Hydatid cyst disease is common in some regions of the world and is usually located in the liver and lungs. This report presents two cases of primary hydatid cysts located subcutaneously: one in the medial thigh and one in the left palm between the index and middle fingers.A 64-year-old male farmer visited our hospital because a swelling on the right medial thigh had grown during the last year. Superficial ultrasound and computed tomography revealed a lesion resembling a hydatid cyst. A germinative membrane was encountered during surgical excision. Pathological examination was compatible with a hydatid cyst. The second case involved a 67-year-old male farmer who complained of a swelling that had grown in his left palm in the last year. The preliminary diagnosis was a lipoma. However, a hydatid cyst was diagnosed during surgical excision and after the pathological examination. The patient did not have a history of hydatid cyst disease and hydatid cysts were not detected in other organs. There has been no disease recurrence after following both patients for 3 years.A hydatid cyst should be considered in the differential diagnosis of subcutaneous cystic lesions in regions where hydatid cysts are endemic, and should be excised totally, with an intact wall, to avoid recurrence. Echinococcus granulosus or rarely Echinococcus alveolaris. The main hosts for E. granulosus are predators such as dogs, wolves, and foxes, while intermediate hosts include sheep, goats, and cattle. Humans are a coincidental intermediate host. The disease is more frequent in the Middle East, Central Europe, Australia, and South America, where the intermediate hosts are common. The organs affected most often are the liver (70%) and lungs (10–15%). Other locations are extremely rare [A hydatid cyst is a parasitosis caused by the larval form of nd lungs 0–15%. Ot®) and hypertonic saline. The subcutaneous layers and skin were closed in the standard manner.A 64-year-old male farmer visited our clinic because of a swelling on the medial thigh that had grown during the last year. On physical examination, a mobile, painless, fluctuant, 8 × 9 cm mass was palpated. The overlying skin was normal. The only abnormality in the pre-operative laboratory examination was an increased erythrocyte sedimentation rate (ESR 60 mm/hour). The patient had no history of surgery for a hydatid cyst in another organ. Ultrasound (US) and computed tomography (CT) showed a lesion resembling a hydatid cyst Fig. . During Histopathological examination revealed a hydatid cyst, but no additional hydatid cysts were observed on US or CT of the abdomen and thorax; the indirect hemagglutination test for hydatid cysts was negative. The patient was started on albendazole for 3 months (15 mg/kg/day). No findings associated with local or systemic hydatid cysts were detected during a 3-year follow-up period.®) and hypertonic saline. Total cyst excision and primary closure were performed, and histopathological examination revealed a hydatid cyst. The only abnormality in the pre-operative laboratory examination was an increased ESR (60 mm/hour). The patient had no history of surgery for a hydatid cyst in another organ, and no additional cysts were observed on US and CT of the abdomen and thorax. The indirect hemagglutination test for hydatid cysts was negative, and the patient was placed on albendazole for 3 months (15 mg/kg/day). No findings associated with local or systemic hydatid cysts were detected during a 3-year follow-up period.The other case involved a 67-year-old male farmer who complained of a subcutaneous swelling inside the left palm between the index and middle fingers. Physical examination revealed a subcutaneous immobile 2 × 3 cm mass on the palmar side of the left hand between the thumb and index fingers. Surgical excision was planned with a pre-operative diagnosis of lipoma. A hydatid cyst was considered when a germinative membrane was seen during excision under local anesthesia  to form a solitary hydatid cyst, but that is very difficult. It is very possible that systemic dissemination via the lymphatic route accounts for cases with solitary cysts in uncommon sites . Direct Diagnosing hydatid cysts is very difficult in patients living outside the endemic regions. Because exposure to the contents of the cyst can cause problems such as anaphylactic reaction and local recurrence, making the diagnosis pre-operatively is important. The diagnosis of a palmar hydatid cyst was not considered in our second patient pre-operatively since the mass was very small and this localization is very rare. When the cyst contents were seen during excision, the possibility of a hydatid cyst was then considered. No anaphylactic reaction developed in either patient.The radiological findings of a thick cyst wall, calcification, daughter cysts, and a germinative membrane separate from the cyst wall are findings specific to hydatid cysts . Our firSerology is a useful tool for the diagnosis. The indirect hemagglutination (IHA) test is positive in more than 80% of liver hydatid cysts. However, false negative IHA results can be higher in other located hydatid cyst. In those cases, more specific serologic tests are mandatory. A positive indirect hemagglutination test for hydatid cysts is significant, although negative test results do not indicate the absence of the disease, as in our patients. Therefore, the most important diagnostic tool is the awareness of the physician, particularly for the unusual presentation of the disease.The best treatment option is total surgical excision without opening the cyst. If the cyst cannot be excised without opening, the fluid contents should be removed, the laminated membrane should be totally excised, and the cyst pouch should be irrigated with protoscolicidal solutions . SubcutaHydatid cyst should be considered in the differential diagnosis of subcutaneous cysts in regions where hydatid cysts are endemic. Total excision of the cyst with an intact wall is the best treatment.The authors declare that they have no competing interests.AD is the consultant surgeon who drafted the article and performed the operations. BU assisted in performing the surgery, took the pictures and helped revise the article. CK helped in acquisition of data and technical support. VK performed the literature search and helped in revision. All authors read, appraised and approved the final manuscript.Written informed consent was obtained from the patients before publication of this case series and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Since 1993, many studies on the health of Persian Gulf War veterans (PGWVs) have been undertaken. Some authors have concluded that an association exists between Gulf War service and reported infertility or miscarriage, but that effects on PGWV's children were limited.The present study's objective was to describe the reproductive outcome and health of offspring of French Gulf War veterans.The French Study on the Persian Gulf War (PGW) and its Health Consequences is an exhaustive cross-sectional study on all French PGWVs conducted from 2002 to 2004. Data were collected by postal self-administered questionnaire. A case-control study nested in this cohort was conducted to evaluate the link between PGW-related exposures and fathering a child with a birth defect.In the present study, 9% of the 5,666 Gulf veterans who participated reported fertility disorders, and 12% of male veterans reported at least one miscarriage among their partners after the PGW. Overall, 4.2% of fathers reported at least one child with a birth defect conceived after the mission. No PGW-related exposure was associated with any birth defect in children fathered after the PGW mission. Concerning the reported health of children born after the PGW, 1.0% of children presented a pre-term delivery and 2.7% a birth defect. The main birth defects reported were musculoskeletal malformations (0.5%) and urinary system malformations (0.3%). Birth defect incidence in PGWV children conceived after the mission was similar to birth defect incidence described by the Paris Registry of Congenital Malformations, except for Down syndrome (PGWV children incidence was lower than Registry incidence).This study did not highlight a high frequency of fertility disorders or miscarriage among French PGW veterans. We found no evidence for a link between paternal exposure during the Gulf War and increased risk of birth defects among French PGWV children. In late 1990 and early 1991, approximately 20,000 French troops were deployed in the First Gulf War. Since 1993, many studies on the health of Persian Gulf War veterans (PGWVs) have been undertaken, mainly in the USA and the UK. US and UK mortality studies have shown a lower mortality from all illnesses among Gulf War veterans in comparison to non-deployed veterans and an increased mortality from external causes consistent with patterns of postwar mortality observed in veterans of previous wars . CompareSeveral studies have been conducted on reproductive outcomes -31, mainOne study did not find any difference between the reproductive hormones measured in Gulf War veterans and in controls . HoweverPregnancies fathered by Gulf War veterans took longer to conceive . Conceptet al , keyboaWe used Stata™ statistical software for all analyses. All p values are two sided, and we took values less than 0.05 to indicate statistical significance.First, a descriptive analysis was conducted on PGWV: i) living conditions and exposures during the mission; ii) self-reported infertility disorders and miscarriage that appeared after the PGW mission.Secondly, as data on healthy children were not available (except for the number of children), we decided to perform a case-control study nested within the cohort to determine the effect of PGW exposures on the risk of a father conceiving a child with a birth defect after the war. The date of birth had to be later than nine months after the end of the PGW mission for a child to be considered as having been conceived after the war. A case was defined as a man having had at least one child conceived after the PGW mission and presenting at least one birth defect. Two controls were selected for each case. A control was defined as a man of the same age as the case (± 1 year) who had never had a child with a birth defect but who had had at least one child after the PGW mission. Fathers having had at least one child with a birth defect before the PGW were excluded from this analysis. To minimize recall bias, a control should have reported one hospitalization for at least one symptom of the Hopkins Symptom Checklist  after thFinally, the study provides a description of children born to PGWVs after the Gulf War. Major anomalies were described as Maconochie et al reported . Minor aThe National Commission of Data Processing and Civil Liberty approved this investigation, in conformity with article 15, paragraph 3 of the Law of January 6, 1978, concerning data processing, files, and civil liberty.Most of the 5,666 subjects who completed the questionnaire were male (99.5%), with an average age of 41 years (SD: 6 years) at the time of completion of the survey, and 71% of respondents were still in service. Considering the sample size of female veterans, the results are presented below by gender.The mean age of the 28 women who completed the questionnaire was 44 years (37 to 57 years). They served mainly in military health services (n = 14) and in the Air Force (n = 12). One woman served in the Navy and one in the Army. Six women reported at least one miscarriage after the mission. Nine women reported having at least one child after the mission , ranging from 1 to 4 children. No birth defect was reported in children born after the mission.The main characteristics of the 5,638 male veterans are presented in Table Infertility and reproductive outcomes are described in 5,638 male veterans. Infertility problems  were reported by 48 respondents, mainly Army veterans Table .After deployment, 3,121 veterans fathered at least one child . The number of pregnancies reported per father varied from 1 to 10 pregnancies.After deployment, 682 male veterans (12%) reported at least one miscarriage