Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.birth weight, small for gestational age and preterm births), in a two-level hierarchical model.A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes  and area-based (median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.Overall, the findings of the study suggested greater likelihood of  Adverse birth outcomes such as low birth weight and its determinants, preterm births and intrauterine growth retardation have been associated with indicators of socioeconomic status and physical environment -3. The iSocioeconomic status is a determinant of health in populations ,12, and The present study was carried out to identify and explain disparities in reduced birth weight and preterm births in seven counties of Eastern Massachusetts between 1996 and 2002. We intended in this study to explain the variation in birth outcomes as a function of the individual and area-based level SEM, measures of traffic and land use as indices of physical environment, and their interaction using a two-level hierarchical model. We also sought to assess the degree of confounding of one group of factors by the other likely to be present in previous reports that have not examined these two groups of factors together.all singleton live births in Eastern Massachusetts for the counties of Bristol, Essex, Middlesex, Norfolk, Plymouth, Suffolk, and Worcester obtained from the Massachusetts Birth Registry for the period between January 1, 1996 and December 31, 2002. The population of the seven counties covered about 83 percent of the state's population. Individual address of mother at time of birth was geocoded by a private firm by matching the address to state, city ZIPcode and TIGER street network data, and assigning to this street address latitude and longitude coordinates. The geocoding was then reassessed by us for accuracy and completeness. The study and the use of birth data was approved by the Massachusetts Department of Public Health and the Human Subjects Committee of the Harvard School of Public Health. We restricted our study to births born between 20 and 45 weeks of gestation, with birth weight between 500 and 5500 grams. We also excluded those births that could not be correctly assigned an address (4.9 percent), resulting in the final number used for the study of 425 751.The study population included birth weight (continuous variable), small for gestational age (SGA) and preterm births (dichotomous variables). Low birth weight among term newborns (born at ≥ 37 to 45 weeks of gestation) may represent intrauterine growth retardation. We constructed a measure of intrauterine growth retardation, SGA, by calculating the lowest 10 percentile of the distribution of weight by gestational week, maternal race, and infant gender among all term births as the cutoff. We assigned 1 to those births falling below this cutoff and 0 otherwise (reference group). Preterm births were defined as all neonates born between 20 and <37 weeks of gestation. The reference group for preterm births was defined as all term births , which conducts annual traffic data collection. This dataset included average daily traffic (ADT) as an attribute.A grid made up of points spaced 200 meters apart was created over the study area of Eastern Massachusetts, using ArcGIS 9.1  buffer tool. Around each grid point we created 100 meters radius circles. We intersected these circles with the MHD 2002 roads to create a combined dataset of roads within each circle. Cumulative ADT (CADT) was calculated for all road segments within 100 meters around each grid point as: CADT = Σ  . GeocodeProtected and recreational open space was downloaded from MassGIS, Massachusetts Executive Office of Environmental Affairs . The subWe obtained from the birth registry information on mother's race, years of education, and the Kotelchuck index of adequacy of prenatal care utilization (APNCU). Race/ethnic background of mother was categorized as: White, African-American, Asian, and Hispanic. Due to small numbers we excluded births from Native American mothers from the analyses .high school or less ; some college (13–15 years); and college or postgraduate (≥ 16 years). We categorized the APNCU, a measure based on the number and the time of start of mother's prenatal visits [inadequate (<50 percent of expected visits used); intermediate (50–79 percent); appropriate (80–109 percent); and appropriate plus (≥ 110 percent). Adequacy of prenatal care can be a predictor of accessibility of mother to health care, and inability to have appropriate prenatal care is more likely for those living in poorer neighborhoods.We categorized education as: l visits , into: iWe obtained data from the United States Census Bureau of 2000 on median household income for each census tract in the study area, and assigned these to births whose address belonged to that tract. Preliminary analyses controlled for several other variables at the census tract level: percent below poverty, percent with low education, percent of ethnic background  and found no association or confounding by these factors, therefore not presented in this work.Measures of traffic were log transformed to stabilize the variance and used as such in the analyses. We controlled additionally in the models for age of mother, gestational age, amount of cigarettes smoked during pregnancy, chronic conditions of mother or conditions of pregnancy , if the mother ever had a previous preterm birth, if the mother ever had a previous infant weighting 4000 grams or more, gender of infant, and year of birth to control for time trends.Smoking during pregnancy is associated with adverse births, and it has not been controlled for in many previous studies. Because smoking varies with social class in the United States , it may ij be the response (birth weight) in the ith subject in census tract j, and child sexi, maternal agei, traffic at individual address of motheri, individual-level socioeconomic measures (ILSEM)i, census tract-level socioeconomic measures (TLSEM)j denote the set of covariates of interest. Then we considered models of the formFor continuous outcomes such as birth weight, linear mixed regression models were carried out . For exaeij is the error term, and uj is the tract-specific random intercept and represents the variation of the rate in the groups due to unmeasured factors. This intercept is randomly generated from a normal distribution as suggested by Pickle [Here y Pickle , modeledSGA and preterm births, Yij will be the outcome in the ith subject in the jth census tract, with the model of the formBinomial data was modeled similarly to the normal data. For uj is a random census tract intercept. This approach was implemented using a recent version of the SAS procedure GLIMMIX [where  GLIMMIX .ui would exhibit spatial correlation, from either the models for Gaussian or Binomial data. We modeled this spatial correlation by assigning the latitude and longitude of the population centroid of each census tract to each observation in the group i, and fitting an exponential spatial correlation structure.It was likely that the We examined effect modification by median household income and maternal education for the association between birth weight and traffic and land use variables. We assessed precision in the difference of effects by calculating 95 percent confidence intervals around that difference .mean birth weight and the percentages of SGA, preterm births and a comparison group by categories of socio-demographic variables  compared births from mothers with >12 years of educational attainment. The prevalences of mothers with high school or less educational attainment with SGA and preterm births were about one third greater than that of the comparison group (31 percent and 26 percent greater respectively).more than appropriate prenatal care, twice as much as the comparison group, a suggestion of at risk pregnancies. About 9 percent of mothers had reported or were diagnosed with chronic diseases or conditions of pregnancy  – 41 percent of these had sought appropriate prenatal care and 48 percent more than appropriate prenatal care.Birth weight was lower among mothers who had received less than appropriate prenatal care. The prevalence of mothers who had received inadequate prenatal care was greater for SGA and preterm births than for comparison group. However, 76.5 percent of mothers who had preterm births had received Younger mothers (<20 years old) had on average newborns of lower birth weight compared to births from older age groups; they were more likely to have SGA or preterm births than the comparison group (5.2 percent and 4 percent respectively). Worse birth outcomes were observed for mothers with a history of smoking during or pre-pregnancy, and among those with a previous preterm birth, although the numbers for this last one were small. Gender of infant did not make any difference on birth outcome.We calculated mean birth weight and percent of SGA, preterm birth and comparison group by quartiles of traffic and land use variables and median household income table . All advWe estimated the covariate adjusted associations between individual and census tract level SEM : -12.9 g, -4.3 g). In contrast, being born from mothers with college and postgraduate education (≥ 16 years) was associated with a greater birth weight . Mothers with ≤ 12 year of educational attainment were similarly at greater risk of SGA and preterm births  = 1.06; 95 percent CI: 1.00 