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Bendectin and human congenital malformations.

The relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations was prospectively studied in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). There were 58 categories of congenital malformations; three of them were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). This is exactly the number of associations that would be expected by chance. An independent study (the Collaborative Perinatal Project) was used to determine whether vomiting during pregnancy in the absence of Bendectin use was associated with these three malformations. Two of the three (microcephaly and cataract) had strong positive associations with vomiting in the absence of Bendectin use. We conclude that there is no increase in the overall rate of major malformations after exposure to Bendectin and that the three associations found between Bendectin and individual malformations are unlikely to be causal.

Abnormalities, Drug-Induced↗

Effects of early health-insurance programs on European mortality and fertility trends.

In this study, we examined the mortality and fertility effects of the early health-insurance programs sponsored by several European governments in the course of the demographic transition. Three sets of effects were hypothesized, and tested with data for five countries, covering the 1875-1913 period. First, although initially small, the growing health-insurance coverage of national populations accelerated longer-term downtrends in mortality. It not only expanded access to health care, but also helped in disseminating health information and awareness. Second, widening coverage also had an opposite effect on fertility; by lowering the costs of bearing and rearing children, it acted to slow the ongoing downtrend in marital fertility. Third, there was a diverse set of interactions between the mortality and fertility effects. Improved prospects for the survival of infants and children weakened parents' motivation to produce "extra" offspring to offset losses to mortality and to insure against future losses. Child survival was further enhanced by longer intervals between births and fewer children per family. However, the reduced cost of children tended to dilute these antenatal effects. Our regression results supported the expected pattern of partial effects, but simulations were needed to gauge the total impacts of health-insurance. Two sets of simulations were conducted: first, historical simulations, which closely tracked the actual experience of each sample country; second, counterfactuals, in which health-insurance coverage was set at zero for the entire time period. Comparisons of the historical and counterfactual simulations clearly indicated that health-insurance accelerated the downtrend in mortality, but slightly retarded the secular decline in marital fertility. These effects varied in magnitude, but not in direction, among the sample countries.

Birth Rate↗

Smoking and orofacial clefts: a United Kingdom-based case-control study.

OBJECTIVE: To investigate the association between smoking and orofacial clefts in the United Kingdom. DESIGN: Case-control study in which the mother's exposure to tobacco smoke was assessed by a structured interview. SETTING: Scotland and the Manchester and Merseyside regions of England. PARTICIPANTS: One hundred ninety children born with oral cleft between September 1, 1997, and January 31, 2000, and 248 population controls, matched with the cases on sex, date of birth, and region. MAIN OUTCOME MEASURE: Cleft lip with or without cleft palate and cleft palate. RESULTS: There was a positive association between maternal smoking during the first trimester of pregnancy and both cleft lip with or without cleft palate (odds ratio 1.9, 95% confidence interval 1.1 to 3.1) and cleft palate (odds ratio 2.3, 95% confidence interval 1.3 to 4.1). There was evidence of a dose-response relationship for both types of cleft. An effect of passive smoking could not be excluded in mothers who did not smoke themselves. CONCLUSION: The small increased risk for cleft lip with or without cleft palate in the offspring of women who smoke during pregnancy observed in this study is in line with previous evidence. In contrast to some previous studies, an increased risk was also apparent for cleft palate. In these U.K. data, there was evidence of a dose-response effect of maternal smoking for both types of cleft. The data were compatible with a modest effect of maternal passive smoking, but the study lacked statistical power to detect or exclude such an effect with confidence. It may be useful to incorporate information on the effects of maternal smoking on oral clefts into public health campaigns on the consequences of maternal smoking.

Case-Control Studies↗

Job stress and adverse outcome of pregnancy: a causal link or recall bias?