by their partner, 33 of whom reported a miscarriage before and after the mission. Overall, 135 men (4.3% of fathers) reported at least one child born with at least one birth defect (140 children), of which 4 reported having one child presenting a birth defect both before and after the mission (8 children). After the PGW mission, 131 fathers (4.2%) reported at least one child born with a birth defect, without having conceived a child with a birth defect before the PGW mission.The case-control study of PGW-related exposures on any birth defects included 131 cases and 262 controls. The 262 controls were randomized among the 845 veterans who had reported one hospitalization for at least one symptom (14.9% of participants), and matched for age (+/- one year). Characteristics of subjects in terms of branch of service, rank and military status, and crude and adjusted odds ratios for any birth defects are presented in Table Cases did not differ from controls according to service branch, rank, or military status.Description of PGW-related exposures and odds ratios for any birth defects adjusted for branch of service, rank, and military status are presented in Table vs 64.9%), which did not persist after adjustment for service branch, rank, and military status.Service period and locations for the PGW mission (Iraq and/or Kuwait) were not different for cases and controls. Concerning PGW-related exposures, cases reported an identical exposure to the smoke of oil well fires, sandstorms, chemical alarms, and pesticides. Controls more often reported an exposure to sounding of chemical alarms . Eight babies presented two malformations. These associations were not specific.The different major birth defects of babies conceived after the Gulf War mission are presented in Table The main birth defects reported in babies conceived after the mission were anomalies of the musculoskeletal system  and urinary system anomalies . However, no specific birth defect was found. Only 21 children conceived in the first two years following the conflict presented birth defects, mainly malformations of the digestive system.The birth defect frequencies estimated after deployment were compared to available French data . The 10-year birth defect incidence rate of children conceived after deployment  was not different from the incidence of the birth defect Registry . Figure Compared with the Registry birth defect incidence, no main birth defect was higher in the veterans' children group. Only Down syndrome incidence was statistically lower in the veterans' children group than in the Registry one .In this study, 1% of the Gulf veterans reported fertility disorders and 12% of male veterans reported at least one miscarriage among their partners after the PGW mission. Overall, 4.2% of fathers reported at least one child born with a birth defect after the mission. No PGW-related exposure was associated with any birth defect in children fathered after the PGW mission. Concerning the reported health of children born after the PGW mission, 1.0% of children were born with pre-term delivery and 2.7% presented a birth defect. The main birth defects reported were musculoskeletal malformations (0.5%) and urinary system malformations (0.3%). Birth defect incidence in PGWV children conceived after the mission was similar to birth defect incidence described by the Paris Registry; except for Down syndrome, where the incidence in PGWV children was lower than the Paris Registry incidence.Results are reported with several reservations. Although we sent out two reminders, our study did not have a high response rate, which suggests selective participation by respondents according to health outcome. The French Study on the Persian Gulf War and its Health Consequences aimed to be exhaustive, offering a free medical examination to all veterans provided by the French Government. The media in foreign countries gave massive coverage to complaints lodged due to the health consequences of the Gulf War, so respondents with health disorders, or at least worried about them, were more willing to participate in our study. However, this bias could be partly compensated for by the fact that 71% of respondents were still in service.Data were gathered retrospectively and were based on veterans' self-reported data and were not validated against medical records for healthy veterans or their children. However, it is probable that symptoms or serious diseases requiring specific care or of unusual frequency or intensity were reported more often than events considered as slight or benign.Recall bias can be a serious problem in case-control studies; when pre-recorded written exposure information is unavailable, controls with identical stimuli should be selected  . We condA direct relationship of birth defects to characteristics of the PGW mission could not be shown because i) data were collected retrospectively on a 10-year period, ii) information was based on the declarations of the PGW veterans , and iii) this study can only highlight associations between exposures and diseases and not evidence. Moreover, many children were conceived long after the war itself, personal risk factors  were not examined, and there is a potential for misreporting. No information was available on the use of medication. Results must be interpreted with caution due to the small number of case children for specific birth defects. Despite these major limitations, frequencies shown in French PGWVs were similar to frequencies in the French general population, except for the low frequency of Down syndrome. In our study, dates of birth of the unaffected children were not available and fathers' ages at birth were not known. However, 82% of fathers were 25 to 35 years old during the period covered by the study. Paternal age is related to maternal age and the risk of infecundity, miscarriage, and birth defects seems to increase with paternal age ,40. In tThe results of fertility studies on Gulf War veterans are controversial. The first studies published ,28 did nAuthors reported an increased risk of miscarriage among partners of PGWVs, compared to a control group ,23,25-27Concerning children's health in our study, the frequency of pre-term delivery (1.0%) was lower than frequencies described in other studies on PGW veterans (ranging from 0.6% to 10.9%) ,25,26,30vs 1993–2001), we estimated by simulation that fewer than 700 live births were needed in 1991–1992 . However, this figure did not seem plausible in view of the context (a return home after an overseas mission). Specific birth defect frequencies were lower in our study than frequencies described by Doyle [vs 4.6‰ in our study), or malformations of the urinary system (4.9‰ in Doyle's study vs 3.5‰ in our study). The frequency of renal anomalies (1.4‰) was similar to that described by Araneta [In our study, the frequency of birth defects was slightly lower (2.7%) than the frequencies described in other studies (ranging from 3.6 to 9.0%) -23,25,26by Doyle  in UK PGA combination of genetic and environmental factors may be responsible for 20 to 25% of congenital anomalies . US GulfIn conclusion, this study found the same frequencies of fertility disorders, miscarriage, and health disorders among PGWV children as those described among foreign PGWVs and the French general population. No PGW-related exposure was associated with any birth defect in children fathered after the PGW mission. Our findings are limited by the reliability of self-reported data concerning exposures and health and pregnancy outcomes. This study highlights the importance of prospective data collection for exposures during future foreign operations and epidemiological surveillance of servicemen and women.However, if the fertility disorders and birth defects remain constant over time, a more detailed and focused survey would be required to examine fertility and other aspects of reproduction more thoroughly.The French Study on Persian Gulf War and its Health Consequences was funded by the French Ministry of Defense.CV carried out study design, statistical analyses and drafting the manuscript, MAJ supervised all aspects of study design and statistical analyses, CDV helped to findings interpretation on birth defects analyses, MB participated in study design and carried out data collection, LBC helped revise the manuscript, PB supervised analyses and helped revise the manuscript, RS was the principal investigator and supervised all aspects of study implementation. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Birth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients.3)) was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim). The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis.Information on birth size  from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis.Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival.Poorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF) system is involved in the underlying mechanisms. During the last two decades, it has been shown that birth size is positively associated with breast cancer risk later in life. Thus, birth weight, birth length, and head circumference have all shown positive associations with breast cancer risk in studies that employed measurements from birth records -3. In a Less attention has been given to these factors as predictors of the prognosis among breast cancer patients. Nonetheless, it has been shown that adult obesity is adversely related to prognosis, both indicated as survival and mortality from breast cancer, and this effect appears to be equally strong for women with pre- and postmenopausal disease . On the In this study, we have therefore assessed whether birth size is associated with survival of subsequent breast cancer, and in the analysis, we have adjusted for the influence of known prognostic factors such as lymph node status and tumour diameter.In order to have access to data on birth size, eligible breast cancer patients had to be born in Trondheim or Bergen, Norway. Therefore, we used data from the Norwegian Cancer Registry to identify women with breast cancer who were residents in Trondheim or Bergen at the time of diagnosis. The Central Person Registry, which is administered by Statistics Norway, provided the necessary information on place of residence at birth. That registry maintains continuously updated records on each woman's residential address and the identity of the mother.The information on birth weight and birth length for patients born in Trondheim was collected from the birth archive of EC Dahl's Foundation that served as the major birth clinic in Trondheim from 1910 to 1970. Birth data from Bergen were derived from archives of Bergen Birth Foundation and Midwife School, and later from the Maternity Hospital in Bergen. The information is stored at the Regional State Archives in Bergen. We further used information from the Central Person Registry of Norway to verify individual linkage between women of the study and their birth records.3). The correlation coefficient between ponderal index and birth length was 0.00, and between ponderal index and birth weight it was 0.66, indicating that birth length and ponderal index may be considered independent of each other.To be included, patients had to be singletons born at term; birth length was restricted to range from 46 to 55 cm, and birth weight could range from 2000 to 5000 grams. In the analysis, we only included patients who were treated with modified radical mastectomy. Among 373 potentially eligible patients, we could include 331 patients in the analysis for whom we had sufficient information from birth. Perinatal information was abstracted from birth records and included birth weight (grams) and birth length (centimetres). As a measure of body mass, independent of length, ponderal index was calculated as birth weight divided by the cubed value of birth length (kg/length(m)Breast cancer specimens were examined at the Department of Pathology, St Olav's University Hospital in Trondheim, or at the Department of Pathology, Haukeland University Hospital in Bergen. Information on tumour diameter and lymph node status at diagnosis was abstracted from the pathology