1.11). No increased risk was seen for Hispanic mothers, while a protective effect was seen for Asian mothers .more than appropriate prenatal care. In this case, it is important to note that more than appropriate prenatal care is usually provided to mothers at risk of pregnancy complications, therefore at greater risk of poor birth outcomes. Excess risks of SGA and preterm birth were seen amongst mothers who had been provided inadequate or intermediate prenatal care. The risk for preterm birth was more than four-fold if received inadequate care; however, a 9-fold risk of preterm births was associated with receiving more than appropriate prenatal care, which as noted above suggests pregnancies at risk.Lower birth weight was observed among newborns from mothers who had been provided with less than appropriate prenatal care , when compared to mothers who had appropriate prenatal care. A similar finding, but with a weaker effect  was observed for mothers who had Controlling for individual SEM , census tract level median household income was positively associated with birth weight , inversely related to risk of SGA , but not associated with risk of preterm birth  table .When race and maternal education were excluded from the SEM model, the effect of median household income on birth weight increased to 22.4 g , and if race but not maternal education were included, the effect of median household income was 9.4 g . Hence, the effect of median household income was reduced by 61 percent after controlling for individual SEM covariates.The results for measures of traffic are presented for one standard deviation (SD) change in the distribution of the log-transformed variable, and for land use for 1 SD change in the variable distribution table . The meaInclusion in models of traffic and land use variables did not affect the coefficients for educational attainment, or the coefficients for race and the index of prenatal care for birth weight . When race but not educational attainment, APNCU or the indicator of median household income were included in the model that effect was reduced to 4.3 g , while the effect from the model with educational attainment, APNCU and median household income , but not race was not very different from that of model without any of the SEM variables. The effect of land use on birth weight was also reduced in the full model , and the effect of cumulative traffic density became imprecise. The risk of SGA associated with cumulative traffic density did not change in the full model, while the protective effects of distance to roads and percent open space weakened.There was no important difference observed for the effect of cumulative traffic density on birth weight by educational attainment table . We obseWe also examined three way interactions between maternal education, median household income by tract, and our measures of physical environment and found no important differences (data not shown).First, we used a two-level hierarchical model to estimate the variability in birth outcomes due to individual and contextual level SEM and indices of physical environment. A number of epidemiologic studies from the US and other countries have shown associations between air pollution and birth weight and preterm births, in particular with carbon monoxide and particulate matter [We examined the effects of social and physical environment on birth outcomes in a study of singleton births in Eastern Massachusetts, North East US, between 1996 and 2002. Two key components of this study are worth mentioning. e matter ,24,39-41e matter ,40,42. He matter ,24. In We matter , individe matter . In a hiUsing the two-level hierarchical model, we found effects of individual and contextual level SEM for all three outcomes in the study ; the effects of traffic and land use variables were mainly seen with birth weight, with the exception of an effect of cumulative traffic density on SGA. We found that mothers with lower educational attainment were more likely of adverse births than mothers who had higher education. Lower birth weight was seen among African-American, Asian and Hispanic mothers when compared to births from White mothers; risk of preterm birth was greater for mothers of African-American background than for any other ethnic group. Having had less than appropriate prenatal care also increased the risk of adverse birth outcomes. None of the effects of individual SEM were affected when controlling for the contextual level SEM or indices of physical environment. Mothers from neighborhoods with lower median household income were also at greater risk of adverse birth outcomes. Measures of traffic exposure, estimated at the residential address of mother at time of birth, were associated with lower birth weight, and for cumulative traffic density with SGA, after control for both individual and area-based SEM.race/ethnicity of mother in SEM model reduced the effect of median household income on birth weight by 58 percent. Including just race/ethnicity in exposure model reduced the effect on birth weight of cumulative traffic density by 62 percent, distance to major roads by 25 percent, and that of land use as open space by 47 percent. These results suggest that race/ethnicity of mother is a strong confounder in this study. Racial/ethnic inequalities do predict health disparities, and such inequalities are a representation of a history of racial discrimination, economic deprivation, and the greater likelihood of adverse exposures throughout life [The two-level modeling approach enabled us to control for confounding of one factor by the other: individual and contextual SEM, and physical environment. While the effect for educational attainment, race and index of adequacy of prenatal care on birth weight did not change after controlling for indicators of physical environment (traffic and land use), the coefficient for median household income was reduced by 23 percent. We also saw a reduction in the effects of traffic and land use variables on birth weight after controlling for SEM. The presence of out life ,44. The out life .second key component in our study: cumulative traffic density and distance to major highways within a radius of the subjects' home. Distance to roadways has been reported to approximate somewhat better personal exposure levels of air pollutants than ambient measurements. Studies have reported strong gradients of pollutant concentrations and particle size distribution for distances beyond 100 meters from the roads [The precision of the observed relationship between air pollution and adverse birth outcomes in other studies has been largely affected by the measure of exposure assigned to each individual in the study. The majority of the studies that examined this relationship have not taken into account variation in pollution exposure within small localities, which can lead to exposure misclassification and distortion of the association. Two studies in California, US, merely averaged monitors within few miles of the residence of the child, for example ,30; a sthe roads ,47. In oThe geographic differences in the distribution of air pollutants are related to the geographic distribution of wealth and socioeconomic status ,48,49. HThere are limitations to this study that need to be mentioned. Exposure was estimated by distance to major highways and cumulative traffic density at individual birth addresses, as an approximate measure to concentrations of air pollutants. These exposure measures were, however, not directly related to personal air pollutant concentrations of each study subject. Also, mother address at time of birth was used to assign individual exposure indices. That address was not necessarily the address of mother during pregnancy, and we had no information available to correct for this. Both these limitations do introduce misclassification, and due to the non-selective nature of this error we would expect our study estimates to be underestimated. We had self-reported information on smoking during and before pregnancy which we used in this study to control for potential confounding by smoking. Because of the imprecision of the self-reported measure of this factor, one can argue that there may be residual confounding biasing the study estimates. However, in this study we controlled for a number of SEM and since smoking is strongly correlated with social class, residual confounding by smoking is expected to be small.In conclusion, the study offers a way to look at adverse health in two perspectives simultaneously: the physical and social environment. By using a broader view in trying to understand the mechanisms that determine population health, as the example in this study, one can contribute to improving epidemiologic research and hope to contribute in reducing health disparities in populations.ADT: average daily traffic; APNCU: adequacy of prenatal care utilization; CADT: cumulative average daily traffic; MHD: Massachusetts Highway Department; SEM: measures of socioeconomic status; SGA: small for gestational age; PT: preterm; TIGER: Topologically Integrated Geographic Encoding and Reference SystemsThe authors declare that they have no competing interests.All authors have made substantial contribution to this work. AZ and JS coordinated the study. AZ analyzed the data and drafted this manuscript. SJM participated with geocoding and exposure estimation for this work. AZ and JS are the guarantors for the results and interpretation of the study findings.