A case-base study in a population of 214,108 commercial and clerical female workers in Denmark during the period 1983-1985 investigated whether increasing job stress, defined as increasing job demands and decreasing job control, increased the risk of an adverse outcome of pregnancy. Information on the cohort, the outcome of 24,362 pregnancies, was obtained by linkage with nationwide health registers. Six case groups were selected: 1) 2,248 spontaneous abortions, 2) 209 stillbirths or deaths within the first year of life, 3) 661 infants with congenital malformations, 3) 593 preterm deliveries, 4) 587 infants with term low birth weights, 5) 988 infants with light-for-date birth weights, and 6) a random sample of 2,252 pregnancies that constituted the reference group. Information on exposure was obtained by mailed questionnaire. When dichotomized scales on data concerning job demand and control were used, there was an increased relative risk of spontaneous abortion (odds ratio = 1.28, 95% confidence interval (CI) 1.05-1.57) and term low birth weight (odds ratio = 1.46, 95% CI 1.05-2.04) for women experiencing high job stress. For the other case groups, the odds ratios were as follows: congenital malformation, 1.23 (95% CI 0.93-1.63); preterm delivery, 1.03 (95% CI 0.77-1.39); light-for-date birth weight, 1.08 (95% CI 0.83-1.40); and stillbirth/death within the first year of life, 1.42 (95% CI 0.90-2.24). No substantial response bias was found. When occupational titles were used as an exposure matrix, no increased risk was found, except for term low birth weight. Recall bias is one possible explanation. Thus, the results must be interpreted with caution.

Adolescent↗

Delayed excess mortality after exposure to measles during the first six months of life.

In an urban area of Guinea-Bissau, 71 children exposed to measles before age 6 months had a mortality risk of 34% (95% confidence interval (Cl) 24-47) between 6 and 60 months of age. The mortality risk for the 205 other children of the same birth cohort who had not been exposed to or developed measles was 11% (95% Cl 9-15), a significant difference compared with exposed children. With a version of the Cox regression model, maternal education was found to be the only background factor with a significant effect on mortality. When background factors were controlled for, the mortality of children exposed to measles was significantly higher than that of controls in each of the age intervals 6-11, 12-23, and 24-35 months. For the large subgroup of children of mothers without any formal education, exposed children had 5.7 times (95% Cl 2.7-12.0) higher mortality than did the control children in the age interval 6-35 months. Diarrhea deaths were particularly common among exposed children. Of 22 children who had been exposed before age 6 months during a subsequent epidemic and had a blood test taken, there was a significantly higher mortality risk (27%) between 6 months and 5 years than in the 26 controls who had a blood test (0%). Children who had elevated antibody titers to measles after exposure had a particularly high mortality compared with controls. These results suggest that later childhood mortality may be related to infectious experiences during the first months of life. The possible long-term health consequences of exposure to measles virus should be considered when assessing the value of measles control programs.

Child, Preschool↗

Effects of age, sex, and post mortem interval on intestinal lengths of horses during development.

Lengths of small intestine, caecum, ascending colon and descending colon were measured in intestinal tracts from 103 foetuses, foals and adult horses. Intestinal tracts from 21 of the horses were measured at varying intervals after death. Total intestinal length increased markedly from mid-gestation to one year of age, then showed little increment up to 35 years. Small intestinal length increased most rapidly in the first month of life. Caecal length increased most rapidly from one to six months and length of ascending colon increased most rapidly between one week and one year. Descending colon length increased gradually after birth. Periods of rapid increase in length of various intestinal segments and alterations in the percentage of total intestinal length were associated with periods of rapid body growth and changes in dietary composition. Sex and post mortem interval did not affect intestinal length significantly.

Animals↗

Reported multivitamin consumption and the occurrence of multiple congenital anomalies.

The purpose of this case-control study was to determine whether multivitamin use is associated with the occurrence of multiple congenital anomalies (MCA). MCA case-infants were infants with two or more major birth defects affecting at least two different organ systems, with no recognized chromosome abnormality or single gene disorder. Control-infants were a random sample of live births with no major birth defects from the same population (metropolitan Atlanta) and time period (1993-1997) as the case-infants. Exposure to multivitamins, cereals, and supplements was ascertained from a maternal telephone interview and classified based on folic acid content. We compared women who used multivitamins three or more times per week with women who were not exposed to vitamins/cereals/supplements during the periconceptional period (3 months before pregnancy through the first trimester), adjusting for maternal age, education, race/ethnicity, first degree family history of a major birth defect, pre-pregnancy maternal body mass index, gravidity, and first trimester alcohol use and cigarette smoking. Periconceptional multivitamin use was associated with MCA among all infants (adjusted odds ratio [aOR]=2.4, 95% confidence interval [CI] 0.9-6.7), and especially when analysis was limited to those with no family history of major defects (aOR=4.0, 95% CI 1.3-12.8). MCA-infants with urinary obstructive defects were more common among multivitamin-exposed infants than among unexposed infants, but this defect did not occur within a consistent pattern of defects. While these findings provide some support for one previous study, the interpretation remains unclear given the proven protective effect of multivitamins containing folic acid on isolated neural tube defects and possibly other types of defects.