reports.3 and 29.1 kg/m3.In the statistical analysis, birth length, birth weight and ponderal index were categorised into approximate quintiles, and in subsequent analyses, the second, third and fourth quintile were combined into one category because of the range between the second and the fourth quintile was small. Thus, each variable had three categories: the first category was the lowest quintile; the second category was a combination of the second, third, and fourth quintile, and the third category was the highest quintile. For birth weight, the first quintile included weights below or equal to 3050 grams, and the fifth quintile included birth weights above 3850 grams. The corresponding threshold values for the lowest and highest quintile of birth length were 48 cm and 52 cm, and for ponderal index, it was 25.0 kg/mAll patients were followed up by linkage to data from the Causes of Death Registry at Statistics Norway. Follow-up started at the date of diagnosis, and median follow-up was 108 months. Women were censored at the time of death, or at the end of follow-up. For patients in Trondheim, follow-up ended on December 31, 1999, and for patients in Bergen, follow-up ended on December 31, 2003. Death from breast cancer was the primary endpoint, and no patient was lost to follow-up. The Cox proportional hazards model was used to estimate the relative risk of dying (hazard ratio) from breast cancer related to the categories (see above) of birth weight, birth length and ponderal index. The Cox model is based on the assumption that death rates between categories of patients are constant over time. No serious deviations from the proportionality assumption were found, based on plots of the log minus log survival function (not shown). In a multivariable analysis, we adjusted for place of birth and year of diagnosis, and in additional analysis, we also took lymph node status and tumour diameter at diagnosis into account. All statistical analyses were done using SPSS, version 11.0 for Windows .The study was approved by the regional committee for ethics in medical research.Patient characteristics are presented in Table Since ponderal index and birth length play independent roles, both variables were included in the subsequent multivariable analyses Table . In addiWe have studied whether birth size is associated with the prognosis of breast cancer patients, and found that women with high birth length had poorer outcome than women with shorter length at birth. Specifically, women who were 52 cm or longer at birth had nearly twice the risk of dying from breast cancer compared to women who were shorter than 48 cm at birth. This association was not reduced after taking ponderal index, lymph node status, tumour diameter and place of birth into account. We found no association with survival related to birth weight or ponderal index.In prognostic studies, predictors are usually assessed at the time of diagnosis, and patients are subsequently followed up in relation to outcome, which is typically time to death  from the specified disease under study. In this study, however, measurements of birth size were made decades before the diagnosis (on average 50 years earlier). In the literature, there is no evidence that indicators of birth size have any influence on the prognosis of breast cancer once the diagnosis is established, and previously, no study has assessed survival of breast cancer related to birth size. However, given the magnitude of the association that we observed for birth length, sources of bias that may explain the finding should be carefully considered.It is conceivable that better prognosis in one subgroup of patients could be due to better treatment quality. Birth length is positively correlated with adult height, and hence with socioeconomic status ,11. If qAnother possible source of bias could be that the association of birth length with adult socioeconomic status, including higher education, could lead to earlier diagnosis in women with high birth length. This possibility could result in lead time bias, where survival from diagnosis to death would be longer among patients with high birth length compared to women with shorter birth length, who may be diagnosed at a later stage. Also under this scenario, however, the poorer outcome in patients with high birth length is likely to be underestimated.th century may also be a concern. In an attempt to take effects of calendar time (period) into account, we adjusted for year of birth, but this did not influence the estimates of effect. However, this adjustment may not be sufficient to account for secular changes in birth length.The secular increase in birth length that took place in the 20It is also possible that important but unmeasured confounding factors could explain the poorer outcome of patients with high birth length. For such a factor to be of practical interest, however, it would have to be strong, and substantially influence breast cancer survival. Few known prognostic factors meet these criteria, and they are typically variables that describe the stage of the disease at the time of diagnosis, and therefore, these are not factors that could influence birth lenth. In the analysis, we adjusted for lymph node status and tumour diameter, but the adjustment did not substantially influence the results. However, body weight is a factor that does influence the prognosis of breast cancer patients . Birth lin utero and the development and prognosis of later breast cancer, these results may be helpful in guiding investigators towards prognostic mechanisms. The relatively strong association of birth length, indicating longitudinal growth, may suggest that the insulin like growth factor (IGF) system is involved in the underlying mechanisms.It is difficult to see any practical implication of the finding that high birth length is associated with a poorer prognosis of breast cancer. Nonetheless, by establishing a link between conditions that operate The authors declare that they have no competing interests.BOM and LJV collected the data, and all three authors have contributed to the analysis of the data, interpretation of the findings, and to the writing of the manuscript. All authors have seen and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/115/prepub


Moderate increased risk of both ALL and AML was associated with birth weight 3500 g or more. For ALL, however, there was evidence of effect modification with birth weight and maternal prepregnancy weight. High birth weight was associated with ALL only when the mother was not overweight while heavier maternal weight was associated with ALL only when the infant was not high birth weight. Increased pregnancy-related weight gain was associated with ALL. For AML, birth weight under 3000 g and higher prepregnancy weight were both associated with increased risk. These findings suggest childhood leukaemia may be related to factors influencing abnormal fetal growth patterns.There is mounting evidence that childhood leukaemia is associated with high birth weight, but few studies have examined the relationship between leukaemia and other perinatal factors that influence birth weight, such as maternal weight or gestational weight gain. This case-cohort study included 916 acute lymphocytic leukaemia (ALL) and 154 acute myeloid leukaemia (AML) cases diagnosed prior to age 10 years between 1985 and 2001 and born in New York State excluding New York City between 1978 and 2001. Controls ( Leukaemia is the most common form of childhood cancer. There is strong evidence that at least some childhood leukaemias that arise before the age of 14 years have prenatal origins . MaternaWe used existing public health surveillance data to perform a case-cohort study of leukaemia and perinatal risk factors. We hypothesised that high birth weight, first born status, older maternal age and history of prior fetal loss would be associated with the risk of both ALL and AML. The data collected on the New York State birth certificate also allowed for exploratory analysis with respect to factors associated with birth weight and fetal growth. In addition to birth weight and gestational age, several risk factors for macrosomia are available from the New York State birth records, including maternal diabetes, multiparity, prior history of a macrosomic infant, postdate gestation, maternal weight, and pregnancy weight gain.Leukaemia cases were ascertained from the New York State Cancer Registry. All cases age 1 month to 9 years diagnosed with acute leukaemia between 1985 and 2001 while resident of New York State and born in New York State excluding New York City were eligible to be included in the study. Children with leukaemia diagnosed subsequent to another form of cancer were excluded. Eligibility was determined by matching the leukaemia cases to the electronic birth files of children born in New York State between 1978 through 2001. Because the birth certificate used in New York State differs from the certificate used in New York City and other states, children who were found to have been born in New York City or out-of-state were excluded, as were children who were not matched to electronic birth certificate records. Leukaemias were grouped into ALL and AML based on the ICD-O-3 version of the International Classification of Childhood Cancers  were also excluded, because cases diagnosed at less than 1 month of age were excluded from the case series.The independent variables for this study came from the birth certificates of the cases and controls. The birth certificates are completed by the staff at the hospital where the child is born. Data from the birth certificates are routinely abstracted and entered onto the electronic master live birth file, and are available for the birth cohorts included in this study (1978–2001). The birth certificates underwent major revisions in 1988 and 1993. In addition to changes in the birth certificate itself, the data items available on the master birth file have also changed, as has the coding of individual variables. Owing to these changes, some independent variables were not available for analysis for all cases. For example, maternal height was not collected on the New York State birth certificates until 1993, and therefore maternal body mass index could not be calculated for 75% of leukaemia cases and 81% of controls. Maternal prepregnancy weight was collected starting in 1988, and was missing for a similar proportion of cases and controls born between 1998 and 2001 . Maternal weight and weight gain were recorded in pounds on the birth certificate and converted to kilograms for this analysis. There was evidence of end-digit preference in reporting weight gain in pounds, with modes at 20, 25, 30 and 40 pounds. We used these modes for cutpoints in the analysis, which resulted in unusual weight gain categories when reported in kilograms.This study design was a case-cohort study; therefore, the odds ratio provides an estimate of the cumulative incidence (risk) ratio . We defiThere were 1102 ALL cases diagnosed in New York State excluding New York City who were eligible to be included in the study. Birth certificate matches were made for 916 cases, resulting in a match proportion of 83%. The estimated match proportion was slightly higher for cases diagnosed ages 0–4 years (87%) compared to cases diagnosed 5–9 years of age (76%).P=0.0015), and the adjusted odds ratio associated with a 1000 g increase in birth weight as a continuous variable was 1.25 . This association did not vary by age. The adjusted odds ratio for high birth weight for ALL diagnosed within the first 4 years of life was 1.18 , while the adjusted odds ratio for diagnosis at ages 5 to 9 years was 1.15 . The test for trend, however, was not statistically significant for ALL diagnosed at ages 5–9 years.The birth weight distribution of ALL cases and controls is presented in P=0.03) and for diagnosis prior to the age of 5 years (P=0.002). Body mass index classified as overweight or obese (>25) was associated with an adjusted odds ratio of 1.44  for ALL diagnosis prior to the age of five, relative to body mass index of 20–24. Since maternal height was not collected prior to 