The aim was to study, in a population-based cohort design, whether first-born sons run a higher risk of testicular cancer than later born sons; to investigate whether this difference in risk was affected by birth cohort, age of the son, maternal age, interval to previous delivery and other reproductive factors; and, finally, to evaluate to what extent changes in women's parity over time might explain the increasing incidence of testicular cancer. By using data from the Civil Registration System, a database was established of all women born in Denmark since 1935 and all their children alive in 1968 or born later. Sons with testicular cancer were identified in the Danish Cancer Registry. Among 1015994 sons followed for 15981 967 person-years, 626 developed testicular cancer . Later born sons had a decreased risk of testicular cancer  compared with first-born sons. The RR was 0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for seminomas. There was no association between testicular cancer risk and overall parity of the mother, maternal or paternal age at the birth of the son, or maternal age at first birth. The decreased risk of testicular cancer among later born sons was not modified by age, birth cohort, interval to the previous birth, sex of the first-born child, or maternal age at birth of the son or at first birth. The increased proportion of first-borns from birth cohort 1946 to birth cohort 1969 only explained around 3% of an approximated two-fold increase in incidence between the cohorts. Our data document a distinctly higher risk of testicular cancer in first-born compared with later born sons and suggest that the most likely explanation should be sought among exposures in utero. The increase in the proportion of first-borns in the population has only contributed marginally to the increase in testicular cancer incidence.


This population-based cohort showed that being born into a larger family or to a mother with a history of miscarriage may increase childhood brain tumour risk.Using population-based linked birth and cancer registry data, we investigated whether the risk of brain tumour in childhood ( An increase in the incidence of central nervous system tumours has been observed during recent decades in a number of countries ; gestational age (to the nearest complete week); the number of previous pregnancies, live births, and miscarriages; mother's and father's year of birth; social class (based on father's occupation); method of infant feeding on discharge from the place of confinement; the number of persons aged above and below 15 years per household at the time of birth of the index child; and the number of living rooms and bedrooms in the household at the time of the birth. Maternal age at delivery, birth weight, and gestational age were taken directly from birth notification forms completed in obstetric units. The other information was collected by health visitors in the home typically within 1–2 weeks of birth. Details of incident cases of brain tumour in Northern Ireland between 1975 and 1997 were obtained from the Northern Ireland Cancer Registry. Using sex, surname, and date of birth, cases born in Northern Ireland between 1971 and 1986 were identified within the Child Health System database.χ2 test. All statistical analyses were performed using SAS® (version 8.2) and two-sided P-values are reported. Ethical approval was obtained from the Research Ethics Committee of the Queen's University of Belfast.As we did not actively follow-up the cohort for migration or death, we did not feel justified in calculating person-years of risk and modelling the risk of disease using Poisson or Cox regression. Instead, we approximated relative risks by calculating the odds ratios obtained from unconditional logistic regression models, an approximation that is reasonable for a rare disease such as brain tumour. Perinatal information about the children who subsequently developed a brain tumour was compared with children who did not develop a brain tumour using a n=9235), or with Down's syndrome (n=440) were excluded. The Northern Ireland Cancer Registry contains 251 patients diagnosed with brain tumours in Northern Ireland who were born between 1971 and 1986; of whom, 208 (82.9%) were identified within the Child Health System; 155 cases were malignant. The characteristics of the identified cases (n=155) and non-cases (n=420 436) are shown in The Child Health System contained data on 444 168 live births delivered between January 1971 and December 1986 in Northern Ireland. The Registrar General's Office, which registers all births within Northern Ireland, registered 444 111 live births for the same period. Only live births were included in this analysis. Newborns with congenital malformations (8883), missing birth weight or gestation age (4923), who were part of a twin or multiple gestations (This study indicates that a greater number of children (⩾3) and adults (⩾3) in the house at the time of delivery were associated with increased brain cancer risk.Boys more than girls were at an increased risk of brain tumours, a finding that has been previously reported for both lymphomas and leukaemias ; the undThe positive association between the number of children and adults in the household and brain cancer risk suggests that earlier exposure to infections in childhood may increase risk, perhaps due to immune modulation. In our study, there was no association between infant feeding practise and brain tumour risk. However, a recent study of brain tumour risk in relation to various indicators of infection during gestation and childhood highlighted two possible contradictory theories  babies were at an increased risk as compared with those of normal weight. To date, findings on birth weight and brain tumour risk have been inconsistent, although an association has been shown for high birth weight and astrocytoma risk  factors may be largely discounted.The study has some potential limitations. The relatively small number of cases precludes potentially important subgroup analyses. Data were collected by many observers and, although attempts were made to standardise procedures, variation in recording is likely to have occurred. However, such misclassification bias will result in an attenuation of real associations. The matching process will not have identified brain tumour cases born outside marriage, if they had a subsequent name change. As unmarried mothers are more likely to be younger and live with relatives (higher household densities) than their married counterparts, failure to identify these cases may have reduced the power of the study to detect associations between household densities, or young maternal age, and brain tumour risk. However, as birth records were identified for almost 83% of possible cases, this is not a major issue.in utero and during early childhood.This population-based study is the first cohort study to demonstrate that being born to a mother with a history of miscarriage or into a larger family may be a risk factor for brain tumours. Further investigation of this hypothesis is warranted, including the examination of infections that are likely to be transmitted placentally


