mean birth weight of macrosomic babies delivered by section or macrosomic babies that died was higher than the mean birth weight of macrosomic babies delivered per vagina or that survived. Severe asphyxia at 1 minute was significantly higher in the study group. Perinatal mortality among macrosomic babies was 11.4/1,000. There was no mortality in the control group. It is suggested that clinical suspicion of macrosomic based on risk factors such as those identified in this study may be found useful in antenatal prediction.

Acute-Phase Proteins↗

Characterization of patients with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO).

BACKGROUND: Osteoporotic fractures remain a major public health problem. Currently available osteoporosis therapies significantly reduce the risk of fractures, but up to 50% of patients have an inadequate clinical outcome to therapy. AIM: To describe the clinical and quality of life (QOL) of a study population meeting a proposed definition of inadequate clinical outcome to osteoporosis therapy, recruited for the Observational Study of Severe Osteoporosis (OSSO). DESIGN: Cross-sectional, observational study. METHODS: Post-menopausal women with osteoporosis (n = 2314) were divided into Group 1 (those who had previously experienced a fragility fracture despite osteoporosis drug therapy for at least 12 months) (n = 1309, 57%), or Group 2 (those who had previously discontinued osteoporosis drug therapy due to non-compliance or side-effects) (n = 1005; 43%). Baseline clinical characteristics, quality of life (QOL) and osteoporosis/falls risk factors were analysed. RESULTS: The overall population had low BMD (mean +/- SD T-score at lumbar spine -3.1 +/- 1.1), and risk factors for fracture such as previous fractures (67.8%), family history (15.1%), and prolonged glucocorticoid use (17.5%). QOL was poor: total QUALEFFO and EQ-5D scores were 46.8 +/- 18.7, and 0.50 +/- 0.33, respectively. Patients in Group 1 had higher age and body mass index, fewer hours of exercise, more previous fragility fractures and falls, and poorer QOL scores. DISCUSSION: Our definition of inadequate clinical outcome from osteoporosis drug therapy identifies a severe osteoporosis cohort with poor QOL and increased fracture risk. Using such a definition may lead to earlier recognition of inadequate clinical outcome to osteoporosis therapy, and improved interventions and results.

Absorptiometry, Photon↗

Spontaneous abortion--high risk factor for neural tube defects in subsequent pregnancy.

An increased spontaneous abortion rate has been observed in pregnancies preceding that of fetuses or newborn infants with neural tube defects (NTDs). There are 2 suggested explanations for this observation. One is that a trophoblastic cell rest, remaining from a previous aborted pregnancy, interferes with normal embryogenesis. The second is that the previous lost fetus was affected with NTD. We studied the obstetric history of mothers of newborn infants with NTDs compared to those with other birth defects, in low and high risk groups for NTD (Jew and Bedouins). A significantly higher spontaneous abortion rate (48%) in the preceding pregnancy was found in the NTD group compared to the group with other birth defects (20%). This was especially remarkable for spina bifida cases in the Jewish study population. A significantly higher rate of preceding spontaneous abortion was also found in congenital heart defects (CHD) when compared to other congenital malformations. A hypothesis based on the multifactorial threshold model is put forward to explain these findings. Based on the realization that spontaneous abortion constitutes a high risk factor for NTD and possibly also CHD, we recommend a delay of subsequent pregnancy and periconceptional treatment with folic acid following spontaneous abortion.

Abortion, Spontaneous↗

Evolutionary history of lorisiform primates.

We integrate information from the fossil record, morphology, behavior and molecular studies to provide a current overview of lorisoid evolution. Several Eocene prosimians of the northern continents, including both omomyids and adapoids, have been suggested as possible lorisoid ancestors, but these cannot be substantiated as true strepsirhines. A small-bodied primate, Anchomomys, of the middle Eocene of Europe may be the best candidate among putative adapoids for status as a true strepsirhine. Recent finds of Eocene primates in Africa have revealed new prosimian taxa that are also viable contenders for strepsirhine status. Plesiopithecus teras is a Nycticebussized, nocturnal prosimian from the late Eocene, Fayum, Egypt, that shares cranial specializations with lorisoids, but it also retains primitive features (e.g. four premolars) and has unique specializations of the anterior teeth excluding it from direct lorisiform ancestry. Another unnamed Fayum primate resembles modern cheirogaleids in dental structure and body size. Two genera from Oman, Omanodon and Shizarodon, also reveal a mix of similarities to both cheirogaleids and anchomomyin adapoids. Resolving the phylogenetic position of these Africa primates of the early Tertiary will surely require more and better fossils. By the early to middle Miocene, lorisoids were well established in East Africa, and the debate about whether these represent lorisines or galagines is reviewed. Neontological data are used to address the controversial branching sequences among extent lorisid clades. Data from the skin and scent glands, when integrated with other lines of evidence, suggest that Asian and African lorisines share a common lorisine ancestry. The hypothesis of an African clade containing both pottos and galagos to the exclusion of Asian lorisines is less tenable. True galagines are found in the fossil record of Namibia, while true lorisines are known from the Miocene of Asia. The hypothetical branching sequences can be integrated with behavioral and morphological features to develop an adaptive model of lorisoid divergence. By specializing on two different foraging modes early in their radiation, lorisines and galagines subsequently underwent a chain of integrated evolutionary changes eventually having an impact on many components of locomotor behavior, anatomy, physiology, reproduction, life history, and social behavior. Ongoing evolutionary studies of extant galagines are illuminating population phenomena and processes of speciation in an ecological context.

Africa↗

[[Child-sex effects on further births]].

This paper clarifies the child-sex effects on the number of additional children in Japan. The data were retrospective birth histories of the 8th Japanese National Fertility Survey carried out by the Institute of Population Problems in 1982. 1st, the authors found that the majority of the Japanese had a balanced sex preference. There was a slight shift from boy preference to girl preference in terms of the parity progression ratio. The effect of the 1st child's sex was small, but the effect of the parity-2 sex combination was as big or bigger than that of other socioeconomic variables. Next, the authors observed some evidence suggesting strong sex preference in opinion and behavior, such as differential intentions of further childbearing due to the sex of previous children and differences in the number of abortions caused by the sex combination of living children. Finally, the authors noted further issues to be examined in the study of sex preference in Japan.

Abortion, Induced↗