1993, maternal body mass index was not available for the ALL diagnosed at an older age. There was evidence of interaction between maternal prepregnancy weight and ALL as well (P=0.006). These results varied slightly by age at diagnosis, although the number of cases became sparse . The pattern of increased risk with more weight gain was consistent across the two age groups examined, although the odds ratios did not reach statistical significance for leukaemia diagnosed at ages 5–9 years. When dichotomised into weight gain of more than 14 kg, relative to <14 kg, the adjusted odds ratio for ALL was 1.31 . For ALL diagnosed prior to the fifth birthday, the adjusted odds ratio was 1.26  and for ages 5–9 it was 1.46 .Higher maternal weight gain during pregnancy was also associated with ALL , and theMaternal diabetes was associated with nonsignificant increased risk of ALL after controlling for the other weight factors. For ALL diagnosed prior to the age of 5 years, older maternal age was associated with increased risk, but no increased risk was observed for older age at diagnosis. Other factors examined, but which were not associated with risk of ALL in the multivariate analysis include paternal age, first born status, number of previous live births, maternal history of prior fetal loss, publicly funded financial assistance during pregnancy, method of delivery or use of obstetric procedures during pregnancy and delivery, infertility treatment, maternal smoking or drug use, other maternal medical risk factors such as hypertension, or infant medical risk factors such as birth injury or assisted ventilation (data not shown).There were 186 AML cases eligible to be in the study, of whom 154 matched to birth records, resulting in an estimated match proportion of 83%. The cell types of AML included in this study included AML, not otherwise specified (96 cases), acute promyelocytic leukaemia (12 cases), acute myelomonocytic leukaemia (15 cases), acute monocytic leukaemia (16 cases), acute megakaryoblastic leukaemia (11 cases) and four cases with other AML cell types.P=0.41). Additionally, higher weight gain during pregnancy was not associated with AML. In fact, there was a trend towards decreasing risk with increasing weight gain, and the test for trend was borderline statistically significant (one-sided P for trend=0.046). Older maternal age was also associated with increased risk of AML. The adjusted odds ratio for maternal age 40 years or older, relative to 20–29 years of age, was 3.68 . As with ALL, we did not observe associations between AML and the other maternal or infant risk factors examined (data not shown).Both low birth weight and high birth weight were associated with increased risk of AML, as was heavier prepregnancy weight . Owing tper se, are involved in the mechanism by which birth weight is associated with ALL. These findings warrant further study, since our evaluation of this interaction was exploratory in nature, and limited to births occurring between 1988 and 2001.A recent meta-analysis of 18 studies from the 1940s onward found higher risk of ALL with birth weight of over 4000 g   and 29% increase in risk per 1000 g increase in birth weight. For AML, however, there was evidence of heterogeneity, with two studies showing a nonsignificant protective effect of high birth weight , which is associated with higher birth weight and hypothesised to stimulate myeloid and lymphoid cells . By sampling the controls from the birth cohorts, we are assuming that the controls had they developed cancer, would have been ascertained as cases in the study, and that no controls leave the risk set due to death. Controls who develop cancer may be missed if they migrate out of New York or, less likely, if they were unreported to the state cancer registry. Childhood mortality is associated, either directly or indirectly, with several of the perinatal factors being studied, including infant birth weight and maternal age. After the immediate postnatal period, childhood mortality is low . DespiteUse of birth certificate data for ascertaining perinatal exposures reduces the potential for differential misclassification; since all measurement is made prior to diagnosis and measurement does not rely on parental recall of pregnancy history. Birth certificates, however, may be problematic for epidemiologic studies due to problems with completeness and validity . In a stBy using the birth certificate data, we were able to examine a number of factors related to infant's birth weight, some of which have not been reported on in previous studies. Our findings related to maternal weight and pregnancy weight gain are therefore exploratory, but, given the high prevalence of overweight and obesity, the possible association with childhood leukaemia should be examined in other cohorts. Maternal weight and height, as well as pregnancy weight gain, were added to the United States standard birth certificate in 2003. While the use of the birth certificate for epidemiologic studies has been questioned, the future availability of these data may promote cost-effective, population-based studies of perinatal risk factors for childhood cancer.


High birth weight has serious adverse impacts on chronic health conditions and development in children. This study identifies the social determinants and obstetric complications of high birth weight adjusted for gestational age and baby gender.Pregnant women were recruited from three maternity hospitals in South-East Queensland in Australia during antenatal clinic visits. A questionnaire was completed by each participant to elicit information on eco-epidemiological exposures. Perinatal information was extracted from hospital birth records. A hierarchical mixture regression model was used in the analysis to account for the heterogeneity of birth weights and identify risk factors and obstetric complications of births that were large for gestational age. A generalized linear mixed model was used to adjust for (random) "community" effects.Pre-pregnancy obesity , previous pregnancy , and married mothers  were significantly associated with large for gestational age babies. Subsequent complications included the increased need for delivery by caesarean sections or instrumental procedures , resuscitation , and transfer to intensive/special care nursery . Communities associated with a higher proportion of large for gestational age births were identified.Pre pregnancy obesity is the principal modifiable risk factor for large for gestational age births. Large for gestational age is an important risk factor for the subsequent obstetric complications. The findings improve the evidence-base on which to base preventive interventions to reduce the impact of high birth weight on maternal and child health. All women waiting for third trimester antenatal clinic appointments at each of the locations were approached by research trained midwives, provided with a detailed explanation of the study aims and invited to participate in the study. Written informed consent was obtained for release of hospital perinatal data related to the birth of their child, completion of a participant baseline survey and for individual follow-up. Ethics approval for participant recruitment and follow-up of the 'Environments for Healthy Living' birth cohort was obtained from the Griffith University Ethics Committee (Reference number: MED/16/06/HREC) and the Human Research Ethics review Committees of the three participating public maternity hospitals in the study area .A questionnaire was completed by each participant to elicit information on demographics, socioeconomic status, family structure and relationship, neighbourhood and community connectedness, maternal smoking and drinking behaviour, and the usage of supplements and recreational substances during pregnancy. Perinatal information was extracted from hospital birth records. The Environments for Healthy Living study is based on an ecological model of causation, which attempts to investigate effective social and economic approaches for improving the health of disadvantaged populations and contributing to overall health and wellbeing of populations. A wide variety of health-related exposures and outcomes are measured at baseline and during subsequent follow-up period. The present research extracts variables collected at baseline under the following eco-epidemiological headings: (1) Demographics; (2) Socio-economics; (3) Psychological and behavioural; (4) Social network and neighbourhood; (5) Birth procedures; and (6) Neonatal. The first four eco-epidemiological categories are potential risk factors for large for gestational age births. Variables in the last two categories are adopted to assess potential obstetric complications of delivering large for gestational age babies. All these variables are included in the subsequent analyses.Identification of risk factors for large for gestational age births is usually undertaken using a logistic regression approach with dichotomous outcomes of large for gestational age defined by birth weight percentile for gestational age . The larWith the hierarchical mixture regression model, a generalized linear mixed model (GLMM) was used to adjust for inter-community variations (via multilevel modelling) , where tFor the mixture regression modelling presented in the Appendix, we first estimated the unknown parameters in the component densities with the adjustment for gestational age and baby gender. Based on the fixed estimated parameters in the component densities, risk factors were then included into the logistic regression function in steps, where each step corresponds to a single category of risk variables detailed in the study design above. Interactions between variables were considered at each step. For each category of risk variables, we performed the analysis included only individuals for which all variables in the category were present. Variables that were significant at 10% level (two-sided) within each category were entered into the final model for the determination of risk factors on the proportion of large for gestational age births. Obstetric complications of large for gestational age births were then determined by including the complication variables into the final estimated hierarchical mixture regression model via logistic regression.The proportion of large for gestational age births in each community was calculated by averaging the estimated posterior probability of large for gestational age for all individuals in that community; see the Appendix. The estimated proportion of large for gestational age births was then compared to the unadjusted proportion of large for gestational age births, which was the estimated proportion of large for gestational age births in all regions without adjusting for the risk factors. Communities with more than ten participants and the proportion of large for gestational age births being higher than the unadjusted proportion of large for gestational age births were identified. These communities were associated with a higher than average proportion of large for gestational age births. Their characteristics in twelve pre-determined community profiles were explored based on the 2006 Australian Census of Population and Housing Community Profile data and the matching digital boundary base maps in generic Geographic Information System format .During the first three recruitment phases of the study (November 2006 to August 2008), the total number of mothers approached was 3321, of whom 1553 women (46.8%) agreed to participate and 1565 babies have been registered with the study (including twelve sets of twins).The baseline characteristics of the recruited cohort are displayed in Table th and 95th percentiles of Australian national birth weights at gestational age of 40 weeks from 1991 to 1994, which are 4170 g and 4340 g, respectively, for singleton males, and 4000 g and 4170 g, respectively, for singleton females [The adjusted mean birth weights at gestational age of 40 weeks for the first subgroup  are 3619 g (95% CI = 3580-3659) for males and 3488 g (95% CI = 3451-3524) for females. For the second subgroup , they are 4394 g (95% CI = 4231-4556) and 4249 g (95% CI = 4039-4458) for males and females, respectively. For comparison, we quote the 90The adjusted odds ratios of large for gestational age births for each category of risk factors are provided in Table There is an increased likelihood to have a large for gestational age baby  for mothers who are categorized as obese during pre-pregnancy based on maternal pre-pregnancy BMI  that are associated with a higher proportion of large for gestational age births. These nine communities  but a lower proportion of migrants moving in the communities . Of substantial importance is the finding that three of the communities had a large positive community effect even after controlling for identified risk factors. While these findings will have the potential to pinpoint where improvements can be made within the community to reduce the impact of high birth weight on chronic health conditions and development in children, further validation on the findings are required when more data become available. The fourth-recruitment phase of the Environments for Healthy Living study has been completed and subsequent recruitment is scheduled for future years. This new birth cohort will help targeting interventions to reduce the escalating burden resulting from high birth-weight in Australia. It will also enhance the power to explore further the ecological determinants of large birth-weight and confirm research findings in other populations worldwide.In this study, the mixture model assumed that the observed birth weights came from a population that consisted of two components corresponding to the appropriate for gestational age and large for gestational age subgroups. Thus we circumvented a major limitation in previous research in that the mixture modelling approach requires no prehoc threshold  to definGiven there was complete follow up of subjects between the antenatal ascertainment of explanatory variables and the birth weight and obstetric outcomes the internal validity of the project is strong. The external validity of the results may be compromised by the sample recruitment method that did not engage women who are at risk for delivering babies with low birth weight. Similarly, women using private maternity services  and those with high risk pregnancies referred to specialist care are not captured in the sample. These shortcomings have been addressed in the analysis as described in the methods section by eliminating the group of low birth weights or gestational age smaller than 37 weeks.In the analysis, we did not include maternal morbidities such as diabetes and hypertension as this information was not available for approximately 30% of the cohort due to differences in hospital perinatal data collection. As the national prevalence of these maternal co-morbidities are generally quite low , the nuPre pregnancy obesity is the principal modifiable risk factor for large for gestational age births. Large for gestational age is an important risk factor for the subsequent obstetric complications. The findings from this new cohort study in Australia improve the evidence-base on which to base preventive interventions to reduce the impact of high birth weight on maternal and child health, and confirm research findings in other populations worldwide.With the Environments for Healthy Living study, follow-up routinely occurs when each child reaches 1 and 3 years of age. Participating mothers are mailed a questionnaire eliciting details on eco-epidemiological exposures and infant health and developmental outcomes including chronic markers for asthma, cardiovascular disease, and diabetes. In this research, 104 out of 1440 infants are classified as large for gestational age using the mixture modelling approach. Further study will focus on the comparisons of health and developmental issues between this group of children and the other who are not born large for gestational age. This research will improve the evidence base for the long-term health consequences of large for gestational age infants. Future data linkage with Medicare and related health data will also allow identification of health outcomes in this cohort. The longitudinal nature of the Environments for Healthy Living study has the advantage of being able to identify health and development issues in children in their early part of the life course, implement interventions that may minimize obesity problems among children and measure the long-term chronic disease problems in this group. Further research will compare maternal post-pregnancy weight retention between these two groups, as there is evidence that women retain their weight post-pregnancy have an elevated risk of entering their next pregnancy either overweight or obese ,42.The authors declare that they have no competing interests.SN originated the research, led the design and implementation of mixture modelling, conducted the statistical analyses, and led the writing of the article. AO advised on the obesity, obstetrics, and gynecology aspects of the study. AS, CC, JS, and RM originated the Environments for Healthy Living study and supervised all aspects of its implementation. All authors assisted with conceptualizing ideas, interpreted research findings, and contributed to the writing of the article. All authors read and approved the final manuscript.ij ydenote the baby birth-weight of the jth individual living in the ith community. With the mixture framework, the observed birth weights are assumed to have come from a mixture of two groups  in some unknown proportions that sum to one [Let m to one . A two-cjth individual belonging to the second component corresponding to the subgroup of large for gestational age and kϕ is the kth component-density function . The proportion π is specified as a logistic function of where ij yand i Urepresents the unobservable random effect due to the ith community affecting on the proportion π. These (random) community effects are taken to be normally distributed with zero mean and variance λ [i Uindicates an increased proportion of large for gestational age births in a community. It is further assumed that the component densities are normally distributed with a common variance σ2 [ij xcorresponding to the variables of gestational age and baby gender. The posterior probability of a large for gestational age birth for the jth individual in the ith community is given by i nbe the number of participants in the ith community, the proportion of large for gestational age births in the ith community is given by the averaged posterior probability where riance λ . A positiance σ2 , and theapproach  via the approach . In partapproach . Model sapproach . A FortrThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/460/prepub


We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 : 3.8–17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0–2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3–6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients. In western countries many women postpone childbearing for personal or professional reasons  , low birth weight at term , stillbirth (delivery of a dead foetus at 28 completed weeks of gestation or later in pregnancy), male proportion of newborns, and birth weight. Data on potential confounders included maternal age, parity, gestational age, and calendar period of the birth. Data about congenital abnormalities  diagnosed during the first year after the birth were collected from the Danish Hospital Discharge Registry, established in 1977, with records of all discharges from Danish hospitals. The recorded information includes the civil registration number, dates of admission and discharge, and up to 20 discharge diagnoses, using the International Classification of Diseases . Group 3 included births delivered by women who were diagnosed with breast cancer after delivery . If a woman gave birth more than once in this 2-year period, only the last birth before the cancer diagnosis was included. We computed the difference between the male proportion of newborns of women with breast cancer and that of newborns of matched comparison mothers with 95% confidence intervals (95% CI) for these differences. We estimated the prevalence ratios (PR) using prevalence odds ratios and 95% CI for preterm birth, low birth weight at term, stillbirth, and congenital abnormalities by logistic regression modelling. Stillborn children were excluded from the analyses of preterm birth, low birth weight at term, and congenital abnormalities. We adjusted for maternal age, parity, and calendar period of the birth. PRs for congenital abnormalities were additionally adjusted for gestational age. For births in Groups 1 and 3, we repeated the analyses in strata of boys and girls to examine if sex of the child modified the PR estimates. For births in Group 1, we evaluated whether treatment of the mother modified the PR estimates by repeating the analyses in strata of births of women treated with surgery alone and births of women who received other treatment .We classified the births of women with breast cancer according to time of cancer diagnosis in relation to pregnancy. We used multivariate regression analysis to estimate differences in mean birth weight adjusted for maternal age, parity, gestational age, and calendar period of the birth. Stillborn children were excluded from this analysis.All analyses used SAS software, version 8.2.The study was approved by the Danish Data Protection Agency (record no. 2003-41-2833).Descriptive data on Groups 1, 2 and 3 and their matched comparison births are shown in For births delivered by women in Group 3, the median number of days from date of the birth until date of cancer diagnosis was 417 days (range: 1–729 days).vs 52%, difference=−2.2%,  for Group 1, 49 vs 52%, difference=−3.4%,  for Group 2, and 53 vs 51%, difference=2.5%,  for Group 3).We evaluated the proportion of male newborns of women with breast cancer compared with that of newborns of unaffected mothers (50 We examined the association between maternal breast cancer and adverse birth outcome in a nationwide cohort and found little difference in the occurrence of preterm birth, low birth weight at term, stillbirth, or congenital abnormalities, compared with the comparison cohort, among newborns of women who were diagnosed with breast cancer before pregnancy.The eight-fold increased odds of preterm birth for newborns of women who were diagnosed with breast cancer during their pregnancy reflected a higher rate of elective early delivery, probably to allow an earlier start of cancer therapy. After adjustment for gestational age, there was a 240 g reduction in mean birth weight for newborns in this group. The association with preterm birth in Group 3 may be explained by suboptimal intrauterine conditions caused by a preclinical cancer. In this group, only boys had increased odds of low birth weight at term, suggesting that male foetuses are more vulnerable than female.Our data are derived from a uniformly organized health care system with complete cancer and birth registration. Some selection problems are possible, however. If women with breast cancer had more miscarriages or induced abortions caused by foetal abnormalities than comparison mothers, this phenomenon could explain why we found no increased risk of congenital abnormalities. It has been suggested that exposure to severe periconceptional life events might reduce the male proportion of offspring, partly because of differential abortion of male embryos (A recent study found that treatment data recorded in the Cancer Register are of varying quality (Hospital discharge data are not always coded correctly (Our finding of an increased risk of giving birth preterm for women who were diagnosed with breast cancer during or shortly after pregnancy corroborates the results of two earlier studies (In conclusion, this is the first population-based cohort study of birth outcome in women diagnosed with breast cancer before pregnancy, and the largest cohort study to date of birth outcome in women diagnosed with breast cancer during or shortly after pregnancy. Overall, our results are reassuring regarding the risks of adverse birth outcome for women with breast cancer.