A 55-year-old woman presented with 1 month history of right hypochondrium pain, vomiting, and jaundice. On examination, she had tender right hypochondrium and palpable gall bladder. Blood investigations revealed increased white cell count with eosinophilia; serum bilirubin (6 mg/dL) and alkaline phosphatase (900U/L) were raised; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were not significantly elevated. Ultrasonography showed a cyst in the right lobe of liver and dilated common bile duct (CBD) filled with echogenic debris. Gall bladder was distended and transonic. MRCP was performed for further evaluation. Cholangiographic thick slab MRCP revealed a cyst in the right lobe of liver closely related to right lobe ducts, with intracystic linear and irregular hypointensities; intrahepatic bile ducts were dilated and CBD filled with long, low signal intensity mass like structure. GB was distended and pancreatic duct slightly dilated .What is the diagnosis?Transverse and coronal plane heavily T2 weighted, thin slice MR images revealed the diagnosis. T2W axial and coronal MR images depicted a cyst in the right lobe with a focal beak like projection from the medial wall of the cyst extending toward and communicating with the right posterior sectoral duct; the cyst had a smooth thin wall and internal membranes Figures . These fIntrabiliary rupture of hydatid cyst is an imaging diagnosis. Following imaging findings have been described as suggestive of rupture of hydatid cyst into the biliary tract.2Cyst in the liver showing some irregularity of the wall, and hydatid sand, membranes and scolices inside.Communication between the liver cyst and dilated bile duct proximal to porta hepatis seen as focal discontinuity of the cyst wall.Dilated bile duct containing ruptured cyst membranes.Low signal intensity contents within the dilated CBD on MRCP may be due to sludge, pus, parasites, and calculi. However, demonstration of communication of such a dilated duct with a cyst, showing crumpled membranes, at or above the porta hepatis is highly suggestive of intrabiliary rupture of hydatid cyst and is the only direct sign of rupture. MRI usin2MRCP readily estabilishes the preoperative diagnosis of intrabiliary rupture of the hydatid cyst of liver, which is essential for its prompt management. ERCP may be employed for the removal of membranes from CBD and cyst drainage; this may be followed by operation for suturing the bile leakage without CBD exploration. Primary


Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.Body composition and metabolic risk were assessed in 2,249 men, aged 17–19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score  but showed greater weight gain during infancy  and had greater mean height  and weight  at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors. The metabolic syndrome is a key factor contributing to morbidity and mortality worldwide, both in industrialised populations and those passing through the nutritional transition However, not all risk factors for obesity are readily modifiable. Dietary energy density is an example of a modifiable determinant, as a propensity to consume energy-dense foods, associated with weight gain In this context is it valuable to investigate life history variables. Many life history traits such as age at maturation and adult size are related to early growth patterns in-utero growth of first-born babies may be restrained as they have lower birth weight and accelerated post-natal catch-up growth Recent work has suggested that birth order may be a non-modifiable risk factor for obesity. Current evidence suggests that first-born infants grow faster than later-born infantsIdentification of the effect of birth order on metabolic risk is important in relation to demographic trends, such as the restrictive family planning policies (one child policy) adopted in some nations and the worldwide decline in fertility Here we investigate the associations of birth-order with metabolic phenotype in early adulthood using data from a birth cohort of Brazilian young men. We tested two hypotheses. First, we wanted to confirm that first-born status was associated with low birth weight and faster infant growth. Second, we tested the hypothesis that metabolic risk was increased in first-borns compared to later-borns.During 1982, the three maternity hospitals in Pelotas, a southern Brazilian city, were visited daily and the 5914 live born infants whose family lived in the urban area of the city were weighed and their mothers interviewed. These children have been followed up on a number of occasions Socio-demographic and lifestyle information were collected, including: 1) schooling ; 2) social status ; 3) smoking history ; 4) birth order rank ; and 5) regular physical activity . Information was also collected in the early cohort visits on family income, maternal schooling, household wealth score and maternal smoking status during pregnancy, duration of breastfeeding.2)/impedance) to calculate fat-free mass  and hence fat mass (FM) as the difference from weight. Body mass index (BMI) was calculated and subjects categorised into three weight categories based on WHO cut-off scores including: normal weight (18.5<BMI<25 kg/m2), overweight (25≤BMI<30 kg/m2) and obese (BMI≥30 kg/m2). Body composition data were adjusted for height to calculate the fat mass index (FMI (kg/m2) = FM divided by height2) and fat free mass index (FFMI (kg/m2) = FFM divided by height2)Standing height was measured by a CMS stadiometer to the nearest mm with subjects barefood. Subjects were weighed in minimal clothing using a Tanita Body Fat Analyser scale , which also provided information on body composition through bio-electrical impedance. A validation sub-study was conducted in sample of 48 participants in the age range of the study cohort using total body water through deuterium dilution as the gold standard. We used the resulting validation equation + test was used for the categorical variables. The sample size was sufficient to detect a difference between birth order groups of 0.15 z-scores.Continuous variables were described using summary statistics. Student's t-test for independent samples was used to detect differences between subjects categorised according to birth order (first-born versus later-born). The chi square . First-borns also showed faster weight gains during infancy  and had greater mean height  and weight  at 43 months (data not shown). This greater weight and height tracked into early adulthood, with first-borns being significantly taller and heavier than later-borns. Although BMI was not related to birth order, first-borns had a significantly higher adiposity (FM) compared to later-borns Table 1.. The adjusted regression analysis showed the independent effect of birth order on body composition and metabolic risk. First-borns had higher body weight , FMI , FFMI ,fat mass/fat free mass ratio , BMI , triglycerides , and metabolic risk z-score  compared to later-borns .The relationship between first-born status and metabolic risk found in this study is likely to be mediated by early growth patterns. Ong et al.The lower birth weight of first-borns can be attributed to materno-fetal physiological interactions. Following implantation, cells from the outer layer of the blastocyst, known as trophoblast, invade the maternal endometrium and alter the structure of the arteries that transfer blood to the placentaOur findings contribute to understanding of the early origins of adult disease. Our data show that a demographic factor relevant to all human populations can generate variability in both early growth and later metabolic risk. These findings also have important implications for understanding the increasing prevalence of the metabolic syndrome worldwide, where many populations are undergoing demographic change in response to economic development. Globally, there is a trend towards lower fertility rate, such that increasing proportion of individuals will be first-borns. In Brazil, for example, the average number of children per women  dropped from 6.0 in 1960 to 1.8 currently.Between- and within-country comparisons of trends in the prevalence of the metabolic syndrome may incorrectly attribute birth order effects to environmental factors. This has implications for monitoring the efficacy of public health campaigns aimed at reducing the prevalence of degenerative diseases, and also for the projection of future treatment costs. The public health implication of our findings is that the increased metabolic risk of first-borns is likely to derive from an interaction between their lower birth weight and conditions favouring rapid post-natal growth. Our findings therefore have implications for the optimal nutritional management of individual infants.However, a number of questions still merit attention. For example, studies should describe in more detail the growth patterns that appear to lead to elevate metabolic risk, and identify the optimal time periods for intervention. Studies should also clarify the relative contribution of different possible underlying mechanisms  to the effects that we observed in these samples. Third, more research is required to establish the magnitude of the effect, whether it is similar in men and women, and whether it amplifies with age, as adverse metabolic profile consolidates. In these samples of young adults, the magnitude of the effect was relatively small, but degenerative diseases are expressed primarily from middle age and early-life effects tend to become more important through adulthood.