Abnormalities, Drug-Induced↗

Population demography of Northern muriquis (Brachyteles hypoxanthus) at the Estação Biológica de Caratinga/Reserva particular do Patrimônio Natural-Felìciano Miguel Abdala, Minas Gerais, Brazil.

The 957-ha forest at the Estação Biológica de Caratinga/Reserva Particular do Patrimônio Natural-Felìciano Miguel Abdala, in Minas Gerais, Brazil, supports one of the largest known populations of the critically endangered northern muriqui (Brachyteles hypoxanthus). We combine long-term data on one group that has been monitored since 1982 with new data obtained on the other three groups since 2002 and 2003 to describe the demographic structure of this population, evaluate its potential for future growth, and predict how dispersal and competitive regimes may change in response to current demographic conditions. As of January 2005, the 226 individuals in the population were divided into four mixed-sex groups with 37-77 members, and an all-male unit whose eight males maintained transient associations with two of the mixed-sex groups. Although 51.77% of the population was female, the sex ratio among adults and subadults was female-biased (0.75), while that among immatures was male-biased (1.47). Consistent with expectations from mean interbirth intervals, 64.18% of adult females gave birth in 2003 and 2004. However, by January 2005, only 52.31% of adult females were still carrying infants <24 months of age due to unusually high infant mortality. First-year survivorship among the 25 infants born in the population in 2003 was only 76%, considerably lower than previously documented in the longest-studied group. High female fecundity is indicative of a healthy population, but the current male bias in births will result in a decline in the population growth rate within two decades, and may increase levels of male reproductive competition and alter dispersal patterns.

Age Distribution↗

Differences in twins: the importance of birth order.

Despite the clinical impression that firstborn twins do better than second-born twins, recent reports have shown no difference in perinatal mortality between them. In order to evaluate differences in twins, more sensitive means than perinatal deaths are necessary. This study examines differences between 80 firstborn and second-born twin pairs with respect to Apgar score, umbilical venous and arterial blood gas, and acid-base data. The umbilical venous and arterial blood PO2, PCO2, base deficit, pH, and lactic acid concentration were measured in paired samples and compared with the paired t test and chi 2 when applicable. Statistically significant differences favoring twin A, the firstborn, were found in 1-minute Apgar score, umbilical venous pH, PO2, and PCO2, and umbilical arterial PO2. The other factors in umbilical venous and arterial blood did not show statistically significant differences. When these parameters were examined with respect to route of delivery, monochorionic and dichorionic twins, interval between twins, and vertex twins only, with the possible effects of malpresentation eliminated, the results persistently favored the firstborn twin. Thus it is unequivocally demonstrated that there are substantial differences at birth favoring the first twin, despite similar perinatal mortality for both. The data suggest that the second-born twin has potentially greater susceptibility to hypoxia and trauma.

Apgar Score↗

Postnatal development of the vasopressinergic system in golden hamsters.

Adult golden hamsters, as compared to rats, lack several parvicellular vasopressinergic cell groups. We looked at the development of the vasopressinergic system in hamsters to draw comparisons with maturing rats. Arginine-vasopressin-immunoreactive (AVP-ir) neurons, their fibers and associated AVP binding sites were observed at several intervals after birth. Different rates of maturation were observed between different populations of vasopressinergic neurons. Within the suprachiasmatic nucleus (SCN), small AVP-ir neurons, their fibers and related binding sites maturated gradually during the first month after birth. In comparison, large AVP-ir neurons were apparent in newborn animals. Similarly, AVP-ir fibers and AVP binding sites were also present in the brain of newborns within areas not related to small vasopressinergic neurons from the SCN, such as the central amygdala (CeA) or the cerebral cortex. During the following weeks, a heterogenous pattern of development was observed within such areas. As the neurosecretory vasopressinergic system appeared to develop gradually, projections to the brain and their associated binding sites developed rapidly during the first week of life. Transient patterns of maturation were observed within certain sites. Indeed, some of the labelling observed in newborns regressed later. As similar reports were made in rats, our observations draw analogies between the vasopressinergic systems of these two species, beside their apparent dissimilarities in adult animals. Furthermore, our data also reinforce the concept that large vasopressinergic neurons do not constitute a homogenous population.