Exposures were ascertained by interview, birth, and growth records. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Current height and age- and sex-specific height percentiles were not associated with osteosarcoma risk. Male cases, however, appeared to have an earlier adolescent growth period, and earlier attainment of final height , whereas earlier puberty appeared protective with ORs of 0.41 (95% CI 0.18–0.89) and 0.68 (95% CI 0.31–1.5) for developing facial and pubic hair, respectively. High birth weight was associated with an elevated osteosarcoma risk , although there was no trend in risk with increasing weight. These data provide some evidence that osteosarcoma is related to size at birth and in early adolescence, while earlier puberty in male subjects may be protective.Osteosarcoma incidence patterns suggest an aetiologic role for perinatal factors, and growth and development. Osteosarcoma patients ( There are few established osteosarcoma risk factors apart from early exposure to high-dose radiation, and Paget's disease, hereditary retinoblastoma, and Li–Fraumeni Syndrome . An excein utero period through puberty and adolescence.In this study, we focused on the associations of osteosarcoma with factors related to growth and development from the Participants were drawn from orthopaedic surgery departments in 10 US medical centres between 1994 and 2000 . Cases were patients with newly diagnosed primary osteosarcoma admitted for evaluation of eligibility for limb salvage surgery. Controls were orthopaedic patients from the same departments with benign tumours (26%), or non-neoplastic conditions such as inflammatory diseases, cysts, and trauma . Nurse coordinators were responsible for control selection by identifying the next patient matching the case on age (+/−5 years), sex, hospital, and distance from the respective medical centre based on the participant's residential zip code. Pathology reports from surgery and/or biopsy were obtained for all cases and for controls for whom this documentation was applicable to confirm diagnosis, whereas hospital medical records confirmed diagnoses for controls without a pathology report .Institutional review boards at each of the medical centres approved this study, and informed consent, which included a check list for a questionnaire, blood draw, and toenail collection, was obtained from all participants. Of eligible cases, 13.6% were not enrolled and a further 3% declined to participate in any of the study components. Of those enrolled in the study, 93.5% of cases and 98% of controls completed interviews. Reasons for non-participation in the questionnaire component included refusal, death, extreme illness following surgery and failure to return for follow-up care. The present analysis was restricted to 169 cases and 144 controls less than 40 years of age to focus on the aetiology of the adolescent-young adult peak in osteosarcoma incidence.Interviews ascertaining information on growth and development, physical activity, and medical history were conducted in the hospital, clinic, or ward with cases after surgery, and after surgery, or other therapy in controls. A supplemental interview on pregnancy exposures was conducted with parents of participants less than 20 years of age, whereas participants over 20 were asked directly.Participants 9–21 years of age were asked to give consent for growth records acquisition. Of 109 cases and 91 controls, respectively, all of the 78 (71.5%) and 57 (62.6%) participants who reported a regular health-care provider gave permission for contact, and a total of 402 growth records were obtained for 49 cases and 46 controls (average of 4.2 records per participant). Growth records validated participants' self-reports of height  compared with their peers at various ages. Among the combined cases and controls, mean height from records was 9% lower and 1.5% higher among participants who reported being shorter and taller, respectively, compared with being about the same height as their peers at age 9 or 10. Similarly, recorded height was 7% lower and 4.5% higher at age 12 or 13, and 3.5% lower and 6% higher at age 15 or 16. Results were similar when evaluated separately for cases and controls.n=154) of cases and 99% (n=139) of controls providing permission. For states where at least six participants were born records were obtained for a total of 289 participants. Equal proportions of cases  and controls  were missing information in the birth records for pregnancy length. Pregnancy complications were missing for 54% (n=85) of cases and 59% (n=83) of controls, and of those with these data, complications were rare (two cases/five controls). Birth weight as reported by the participant or mother  and from records  were highly correlated in those with both sources of information . Therefore, reported birth weight was used when birth records were unavailable.US born participants were asked for their consent to acquire birth records from state vital records offices with 97%  and controls (62%) were under 20 years of age, and they were comparable in sex and race/ethnicity . Cases hvs 17+ years), but with an elevated risk in male subjects (OR=7.1 CI=1.6–50 for <19 vs 19+) . The association of participant's height percentile with risk showed no consistent pattern in any subgrouping according to mother's height (data not shown).Neither height percentile nor absolute height was associated with osteosarcoma risk . In partCases appeared less likely to be shorter than their peers at ages 9–10 and 12–13, and more likely to be taller at ages 15–16, compared with being about the same height . The redvs <4/week), the OR were generally elevated in female subjects, in particular, at ages 15 or 16 , whereas there was no association in male subjects (data not shown). Excluding controls whose condition on study entry was fracture attenuated the elevated estimate for more frequent activity in female subjects .There was no consistent association between sports participation at various ages during childhood and osteosarcoma risk (data not shown). Comparing frequent with less frequent activity ; with further exclusion of fractures occurring within 2 years of questionnaire completion the OR was 0.65. The site of prior fracture was examined to identify whether for any case, the tumour occurred in the same bone; they matched in only two cases (within 1 year and 15 years of diagnosis).Diagnostic or therapeutic radiation before the present illness was not associated with osteosarcoma risk . Radiation exposure was mainly in the form of routine medical X-rays (88% of cases and 87% of controls).vs 21+ years (data not shown), but stronger among female subjects  than male subjects . There was no trend in risk with gestational age (P=0.63), and adjustment for gestational age did not change the OR for birth weight. Birth weight percentiles confirmed the increased risk among heavy babies . Longer birth length appeared protective though the association was not linear or statistically significant. The estimates for both birth weight and length were slightly stronger with mutual adjustment . There were no associations between risk and mother's primary job, smoking, and alcohol intake during pregnancy and father's smoking during pregnancy (data not shown).High birth weight was associated with an increased osteosarcoma risk  that wasOsteosarcoma appears to be positively associated with bone growth, based primarily on the rapid rise and fall of incidence rates from adolescence into young adulthood, and buttressed by the typical occurrence of this tumour (approximately 70% (vs 19.5–20.5 inches=0.59) , with other sites underrepresented, for example, skull, jaw, rib, and vertebral column. Because the hospitals are academic centres with a high rate of referral patients, the opportunity for referral bias exists. For this reason we stratified the controls to the distribution of cases according to hospital, and residential distance from the hospital. Risk estimates were virtually unchanged with adjustment for these variables, as well as for family income. The use of orthopaedic controls has potential disadvantages as well. If the factors we investigated are associated with risk for orthopaedic conditions as well as osteosarcoma, we might fail to identify differences. To mitigate this possibility we included a wide variety of diagnoses in the control group. Finally, the relatively small number of cases limited statistical power, however, owing to the rarity of this tumour, our study includes more cases than all but one of previously published studies (in-utero development. A more concerted effort to evaluate this aspect of aetiology is warranted.In conclusion, our results together with those of previous studies do not suggest a clear growth and development pattern that could explain the dramatic young-age peak of this malignancy. However, there are enough signals to speculate that growth and development characteristics may be markers of true aetiologic events to which they are weakly correlated. Given the sharpness of the young incidence peak, the most likely timing of these events is