Susceptibility to atopy originates from effects of the environment on genes. Birth order has been identified as a risk factor for atopy and evidence for some candidate genes has been accumulated; however no study has yet assessed a birth order-gene interaction.IL13 polymorphisms with birth order on allergic sensitization at ages 4, 10 and 18 years.To investigate the interaction of IL13 were collected. Three SNPs were selected from IL13: rs20541 , rs1800925 (promoter region) and rs2066960 (intron 1). Analysis included multivariable log-linear regression analyses using repeated measurements to estimate prevalence ratios (PRs).Mother-infant dyads were recruited antenatally and followed prospectively to age 18 years. Questionnaire data ; skin prick test (SPT) at ages 4, 10, 18; total serum IgE and specific inhalant screen at age 10; and genotyping for IL13 on SPT was restricted only to first-born children . Similar findings were noted for firstborns regarding elevated total serum IgE at age 10  and specific inhalant screen .Of the 1456 participants, birth order information was available for 83.2% (1212/1456); SPT was performed on 67.4% at age 4, 71.2% at age 10 and 58.0% at age 18. The prevalence of atopy  increased from 19.7% at age 4, to 26.7% at 10 and 41.1% at age 18. Repeated measurement analysis indicated interaction between rs20541 and birth order on SPT. The stratified analyses demonstrated that the effect of IL13 polymorphisms on allergic sensitization. Future functional genetic research need to determine whether or not birth order is related to altered expression and methylation of the IL13 gene.This is the first study to show an interaction between birth order and  Atopy has been defined as the propensity of an individual to produce IgE in response to allergen and a predisposition to the development of allergic diseases, such as asthma, atopic dermatitis, food allergy or hay fever. It is defined operationally by elevations in serum levels of immunoglobulin E (IgE) reactive with allergens or skin test reactivity to allergens . Thus atThe documented increase in childhood asthma and other atopic disorders over the past three decades has necessitated a search for possible underlying mechanisms and mediators ,4. GenetPrevious studies have assessed two related ideas - the hygiene hypothesis and the birth order effect . The hygIn utero sensitization as a possible mechanism of modification of gene effects has been proposed, where birth order, as an indicator of variations in prenatal exposure, acts independent of the number of siblings [in utero exposure as indicated by changes in maternal IgE [intra uterine immune adaptation as a possible underlying mechanism.Other studies suggest that birth order may act through a different mechanism . In utersiblings ,11. A prsiblings  suggesternal IgE . If a prrnal IgE  suggestiIL13 polymorphisms [IL13 polymorphisms on childhood atopy.In a recent review, Vercelli  suggesteorphisms -21 on alin utero [In previous reports by our group and other researchers, birth order has been repeatedly found to be associated with atopic markers. For instance, we found that cord serum IgE was reduced in offspring with higher order, indicating that the sibling effect may have its origin in utero , before in utero , which sa priori hypothesis was that the birth order effect may interact with the genetic predisposition of the offspring in influencing future atopic manifestations. In order to test this hypothesis, we chose one of the most-studied "atopy genes," IL13. This choice seems appropriate because, if a gene-by-birth order interaction exists, it would be best demonstrated with a known gene. Finding such an interaction with a novel gene that does not have the kind of consistent replication so far demonstrated for IL13 may not be as scientifically robust.Our IL13 gene with prenatal factors.This report will be the first study to investigate the interaction between these important risk factors during early childhood, as well as sustained effects in adolescence, testing both the main effects and the interaction effects of the The study participants were mother-infant pairs enrolled in the 1989 Isle of Wight birth cohort study. This study represents an unselected whole population birth cohort based on the Isle of Wight, U.K. The Isle of Wight is an island (13 × 23 miles) just off the South Coast of England with a resident population of 130,000. The population is stable to the extent that the majority of participants in the cohort has not moved away and was thus available for follow up. This makes the island particularly attractive for long-term prospective epidemiological studies.Between January 1989 and February 1990, children born on the Isle of Wight, U.K. were recruited to participate in a longitudinal study . The local Research Ethics Committee approved the study and informed written parental consent was obtained for all the participants at recruitment and subsequently at each follow up. This whole-population birth cohort was largely Caucasian (99%) and was living in a semi-rural, non-farming environment with no heavy industry.The Isle of Wight birth cohort has been described in detail elsewhere ,24. BrieIL13 SNPs and birth order on atopic outcomes. Thus, the main exposure variables involved in the interaction terms were IL13 polymorphisms and birth order. Outcome variables include skin prick tests at ages 4, 10, and 18, total IgE at birth (cord serum) and at age 10, and inhalant IgE screen at age 10. The potential confounders we adjusted for were gender, environmental tobacco smoke exposure, family SES cluster, and gestational age. Gender was classified into male and female while gestational age was assessed in weeks. Other variables are described in greater detail below.This is a population-based association study that tests the interaction effects between IL13 gene were examined using the SNPper and Applied Biosystems databases. Genotyping was conducted by fluorogenic 5' nuclease chemistry PCR using Assays on Demand kits cycled on a 7900HT Sequence Detection System , or biotin-streptavidin-based pyrosequencing performed on PSQ-96 instrumentation .Genomic DNA was isolated from blood samples using QIAamp DNA Blood Kits  or the ABI PRISM™ 6100 Nucleic Acid PrepStation . Polymorphisms in the IL13 is a small gene (2.9 kb) characterized by extensive linkage disequilibrium, thus genotyping a few polymorphisms provided adequate assessment of genetic associations. Five IL13 SNPs were genotyped , 10 (n = 1036) and 18 years (n = 845) using a standard battery of food and aeroallergens , which have been previously described . After 1®  [®  designed to measure IgE between 2.0 to 1000 kU/L. For our analysis, maternal IgE was dichotomized into < 100 and ≥ 100 kU/L.Total IgE was measured in samples of cord serum n = 1340) and serum collected at age 10 (n = 923). Total IgE in cord serum was measured using Pharmacia IgE EIA Sweden) , which i0 and ser Sweden) . MaternaUsing information from questionnaires on maternal atopic history  and data from the measured maternal IgE level at birth (n = 1037), we created a composite variable with four levels: "definite" maternal atopic status ; "latent" ; "probable" ; and "none" .D. pteronyssinus and D. farinae), cat dander, dog dander, horse dander, timothy grass, cladosporium, silver birch, olive, mugwort and nettle. Blood samples were allowed to stand and coagulate in Gel and Clot Activator tubes  for at least 10 minutes. They were then centrifuged at 3000 revolutions per minute for a further 15 minutes. Serum was then stored at minus 40°C until analysis for serum IgE. Results were recorded as either positive or negative to inhalant IgE screen. Individuals were classified as positive if they had IgE to one or more of the above tested aero-allergens.The inhalant screen was a non-quantitative test for specific allergens. The test was positive if it detected antibodies against one or more of the following allergens; house dust mite , by fathers or any other individual inside the home was recorded at recruitment and updated at each follow-up. Exposures to environmental tobacco smoke (ETS) in the household and maternal smoking during pregnancy were combined and classified into three groups. When mothers did not smoke during pregnancy and there was no exposure to household ETS in children up to the age of 10 years, children were categorized as "ETS-0". When mothers did not smoke during pregnancy but household members smoked within the home at some point up to the child's age of 10 years, the exposure status was categorized as "ETS-1". When mothers smoked during pregnancy and the children were also exposed to household ETS at some point up to the age of 10 years, the exposure was categorized as "ETS-2". None of the children had mothers who smoked during pregnancy with no exposure to household tobacco smoke after birth .IL13 polymorphisms, and their interaction on SPT, using generalized estimating equations (GEE). In addition, since SPTs are prevalent outcomes, we did not estimate odds ratios but prevalence ratios (PROC GENMOD with the REPEATED statement and LOG link