Aging↗

A longitudinal study of the physical growth of Japanese infants.

In order to clarify the characteristics of the physical growth of Japanese infants up to 1 year of age, the data of 3183 infants from 53 hospitals in Japan were collected. Percentile values were calculated from the measurement of body weight, recumbent length, and head circumference, with some additional data interpolated to fill the gaps in the measurements. Compared to the National Center for Health Statistics (NCHS) standard, the recumbent length and head circumference of these infants were smaller throughout the observation period, while body weight was larger at 0-6 months of age, and smaller at 8-12 months of age. The cases were divided into five groups according to birth weight, to examine the influence of foetal growth. The 50th percentile curves of each group were parallel and the intervals between the 3rd and 97th percentile curves in each group became wider in the first 6 months of life, up to the interval of 2.20-3.18 Kg. There was no significant difference in body weight among three groups according to feeding methods, in any age period.

Body Height↗

Heterogeneity of the effect of family history on breast cancer risk.

We studied the effects of family history on breast cancer risk among 2,908 cases and 3,180 controls, selected from participants in a nationwide screening project. First-degree family history was associated with a twofold risk increase. Second-degree family history effects were minimal, after adjusting for effects of first-degree relatives. Family history effects were not confounded by age at menarche, age at first full-term birth, age at natural menopause, or previous benign breast disease. Risks from mother's and sister's history were independent. The odds ratio (OR) from a maternal history, 1.9 (95% confidence interval [CI]: 1.6-2.3), varied little by the subject's age at diagnosis, menopause status, or disease laterality. Interactions of maternal history effects with multiple breast biopsies and age at menopause were greater than additive, indicating common mechanistic pathways. The OR from a sister's history was 2.3 (95% CI: 1.9-2.8) and was increased among women who were less than 45 (OR = 6.9), had bilateral disease (OR = 4.7), or were premenopausal (OR = 4.4). The effects from a mother's history and a sister's history are modified in different directions by different factors, providing further indication of the separate roles of a mother's and sister's history in breast cancer etiology.

Adult↗

Case-control study of risk factors for cervical squamous cell neoplasia in Denmark. IV: role of smoking habits.

The role of smoking and other risk factors for cervical neoplasia was investigated in a population-based case-control study of 586 women with histologically verified cervical squamous-cell carcinoma in situ (CIS), and 59 women with invasive squamous-cell cervical cancer from Copenhagen. Controls were randomly selected from the general female population using the computerized Danish Central Population Register. After adjustment for a variety of confounding variables, which were all significantly associated with CIS risk and included age, number of partners, proportion of sexually active life without barrier contraceptive use, years with intra-uterine devices, number of births, and age at first episode of genital warts (as a proxy measure for human papillomavirus exposure), current cigarette smoking was found to be significantly associated with CIS [adjusted relative risk (RR) = 2.4; 95% confidence interval (CI): 1.7-3.4]. Ex-smokers had a lower, but still significantly increased risk (RR = 1.6; 95% CI: 1.0-2.7). A dose-response relationship was present, especially for number of cigarettes smoked per day. In contrast, the crude estimates showed a weak association between invasive cervical cancer and smoking, which however disappeared after confounder control. The results of the present study support the hypothesis implicating smoking as a risk factor for CIS.

Adult↗

Immunologic consequences of feeding infants with cow milk and soy products.

Various products and regimens proposed for feeding infants when the mother's milk is not available have been evaluated intensively for capacity to achieve optimal nutrition. The immunologic consequences of feeding the foreign proteins contained in the various products have received much less attention and no systematic investigations have been done for comparable immunologic evaluation. Sera obtained at intervals from normal infants fed cow milk and soybean products from birth in different regimens were analyzed for antibodies to five major milk proteins and a soy protein isolate. Antibody levels increased slowly during the first 4 months, reaching a peak about 6 months of age. In infants fed cow milk products or a soy product from birth to 112 days of age and then given various cow milk products the following antibody responses were observed: The level of serum antibodies attained was highest with pasteurized cow milk and lower with heat-treated cow milk or a milk base formula of lower protein content. Feeding a soy product from birth for 112 days did not prevent a brisk antibody response to cow milk introduced subsequently, comparable to or greater than the antibody response seen when cow milk products were fed from birth. Clinically no immunologic disorders were detected in association with antibody responses to the various products and regimens. The implications of the findings for infant feeding and immunologic disorders are discussed.