The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth .st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age.Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 ± 4.1 ng/ml) than in SGA neonates  at birth, then similar at the 1During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status. Epidemiological studies have shown an association between a reduced size at birth and increased long-term risk for obesity, insulin resistance, type 2 diabetes, hypertension and cardiovascular disease in adulthood -3. Low bA role for adipose tissue in the pathophysiology of insulin resistance has been postulated in several studies . It is cIn adult humans, plasma adiponectin is an important insulin sensitizer, as its circulating level is inversely related to the body mass index and to measures of insulin resistance . Since fCirculating leptin concentrations, mainly produced by white adipose tissue, correlate with the development of foetal adipose tissue and later with the body mass index . The rolThe aim of the present study was to evaluate serum levels of leptin, adiponectin and insulin in infants born appropriate for gestational age (AGA) and small for gestational age (SGA) during the first year of life and to correlate these changes with auxological parameters.Thirty-three AGA   infants Neonates were randomly recruited at birth from the Neonatal Units of the Spedali Civili Hospital of Brescia and the San Matteo Hospital of Pavia, Italy.Subjects with evidence of malformations or genetic disorders were excluded from the study. Mid-parental height, used as an indicator of the genetic growth potential, was similar in AGA  and SGA groups (-0.12 ± 0.85 SDS).Among SGA infants, 16 were symmetrical and 13 asymmetrical. We defined "symmetrical SGA" neonates as having both birth length and weight less than 2 SDS corrected for gestational age and "asymmetrical SGA" neonates with birth weight only less than -2 SDS corrected for gestational age.The infants had similar diets, during the first year of life, they received only milk until the fourth month, then one solid meal was introduced at the sixth month and two solid meals at the eighth month.2 (m2) [In all infants, weight, length and head circumference were evaluated at the second day of life, and at one, six and 12 months by a trained paediatrician, and converted to SDS to adjust for age and sex ,21. The nd day of life and did not use cord blood in which hormone levels may derive from the maternal circulation or from other maternal tissues, such as the placenta [At regularly scheduled control visit, a blood sample was obtained from each neonate (in the fasting state) for the determination of glucose, insulin, adiponectin and leptin. In order to avoid possible confounders in assessing hormone levels at birth, we took blood samples from the neonates on the 2placenta ,23.The study protocol was approved by the local Ethics Committee. The study's purpose was fully explained to each pregnant woman and written informed consent was obtained before enrolment.Glucose was measured immediately using a commercial glucometer . Blood samples were then centrifuged and serum was frozen at -20°C until the measurements were performed.Serum adiponectin and leptin concentrations were measured by a commercially available ELISA assay . The minimum detectable concentration for adiponectin was 375 pg/ml and the intra- and inter-assay coefficient of variation ranges were 3.2-7.3% and 4.6-5.8% for a quality control range of 0.7-2.9 ng/ml, respectively. The minimum detectable concentration for leptin was 15.6 pg/ml and the intra- and inter-assay coefficient of variation ranges were 3.2-3.3% and 3.5-5.4% for a quality control range of 65-600 ng/ml, respectively.Serum insulin levels were measured by an automatic chemiluminescent assay ADVIA centaur IRI . The minimum concentration detectable by this assay is 0.1 μU/ml. The intra- and inter-assay coefficients of variation were 2.1-5.0% and 4.2-6.3% for a quality control range of 0.6-4.0 μU/ml, respectively.Insulin resistance was estimated with fasting insulin and glucose levels using the homeostasis model assessment insulin resistance index (HOMA-IR), using the following formula: fasting serum insulin (μU/ml) × fasting plasma glucose (mmol/L)/22.5.Although the HOMA-IR measure is less accurate than the euglycemic clamp method used in large epidemiological studies, it is a reasonable alternative to the complicated clamp method that requires continuous intravenous administration of insulin and glucose for 3 h to calculate insulin sensitivity . A HOMA-Even if the gold standard techniques for measuring insulin sensitivity in children are Bergman's minimal model and the hyperinsulinaemic-euglycemic clamp ,27, the 2PO4/0.15 M NaCl/0.02% NaN3 elution buffer. One minute fractions, eluted with 0.8 ml/min flow rate, were analysed for adiponectin content with the ELISA assay.Samples of 250 μl of pooled serum were gel-filtered on HyPrep 16/60 Sephacryl-S-200 High Resolution columns equilibrated with 0.05 M NaHData were analysed using the statistical analysis software package Statistica 7.0 (Stasoft Inc). Descriptive statistics were calculated and reported as the mean and standard deviation. Non parametric tests were used for statistical analysis. The Mann-Whitney U test for unpaired samples was used to compare anthropometrical and laboratory parameters between SGA and AGA infants, at each time point of the study. The non-parametric Wilcoxon test for paired samples was used to compare anthropometrical and laboratory parameters at different times. Correlations were analysed using the Spearman rank correlation test. A p value < 0.05 was considered statistically significant.As shown in table As shown in figure In order to investigate whether SGA and AGA subjects show a different distribution of the isomers for adiponectin, we fractioned adiponectin pooled serum samples into the three major molecular fractions, using a validated fast protein liquid chromatography assay. As shown in figure No statistically significant correlations were found between adiponectin levels and auxological parameters at any time point, in any neonate.No statistically significant difference in adiponectin levels was shown between symmetrical and asymmetrical SGA infants at birth and during the first year of life table . A signith and 12th month of age, leptin returned to a comparable level between the two groups, even if at the latter time point SGA levels were slightly higher than AGA values, the difference was not significant.As shown in figure A comparison of leptin levels for asymmetrical and symmetrical SGA infants, did not reveal any statistically significant difference at any time during the study table . In bothLeptin concentrations at birth were positively correlated with the BMI , birth head circumference  and insulin levels  in all the infants. After birth, a positive correlation between leptin levels and BMI at six months was found  in all neonates and also for AGA and SGA subjects separately.As shown in figure Insulin concentrations for symmetrical and asymmetrical SGA infants were not statistically different at any study time point table , althougInsulin concentrations at one year of age positively correlated with the BMI  and head circumference  in all the infants. No other correlations were found at the other time points.In order to evaluate insulin resistance in AGA and SGA subjects during the first year of life, we calculated the HOMA-IR index. Like insulin levels, the HOMA-IR index was comparable between AGA and SGA infants at birth and at all study time points (data not shown). The HOMA-IR index was lower at birth in both groups (p < 0.01) and then increased from the first month to 12 months of age, remaining in the normal range .The HOMA-IR index was also comparable between asymmetric and symmetric SGA infants at all time points.To further verify the relationship between changes in height SDS and BMI SDS with those of adiponectin, leptin and insulin, we calculated the delta between birth and the first year of life for each parameter and the relationship between each parameter pair (data not shown). We did not observe any significant correlations.This study presents longitudinal data, from birth to one year of age, on anthropometrical development and serum adiponectin, leptin and insulin levels in a cohort of AGA and SGA infants, including both symmetrical and asymmetrical neonates.To the best of our knowledge, adiponectin and leptin studies at birth have always been performed on cord blood, which is not considered the ideal material for evaluating these growth stimulating-factors. As we previously indicated, cord blood may present confounding factors -25,33. OThe relationship between adiponectin and foetal growth has been poorly investigated. Some authors have found a positive association between cord blood adiponectin levels and birth-weight ,34, whilFurthermore, adiponectin levels do not correlate with birth weight and the physiological relationship with adiposity, observed in adults, is absent at birth.We found that adiponectin levels in both AGA and SGA neonates were higher than those found in healthy adults in other studies . This isWe have also evaluated adiponectin fractions with different molecular weights in SGA and AGA neonates, in order to verify if there was a peculiar distribution of adiponectin isomers. We found a similar chromatographic pattern of adiponectin fractions in AGA and SGA subjects, during the first year of life, confirming the absence of modifications in total circulating adiponectin. Furthermore, in other recent studies by Ibanez et al. ,42, the Interestingly, in this study we found leptin levels to be higher in AGA neonates with respect to SGA infants at birth, in accordance with recent studies . On the Leptin levels of all the neonates at birth were positively correlated with the BMI and head circumference. This may reflect either a simple relationship with adipose tissue or an active role for leptin in foetal growth, since it is known that leptin plays a role in the development of both the foetus and neonate, influencing also head circumference.In our report we demonstrated comparable insulin levels and HOMA-IR indices between AGA and SGA infants at birth and at 1, 6 and 12 months of age. Only at birth, were levels of insulin in SGA neonates lower than in AGA infants, but the difference was not statistically significant, probably due to the relatively low number of subjects enrolled in the study. However, insulin levels and HOMA-IR index still remained in the normal range in SGA subjects during the first year of age, suggesting that no insulin resistance develops during this period and that insulin alone does not explain changes in adiponectin levels.The discrepancies between our results and those showing different insulin levels at birth between AGA and SGA infants and a relationship between birth weight with insulin resistance -47 couldIn conclusion, minor changes in serum adiponectin, leptin and insulin levels can be observed in AGA and SGA infants during the first year of life. In particular, a progressive decrease in adiponectin levels is observed, while leptin values change according to nutritional status. In fact, leptin levels in all neonates either at birth or at 6 months positively correlated with the BMI (p < 0.05), confirming that leptin is involved in the regulation of body weight and that its plasma level reflects fat reserves.The authors declare that they have no competing interests.EB and AG participated in the design of the study, collection of data and helped to draft the manuscript. CM analysed and interpreted the data, performed the statistical analysis and drafted the manuscript. MA carried out the chromatographic analysis. PT performed the immunoassays. SP was involved in drafting and critically revising the manuscript. MB coordinated the study and helped to draft the manuscript. All the authors have read and approved the final manuscript.