function in SAS). The association of birth order with IgE and the inhalant screen measured at age 10 was also determined using prevalence ratios (PRs).Serum total IgE at age 10 (dichotomized into ≤ 200 kU/L and >200 kU/L) and inhalant IgE at age 10 (dichotomized into positive or negative) were analyzed as binary outcomes. Because SPT was measured at ages 4, 10 and 18 years, the three measurements for each individual child were correlated over time. To account for these correlations, we estimated the effect of birth order, IL13 SNP interaction terms). The significance level for the interaction effects was set at an alpha level of 0.1, for interaction on a multiplicative scale (log-linear models), and results were presented by stratification when the "birth order by gene" effect was significant. Stratification assesses interaction between IL13 and birth order on an additive scale, meaning that the combined effect is more than the sum of the single effects, whereas multiplicative interaction implies that the combined effect is more than the product of the individual effects.In order to exclude the possible confounding effect of correlated variables, multivariable regression was used to explore the predictive effect of each variable, adjusting for all potential confounders. Assessment of interaction was carried out using backward elimination from the full model  consented to participate in this study. Birth order information was available for 83.2% (1212/1456) of the original birth cohort; skin prick test was performed on 67.4% (981/1456) of the original cohort at age 4, 71.2% (1036/1456) at age 10 and 58.0% (845/1456) at age 18 years. Of all the children who were skin-prick tested, the prevalence of atopy  was 19.7%, 26.7% and 41.1% at ages 4, 10 and 18 years respectively.Serum total IgE measurements at age 10 were available for 65.5% (953/1456) of the original cohort. Comparison of the demographic data between children with and without IgE measurements at age 10 revealed no evidence of selection bias in the major variables used for this analysis; however, children with no IgE measurements had greater environmental tobacco smoke exposure and were more likely to come from the low family social status cluster Table .IL13 polymorphisms were not significantly correlated with atopic markers at ages 4, 10 and 18 years, except for rs2066960, which was a significant predictor of elevated serum IgE (>200 kU/L) at age 10 years (p = 0.011)  at age 10 years Table . UnadjusOther significant predictors of elevated serum IgE at age 10 years in the univariable analysis included maternal IgE (p = 0.009), maternal atopic status (p = 0.006), elevated cord serum IgE p = 0.004) and prematurity (p = 0.008) Table . Similar and premUsing multivariable log-linear regression analysis and after mutually adjusting for potential confounders, there was a significant interaction between rs1800925 and birth order on elevated serum total IgE at age 10 years (p = 0.023). To unfold this interaction, we stratified the analysis by birth order . No other significant associations were found.In the multivariable log-linear regression analysis and after mutually adjusting for potential confounding variables, we identified a statistically significant interaction between rs20541 and birth order on serum specific inhalant IgE positivity at age 10 (p = 0.029). To demonstrate this interaction, we stratified the analysis by birth order Table . The strIL13 polymorphisms with SPT at the different time-points. Multivariable analysis showed significant interaction on a multiplicative scale between IL13 and birth order on SPT positivity at age 10  and age 18  but not at age 4. To further demonstrate and compare these effects on an additive scale, we stratified by birth order at each time-point. Among first-born children, minor allele carrier-ship of rs20541 showed a trend towards a higher risk of skin sensitization at age 4 , age 10  and 18 years . On the other hand, there was no such increased risk of atopy among second-born children at age 4 , age 10  and 18 years . Compared to the referent group, in children with a birth order of 3 or greater, there was also a higher but non-significant prevalence ratio of SPT in children with minor allele carriership of rs20541.We assessed the interaction of IL13 polymorphism on SPT within each birth order category. The stratified analysis showed that the effect of IL13 on SPT at ages 4, 10 and 18 was evident only among first-born children , with borderline significance for second-born children. Children with a birth order of 3 and higher showed an increased but non-significant prevalence ratio of SPT positivity.After confounder adjustment, the multivariable repeated measurement regression analysis showed a significant interaction between rs20541 and birth order on SPT at ages 4, 10 and 18 years at an alpha level of 0.1 p = 0.076). To further describe this interaction, we stratified the statistical model by birth order  at age 4; 94.3% 1,373/1456) at age 10; and 89.6%  at age 18 years. Secondly, children who had IgE measurement results differed only with regard to environmental tobacco smoke exposure and family social status cluster from those who had no IgE measurements , while the more specific reactions to inhalant allergens and skin sensitization are related to the non-synonymous  SNP, rs20541 (exonic SNP).While associations with different SNPs on the same gene are not considered an indication of disagreement ,41,42, wIL13 polymorphisms [interaction between birth order and IL13 polymorphisms. If confirmed by other researchers, this effect modification may in part explain the mechanism of the birth order effect: genetic polymorphisms in the IL13 gene may undergo epigenetic changes in utero due to conditions specific to a first pregnancy compared to subsequent pregnancies. It is now established that the DNA provides the blueprint for the manufacture of all the proteins necessary to create a living organism. Nonetheless, epigenetic modifications provide additional instructions on how, where, and when the genetic information will be used (gene expression). These epigenetic changes generally involve DNA modification such as methylation and acetylation, histone protein modifications, and regulation of gene expression by microRNAs [in utero epigenetic modifications may result in a higher susceptibility to increased total IgE levels and allergic sensitization in first-born children compared to children of higher-order births.Birth order ,14,15 anorphisms -21 have icroRNAs . Such reicroRNAs ,45. InheicroRNAs . Such inIL13 polymorphism was restricted to firstborn children, with individuals carrying the homozygous minor and heterozygous genotypes having a higher relative risk  among firstborns. In addition, there was a lowered relative risk of the rs20451 SNP in second born, and a higher relative risk in children with a birth order of three or greater, although these were not statistically significant. The recurrence of an increased relative risk in children with 3rd or higher order births was not expected. However, since this group is comprised of children with different birth orders (three and higher), it is possible that a long inter-pregnancy interval may modify the intrauterine environment. In support of this hypothesis, Wegienka et al. [We have shown that the effect of a et al.  found thOur findings suggest adverse prenatal programming in firstborn offspring. This impact may be related to immunological differences between a first-born pregnancy and later pregnancies from the same partner, as has been previously documented for the etiology of preeclampsia . HoweverThe advantages of a birth cohort with prolonged follow-up, such as the Isle of Wight cohort, has been discussed in the literature as a necessary means to increase our understanding of genetic diseases, especially atopic disorders . Unlike IL13 gene in relation to atopic outcomes. If we know that the methylation status is affected, it may be possible to develop interventions during pregnancy that could change global or IL13-specific methylation. Thus, these findings may inform research into allergy prevention by identifying which specific conditions may modify the altered expression of the IL13 gene in firstborns when compared to second borns.Finally, future functional genetic research, including gene expression and methylation studies, need to determine whether birth order is related to altered expression or methylation of the The authors declare that they have no competing interests.IUO conceived of the manuscript idea, drafted the manuscript and performed the statistical analysis. WJK provided supervision and guidance in the design, analysis and writing of the manuscript. HZ provided statistical oversight while TSA assisted with the interpretation of genetic results. SE, GR and SHA participated in the design and coordination of the original cohort study, carried out the molecular genetic studies, provided oversight in interpretation of analytic results and participated in all stages of the manuscript writing process. All authors read and approved the final manuscript.


Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth.All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, , astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters.Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age.This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher. Full term newborn babies are known to be on average hypermetropic at birth In developing countries a large proportion of low birth weight babies (LBW: birth weight less than 2500 gms) may be small for gestational age (SGA). If refractive status is related primarily to gestational age, LBW babies could be expected to have a lower incidence of refractive error, as many of the LBW babies are not premature. In the present study, we have looked at the correlation between refractive error and birth weight, head circumference and length of the baby as well as the gestational age. We hypothesized that physical characteristics of the eye at birth, namely the size of the globe, the curvature of the cornea and lens characteristics, and therefore, the refractive error, may be correlated to physical characteristics like weight, length and head circumference more closely than with gestational age. To test this hypothesis we revisited the data on refractive error at birth Of the 603 neonates in the original study The weight of the newborn at birth was measured on an electronic weighing machine accurate up to 10 g. Gestational age was determined from the date of last menstrual period (LMP). If this was not known then gestational age determined by the first ultrasound was considered and if this too was unavailable then gestational age was determined using the New Ballard Score We studied the data from the right eye of each child for correlation of refractive status with gestation, length, head circumference and weight. The difference in MSE between the right and left eye was also studied to look for anisometropia at different gestational age, length, weight and head circumference. The method of testing refractive error has been previously reported in detail Statistical analysis: The mean values, standard deviation, medians, range, and confidence intervals are reported. Simple linear regression analysis was performed to analyze the association of refractive error, mean spherical equivalent (MSE), astigmatism and anisometropia with each of the study variables, namely gestation, length, weight and head circumference. Multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters. The relationship of the study variables  to the three categories of astigmatism  were examined with one-way analysis of variance technique followed by Bonferroni adjustment for multiple comparisons. All statistical analyses were carried out using Stata 9.1 .The various characteristics of the 559 newborns studied are shown in The pattern of astigmatism  is observed to be similar (exact p = 0.26) in these two groups of term and preterm babies Multiple linear regression analysis identified two independent predictors, namely birth weight and gestation, for MSE. Together they accounted for about a quarter of the variation in MSE. To understand further as to which of the two is more important, the mean MSE values were looked at separately for the various strata formed by gestation and weight . It is cNone of the variables other than length was significantly associated with astigmatism in the multiple regression analysis.This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. Our paper shows that the degree of hypermetropia decreases with increasing degree of prematurity with myopia noted in babies below 28 weeks of gestation. There was however only a small no. of preterms under 28 weeks of gestation in our study. To draw a more definite conclusion for this particular age group, a study looking at a much larger number is needed. In the present paper, we have looked at the correlation of refractive errors with birth weight, length and head circumference, in the first week of life among preterm and term newborn babies. In a developing country, there is both a higher incidence of preterm birth  and low birth weight  Cyclopentolate 0.5% is a better cycloplegic agent and has indeed been used in other studies. However, it is found to produce poor dilatation in pigmented irides and needs repeated instillation with the attended higher risk of gastric atony. It was for this reason, tropicamide and phenylephrine was used in our study. Residual accommodation, if any, with the agents we used would have resulted in a variability of the retinoscopy reflex but this was not found in a pilot study.The findings in our study need to be corroborated by findings in other populations. The need for follow up of premature babies for refractive error is well established


We show here, in an unmanaged population of Soay sheep, that female lambs with a male co-twin have reduced birth weight relative to those with a female co-twin, while there was no such effect in male twins. In addition, females with a male co-twin had lower lifetime breeding success, which appeared to be mainly driven by differences in first-year survival. These results show that sex-specific sibling interactions can have long-term consequences for survival and reproduction, with potentially important implications for optimal sex allocation.Males and females often have different requirements during early development, leading to sex-specific interactions between developing offspring. In polytocous mammals, competition for limited resources  Since 1985, individuals in the Village Bay study population have been intensively monitored throughout their lives. Approximately 95 per cent of the lambs are captured for ear tagging and weighing within a few days of birth. Approximately 15 per cent of births are twins, while the other 85 per cent consists of singletons .Data were collected in a long-term study on an unmanaged population of Soay sheep nt) and the year before (nt−1)  if lambs were captured within 7 days after birth . We used linear mixed effect models to test the effects of an individual's sex and its co-twin sex on its birth weight. We controlled for variation in capture age by including it (in days) as a covariate. We included the interaction terms of sex and co-twin sex to test for sex-specific interactions between siblings. After (c)LBS was estimated as the total number of lambs born to a female over her entire life; i.e. only females recorded to be dead were included (mean ± SD = 0.90 ± 2.57 lambs). We used Poisson-lognormal generalized linear mixed models with log link function to estimate the effect of co-twin sex on female LBS. Birth date and residuals of the regression of birth weight on capture age were included as fixed effects. Birth year was included as a random effect. Lamb ID was included as an additional random effect, to account for overdispersion in the data over and above the variance modelled by the fixed effects and by the Poisson random variation around the annual means After controlling for the various variables known to explain variation in birth weight . This si(b)p < 0.001; see electronic supplementary material, table S1), and after taking account of this effect, the effect of co-twin sex was no longer significant .Females with a male co-twin had significantly reduced LBS compared with females with a female co-twin . This re4.It has previously been shown in Soay sheep that having a twin sibling substantially reduces birth weight, leading to subsequent lower first-year survival, which ultimately results in reduced lifetime reproductive success  and 2. Hin utero importantly contributes to the observed pattern. Male Soay sheep lambs are on average heavier at birth than females .Remarkably, ex twins . In Soay


Giant meconium cyst resulting from antenatal bowel perforation is rare and hardly reported in multiple gestations. We found only four documented cases in the electronic literature.We report a giant meconium cyst in an 11-hour-old Nigerian boy of a discordant twin having ultrasonographic and plain radiographic diagnosis and surgical confirmation. Increasing abdominal girth from 35 cm to 41 cm within four hours of admission without ascites, pneumoperitneum and significant bowel distension make us assumed the meconium cyst to be “growing” in size. We reviewed the literature and proposed that where the fibrinous wall of meconium cyst allows for distensibility and the communication between the perforated bowel and meconium cyst persists, the meconium cyst acting as reservoir may continue to “grow” in size without remarkable intestinal distension probably, until the elastic limit is lost.Meconium cyst can occur in twin pregnancy, grow to occupy the abdomen almost completely and may cause neonatal apnoea. The outcome is good post surgery. Meconium cyst results when meconium leaked into the peritoneum from antenatal perforation of the bowel is walled-off by fibrinous adhesion that ultimately becomes a well-defined capsule of granulation tissue if the perforation remains open -4. The eThe advent of ultrasound has resulted in the diagnoses of many cases prenatally and in the early neonatal period ,8. PriorA giant meconium cyst diagnosed on postnatal ultrasonography and plain abdominal radiograph in one of a discordant twin is reported because most of the reported cases of either meconium peritonitis or meconium cyst have been in singleton fetus. We found only four cases documented in association with multiple pregnancies in the electronic literature -10.+ 0, 4 alive, under the supervision of a community nurse, was brought to our Hospital because of a progressively increasing abdominal swelling. Prior to presentation, he had two episodes of non-bilious and non-projectile vomiting. Antenatal care was supervised at a community clinic. Delivery was at 37 weeks 6 days menstrual age and the labour lasted for about 8 hours. Both babies cried spontaneously at birth and required no resuscitation. However, the boy had increasing abdominal distension overtime, vomited on attempted feeding and soon begins to have apnoea. These were the reasons for his referral to our centre.An 11-hour-old Nigerian boyof Yoruba ethnicity, first of a discordant twin delivered at home by a 27-year-old woman, para 3 At presentation, he was dyspoeic (60 cycles per min.), tachycardic (140 beats per min.) and hypothermic (35 °C). The abdomen was grossly distended, tensed and shining. Umbilical cord was tied with thread but appear clean. Bowel sounds were hypoactive. The abdominal girth increased from 35 cm to 41 cm within four hours of admission. The head circumference was 31.3 cm. The chest was clinically clear. He weighed 2.5 kg while the second twin weighs 2.7 kg.Laboratory work ups, which included full blood count, blood culture and serum chemistry were all within normal range.th rib posteriorly.Abdominal ultrasound showed a thick-walled cystic mass occupying nearly the entire abdomen. It has brightly echogenic internal echoes, layering and calcifications . The masExploratory laparotomy revealed a giant meconium cyst , terminaAntenatal perforation of the bowel leading to meconium peritonitis occasionally occurs as a localized, encysted, collection of meconium ranging from a few centimeters in size to huge cysts occupying most of the abdominal cavity when the perforation remains open ,4. FibroThe rapid abdominal distension in our patient post delivery, which culminated into respiratory distress presumably due to diaphragmatic splinting from raised intra-abdominal pressure, necessitated urgent and minimally non-invasive diagnostic radiological work-up with ultrasound and plain radiograph of the abdomen prior to emergency surgery.Plain radiograph is of good diagnostic capability. The radiographic findings may include abdominal distension, intestinal dilatation, pneumoperitoneum, air-fluid levels and calcifications ,4,6. TheThe lucency (gas) within the meconium cyst in this case indicates persistent communication between the perforated bowel and the cyst cavity and was confirmed at surgery. The increasing abdominal distension and respiratory distress in our patient with no commensurate radiographic, ultrasonic and intraoperative findings of bowel distension make us assume a “growing” meconium cyst. Probably where the fibrinous wall of meconium cyst allows for distensibility, proximal bowel dilatation may not be remarkable rather the meconium cyst acting as reservoir may continue, “Growing” in size. We assume that in a “growing” meconium cyst, the site of perforation must act as a one-way valve that allows intestinal emptying without refluxing. Emptying into the cyst may persist until the emptying pressure is exceeded before remarkable intestinal distension can occur. Further study is required to corroborate or refutes our arguments. However, some cases having no bowel distension have been documented ,12.The location of the bowel perforation in our case at the pre atretic segment of the ileum is similar to few other reported cases ,5. The iMeconium cyst can occur in twin pregnancy, grow to occupy the abdomen almost completely and may cause neonatal apnoea. Ultrasonography and plain radiography are invaluable in the diagnosis. We propose a possible explanation for the development of giant meconium cyst, which we have tag a “growing” meconium cyst.