Adolescent↗

Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia.

AIMS: To compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL). METHODS: Over a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL. RESULTS: The two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)). CONCLUSIONS: In the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.

Age of Onset↗

Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years.

Five retrospective studies have reported an association between antibiotic use in early life and asthma in childhood. We studied the relationship between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, and eczema at age 5 years among 448 children with a parental history of atopy monitored from birth. After adjustment for potential confounders, we found no significant association between antibiotic use in the first year of life and asthma (odds ratio [OR] for one versus no courses of antibiotics, 0.5; 95% confidence interval [CI] for OR, 0.2 to 1.5; OR for two or more versus no courses of antibiotics, 1.0; 95% CI for OR, 0.5 to 2.2), recurrent wheezing, allergic rhinitis, or eczema at age 5 years. There was no significant association between antibiotic use in the first year of life and having at least one of three atopic diseases (asthma, allergic rhinitis, or eczema) at age 5 years (OR for one versus no courses of antibiotics, 0.7; 95% CI, 0.4 to 1.4; OR for two or more versus no courses of antibiotics, 0.9; 95% CI, 0.5 to 1.4). Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood.

Administration, Oral↗

Fracture risk among First Nations people: a retrospective matched cohort study.

BACKGROUND: Canadian First Nations people have unique cultural, socioeconomic and health-related factors that may affect fracture rates. We sought to determine the overall and site-specific fracture rates of First Nations people compared with non-First Nations people. METHODS: We studied fracture rates among First Nations people aged 20 years and older (n = 32 692) using the Manitoba administrative health database (1987-1999). We used federal and provincial sources to identify ethnicity, and we randomly matched each First Nations person with 3 people of the same sex and year of birth who did not meet this definition of First Nations ethnicity (n = 98 076). We used a provincial database of hospital separations and physician billing claims to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for each fracture type based on a 5-year age strata. RESULTS: First Nations people had significantly higher rates of any fracture (age- and sex-adjusted SIR 2.23, 95% CI 2.18-2.29). Hip fractures (SIR 1.88, 95% CI 1.61-2.14), wrist fractures (SIR 3.01, 95% CI 2.63-3.42) and spine fractures (SIR 1.93, 95% CI 1.79-2.20) occurred predominantly in older people and women. In contrast, craniofacial fractures (SIR 5.07, 95% CI 4.74-5.42) were predominant in men and younger adults. INTERPRETATION: First Nations people are a previously unidentified group at high risk for fracture.

Adult↗

Relative efficiencies of wither height and body weight increase from birth until first calving in Holstein cattle.

Female Holstein calves from the Purina Research Center herd averaged 74 cm of height at withers and 40 kg of body weight (BW) at birth. At first calving (24 mo of age), calves averaged 138 cm of height at withers, 611 kg at precalving BW, and 547 kg at postcalving BW. Fifty percent of the total height increase occurred from birth to 6 mo of age, 25% occurred during 7 to 12 mo of age, and 25% occurred during 13 to 24 mo of age. Twenty-five percent of the total BW increase occurred from birth to 6 mo of age, 25% occurred from 6 to 12 mo of age, and the remaining 50% occurred from 13 to 24 mo of age. The increase in BW for 2-mo intervals, expressed as a proportion of the BW of the previous 2-mo interval, declined most rapidly during the first 6 mo, intermediately during the second 6 mo, and more slowly and progressively during the final 12 mo. Feed cost per unit of BW gain was lowest during the first 6 mo and then increased at a decreasing rate over the final 18 mo. The proportion of BW to height linearly increased over the 24-mo period. The increase in wither height as a proportion of the wither height during the previous period was greatest during the first 6 mo, intermediate during the second 6 mo, and lowest in the final 12 mo. Feed cost per unit of height increase was lowest in the first 6 mo, intermediate during the second 6 mo, and highest with a rapid increase during the final 12 mo. The increases in relative BW and wither height are the most rapid and cost efficient during the first 6 mo of life.

Aging↗