The safe delivery process conducted in an institution will have a definite impact of reduction of maternal mortality. Delivery of a newborn in an Institution also provides an opportunity to the health care system to administer at birth immunization. Immunization of a newborn with BCG vaccine enhances the efficacy of the vaccine by avoiding the interference with atypical mycobacterium which can infect the child during the post neonatal period.Likewise, administration of “0 dose” of OPV leads to early colonization of the intestinal tract with the attenuated vaccine virus which can act as a barrier to the wild polio virus. At birthThe present study was undertaken with the following objectives: a) To study the pattern of ‘at birth’ immunization after the implementation of JSY. b) To compare it with the status of previous year before implementation of JSY. c) To study the perception of parents regarding ‘at birth’ immunization.st April 2007 to 30th September 2007 in the Epidemiology out-patient department (OPD) of Department of Community Medicine, MKCG Medical College Hospital, Brahmapur, Orissa. The JSY scheme was implemented in this tertiary level health care center from 12th May 2006, but the operationalization of the scheme came into effect from the month of Dec 2006. As the financial year of the government starts from 1st Apr of every year, the comparison of ‘at birth’ immunization were from 1st Apr 2006 to 30th Sep 2006 as pre JSY scheme and between the same period of the year 2007 i.e. 1st Apr to 30th Sep 2007 as the period of JSY scheme operationalization. The data on those periods were collected by record-survey from the register of the immunization clinic. The parents were also interviewed for perception regarding at birth immunization and the data were analyzed in the Department of Community Medicine, MKCG Medical College Hospital.The study was cross-sectional one and the data was collected by a pre-designed schedule from the parents of all the babies attending the immunization clinic for BCG and ‘0’dose OPV immunization from 1st April to 30th September 2006, the total no of ‘at birth’ immunization carried out was 397 (out of the 1699 babies attended for immunization) with a median average monthly administration of 54. After the implementation of JSY Scheme in this Medical College Hospital, the total number of ‘at birth’ immunization carried out in the same months of 2007 was 870 (out of the 2332 babies attended for immunization) with a median average monthly administration of 153 [The study revealed that during 1n of 153 .In 2007 out of the 870 immunized babies 468 (53.8%) were male and 402 (46.2%) were female and regarding their residential status 32% were from urban and 68% were from rural area, where as in 2006 the male babies attended for immunization were 237 (59.7%) and female babies were 160 (40.3%) and their residential status are 45.8% from urban and 54.2% from rural area. The total number of deliveries in the Hospital during April-Sept 2006 was 714 and at birth immunization given was 397 i.e. 55.6% of the newborns turned out for at birth immunization, whereas in 2007 during the same period 870 new borns out of 920 were immunized at birth i.e. about 94.5%, which showed a drastic increase of at birth immunization.P < 0.001) [In 2007, a total of 769 (88.4%) babies attended the immunization clinic within 7 days of birth where as in 2006 during the same period, a total of 206 (51.9%) babies attended within 7 days of birth for ‘at birth’ immunization. The difference in number of at birth immunization in pre and post JSY period was found to be highly significant (< 0.001) .Regarding perception of parents on ‘at birth’ immunization, 49.4% parents from urban and 56.2% parents from rural area knew about it from ASHA, 14.3% parents from urban and 28.4% parents from rural area were knew it from Health Worker Female/Anganwadi Worker. 25.1% parents from urban and only 8.8% parents from rural area were self-aware regarding at birth immunization .642 (73.8%) parents knew that BCG is given at birth and 791 (90.91%) knew that OPV is given at birth, but only 230 (26.43%) and 654 (75.17%) parents knew that these vaccines prevent tuberculosis and polio, respectively .P < 0.001) after implementation of JSY. It may be due to rise in institutional deliveries which are motivated by the monetary incentive given to the mother. At birth immunization during early neonatal period is increased significantly from 51.9 to 88.4% as mostly ASHA's accompany the mother and ASHA gets her incentive after immunizing the child. Similar studies done in Afghanistan by A. Hadi et al. reveals that institutional deliveries increases where there is intensive community mobilization, provision of free services, transport facilities at night, incentive to health providers and quality of services which are the key factors for rise in institutional delivery.(The ‘at birth’ immunization from April to September from 2006 to 2007 increased significantly (The total number of deliveries in the hospital during April-Sept 2006 to 2007 increased from 714 to 920 and the increase in at birth immunization was seen from 55.6 to 94.5%, which showed a dramatic increase. A similar study was conducted at Bongaigaon district and the institutional deliveries conducted during the period of April to August 2006 were 601, whereas during the same period in 2007 it was 1524.(Most cases are from rural areas as it is a tertiary level health care; the patients from nearby areas are referred to this hospital. ASHA's do work of community mobilization and motivation. Similar studies by Huang J and Tembo KC have found that provision of services alone can not raise the need and utilization of services unless there is motivation.7After the implementation of JSY scheme, ASHA's have been successful in promoting institutional deliveries. Family members and mothers are convinced to go for institutional deliveries, so effective promotion among pregnant women and their family members played a role for rise in institutional deliveries.One-fourth of the parents from urban area were self-aware regarding at birth immunization, which was very low among rural parents. This may be due to literacy level. In states like Tamil Nadu and Kerala awareness about maternal health issue is high and citizens demand more. Literacy also plays a key role in rendering maternal health services.Though the number is less, it is very encouraging that some parents knew about Hepatitis-B vaccination during ‘at birth’ immunization.JSY has significant impact on institutional delivery and Accredited social health activist/Anganwadi worker are the main motivator for ‘at birth’ immunization.Monetary benefit of ASHA is the main factor which brings people for at birth immunization, not the vaccines which prevent the disease. Therefore, steps to create social mobilization among the community to avail not only the benefits but also on the objective of JSY should be immediately taken up.The thrust of the NRHM was to establish a fully functional, community owned, decentralized health delivery system. The implementation of JSY scheme will surely have an impact on indicators like MMR, IMR due to the rise of institutional delivery.The innovative engagement of human resources as per need and the arrangements for incentives at each level will help to build up a role model of public health delivery system.


The incidence of primary papillary carcinoma arising in thyroglossal cyst is rare and occurs in <1% of thyroglossal cysts. Even rarer is its diagnosis by pre-operative fine needle aspiration cytology (FNAC). Only 15 such cases diagnosed by FNAC have been previously reported in the literature. In this article, cytomorphology of the current case is presented along with a review of the literature on FNAC and its diagnostic pitfalls. Thyroglossal duct cyst is the most common nonodontogenic cyst of the adult population, presenting as midline neck swellings. The incidence of papillary carcinoma arising in the thyroglossal duct cyst is rare <1%). Approximately 150 cases of papillary carcinoma arising in the thyroglossal duct cyst have previously been reported in the literature.%. Approx There ar1A 22-year-old asymptomatic female presented to the surgical outpatient department with a history of midline neck swelling of two years duration. There was no history of prior radiation. On examination, a well-circumscribed, painless, firm, fluctuant, 2 × 2 cm mass in the midline of the neck at the level of the hyoid was found. It showed vertical movement on deglutition. A clinical diagnosis of solitary thyroid nodule was made. There was also right submandibular lymph node enlargement (approx 1.5 cm in diameter). The patient was subsequently referred for FNAC.Giemsa and PAP-stained highly cellular FNAC smears were composed of big papillary clusters having a fibrovascular core  and few Hence, preoperative diagnosis of thyroglossal cyst was made and Sistrunk’s operation was performed.The cyst was resected and sent for histopathological examination. Gross examination showed a small cystic mass measuring 2 × 1 cm, with an attached part of hyoid bone and skeletal muscle. Cut-section of the cyst showed multiple small friable papillary projections filling the entire cyst. Microscopically, the cyst showed multiple branching papillae with a thin fibrovascular core projecting into its lumen . The papThyroglossal duct cyst is the most common nonodontogenic cyst, prevalence being 7% of the adult population. CarcinomIncidence of papillary carcinoma arising in the thyroglossal duct cyst is <1%, and it is usually seen in younger women, with a sex ratio of 1.5:1.1 This patLiterature reveals 15 cases of preoperative FNAC of the thyroglossal duct cysts with papillary carcinoma . Nine of17816The cytomorphological features on FNAC have been described by few authors. Some considered diagnosis of papillary thyroid carcinoma on the basis of papillary fragments, while others also described intranuclear pseudoinclusions and multinucleated giant cells.–712 The 7813Although diagnostic criteria of papillary carcinoma thyroid and thyroglossal duct cyst on FNAC have been defined, diagnostic pitfalls in giving accurate diagnosis of papillary carcinomas arising in the thyroglossal duct cyst are very common. Major criteria are high cellularity, papillary formations, cells with enlarged nuclei showing anisonucleosis and powdery chromatin and definite nucleoli. Intranuclear pseudoinclusions and grooves are significant. Psammoma bodies, multinucleate giant cells and ropy colloid are variably present.FNAC yielded correct results in only 50–66% of cases.14 The faAnother pitfall in the diagnosis is locating the origin of the tumor by cytological testing alone. In cases of solitary thyroid nodule, entity of the thyroglossal cyst must also be kept in mind and on finding malignancy on FNAC, CT scan or ultrasound should be advised to decide the origin. This can prevent thyroidectomy and its complications.FNAC also lacks in finding cyst wall infiltration by tumor cells. It is important to quote cyst wall infiltration in the diagnosis as the treatment and prognosis depend on this. If the cancer has not invaded beyond the cyst wall, simple complete excision of the cyst using the Sistrunk’s procedure is adequate. If the cHence, location of the target lesion, careful searching for malignant cells and repeat FNAC are the key to successful diagnosis. Prognosis of papillary carcinomas is good, whether it occurs in the thyroglossal duct cyst or in the thyroid proper, but frequency of lymph node metastasis is lower in papillary carcinomas arising in the thyroglossal duct cyst than that arising in the thyroid proper.This case is reported in view of the rarity of pre-operative FNAC diagnosis of this entity and to highlight the diagnostic pitfalls and importance of FNAC to plan a proper surgical management.