Exploring whether the positive association between birth weight and breast cancer risk differs by other breast cancer risk factors may help inform speculation about biological mechanism. In these data, high birth weight was associated with breast cancer risk in younger and in more educated women, but was not associated overall. The strengths of this resource are the availability of weight from birth records, adult breast cancer risk factor data from three phases of questionnaire follow-up, and a subset of the population receiving very high pharmacologic doses of oestrogen, which could inform some of the speculation about possible hormonal mechanisms.Approvals for the study were obtained from the committees for the review of research involving human subjects at the field centres and the NCI.in situ disease in an additional 11%. Only primary invasive cases were analysed.The NCI DES Combined Cohort Study started in 1992 with the aggregation of prior US cohorts of individuals with medical record documentation of DES exposure and a comparable cohort of unexposed women (=24 years). Information on covariates was obtained from the study questionnaires, obstetrical records or interviews, or from earlier questionnaires from the original cohort studies.Data on birth weight and gestational age were available from obstetrical charts for 80% of the women. For the remaining 20%, these data were ascertained from the mothers at the time of their daughter's original enrollment in the study (the average age of the daughtersFollow-up began on 1 January 1978 (or the date of first enrollment if it occurred later). Person-years accrued until the earliest of the following dates: first breast cancer diagnosis, last known follow-up, death, or return of the 2001 questionnaire. The median number of follow-up years was 23.5 (0.1–25.9 years) for a total of 118 985 person-years.Poisson regression analysis was used to estimate the age-adjusted incidence rate ratios of breast cancer for each category of birth weight and gestational age. A test for trend was assessed by using an ordinal variable for the birth weight categories. To assess confounding, estimates were individually adjusted for each of the covariates. As a hypothesis-generating exercise, interactions of birth weight with the collected covariates were assessed.P<0.0001), BMI , and BMI at age 20 .Birth weight was not associated with attained age, age at first birth/parity, menopausal status, or family history of breast cancer, but was inversely associated with mother's smoking status and use of DES during pregnancy . An inveP for trend=0.69) (P for trend=0.66). These results were similar with simultaneous adjustment for age and gestational age in the birth weight models, or age and birth weight in the gestational age models (data not shown). Estimates changed less than 10% with further adjustment individually for calendar year, and the variables listed in Overall, there was no association between birth weight and breast cancer risk comparing women who weighed <3000 g (rate ratio (RR)=0.93) or >3500 g (RR=1.09) with women who weighed 3000–3499 g at birth (nd=0.69) , and theP for interaction=0.004). However, neither of the estimates was statistically significant and the latter was based on only two exposed cases. There was no evidence of interaction in the association of birth weight with breast cancer incidence by any other breast cancer risk factor, including in utero DES exposure, although there were few cases in many of these subanalyses reflected by unstable estimates and wide CIs (data not shown). In analyses restricted to the DES-exposed women, the risk estimates for birth weight and breast cancer by education and age strata were similar to those observed in the combined group of exposed and unexposed women (data not shown).Among women under the age of 40 years, the RR for women who weighed >3500 g at birth was 2.19  0.83–5.7) compared with those who weighed 3000–3500 g . As the Most studies find evidence of a positive association between birth weight and breast cancer risk, but several have not , regardless of their birth weight, received pharmacologic doses of oestrogen during prenatal breast development. Recent observations that cord blood estrogen levels – reflecting fetal exposure – are not associated with birth weight (In conclusion, while there was no overall association, we found an elevated risk of breast cancer with high birth weight among younger women and those of higher educational attainment, findings consistent with several other observations. If true, these subgroup differences might explain some of the inconsistencies between existing studies of this relationship. In addition, the presence of the association in our DES-exposed population argues against the popular hypothesis that such a mechanism is oestrogen mediated.


Thus, this neuroendocrine response to cytokines constitutes an important immunoregulatory feedback involving the brain.Glucocorticoids are potent inhibitors of inflammation and endotoxic shock. This probably occurs through an inhibition of the synthesis of pro-inflammatory cytokines as well as of many of their toxic activities. Therefore, endogenous glucocorticoids (GC) might represent a major mechanism in the control of cytokine mediated pathologies. GC inhibit the synthesis of cytokines in various experimental models. Adrenalectomy or GC antagonists potentiate TNF, IL-1 and IL-6 production in LPS treated mice. GC inhibit the formation of arachidonic acid metabolites and the induction of NO synthase. They also inhibit various activities of cytokines including toxicity, haemodynamic shock and fever. Adrenalectomy sensitizes to the toxic effects of LPS, TNF and IL-1. On the other hand, GC potentiate the synthesis of several cytokine induced APP by the liver. Since many of these proteins have anti-toxic activities  or bind cytokines, this might well represent a GC mediated protective feedback mechanism involving the liver. Not only do GC inhibit cytokines, but


Squamous cell carcinoma of the liver arising from a non-parasitic cyst is a rare entity of a primary liver tumor with an unfavourable prognosis. We report a case of a patient with a cyst in the right lobe leading to upper abdominal symptoms and respiratory discomfort. Malignancy was not suspected from the clinical findings or repeated cytological examination of the cyst fluid. However, the blood stained brown color of the cyst fluid was unusual. Cyst recurrence after six attempts of conservative treatment with sonography guided drainage over a period for more than one year led to laparotomy with cyst unroofing. Because frozen section from the cyst wall revealed the unexpected finding of squamous cell carcinoma right hemihepatectomy was performed during the same operation. The patient is alive more than four years after surgery without cyst or tumor recurrence. The difficulties in establishing diagnosis are confirmed by the review ofother reports. In the diagnosis and treatment ofsymptomatic non-parasitic liver cysts possible malignancy has to be considered. In case of proven carcinoma radical surgery with partial hepatectomy should be performed.