The incidence of preterm birth in developed countries has risen in the past decades. Underlying causes for this enigmatic pregnancy complication are numerous, yet infectious agents that induce dysregualtion of immunity at the maternal-fetal interface pose one of the most probable causes of preterm birth. This paper highlights two factors regarding maternal infections that trigger unscheduled inflammatory sequences that are deleterious to the maternal-fetal balance necessary to maintain pregnancy. Firstly, we discuss the role of Toll-like receptors (TLRs) as sentinels of uterine immunity in the context of response to pathogens. We highlight the idea that particular TLR activations lead to differential immune cascades that induce preterm birth. Secondly, two alternative routes of pathogenic entry may prove to be critical for inducing preterm birth via a cytokine storm or a secondary and currently unknown cell-mediated mechanism of uterine inflammation. This paper summarizes pathways that underlie activation of adverse and diverse immune responses to foreign agents that may result in preterm birth. Healthy pregnancy is the result of a tightly regulated system of crosstalk between maternal and fetal structures. Implantation and parturition are specifically characterized by states of inflammation , 2. ProiPreterm birth can result from a range of causes such as exposure to environmental triggers, maternal stress, fetal or maternal genetic abnormalities, or hormonal imbalance. However, infection is one of the most heralded causes of preterm birth due to the drastic link between underlying infectious agents and their ability to promote inflammatory responses –8. It isInvestigation into the mechanisms that lead to preterm birth in response to pathogenic agents should take into account several key factors. Firstly, the route of entry that a given foreign agent takes determines where the agent will ultimately subsist and what pathways will be activated. Recent evidence demonstrates that the same pathogen, delivered through alternative routes, can lead to differential inflammatory responses , dendritic cells, T regulatory cells (Treg), and macrophages. uNK cells are the most thoroughly studied uterine immune cells due to lack of their natural cytotoxicity, an alternative receptor repertoire to peripheral blood counterparts, and the ability to produce vascular growth factors, cytokines, and chemokines during early stages of pregnancy , 22. In α , 14. Thuα, IL-10, and TGF-β throughout placentation [α and MCP-1 to signal the further invasion of macrophages for phagocytosis [While uNK cells do not play a documented role in term birth, macrophages may hold the key to conduction of proper parturition. Uterine macrophages are found in proportions upwards of 20% of the total uterine lymphocyte population. Over the course of pregnancy, uterine macrophages are present as innate immune sentinels due to their expression of TLRs. However, macrophages are immunomodulatory over the course of gestation as they simultaneously produce TNF-entation . Along socytosis –30. Repoocytosis .α, IL-12, and IL-10 [The function and phenotype of dendritic cells in the uterus is beginning to be expounded upon. Recent studies have highlighted their role in crosstalk with uNK cells and trophoblasts in order to orchestrate production of cytokines such as TNF-nd IL-10 . While tnd IL-10 . Thus, w−/− mice given the TLR4 agonist LPS deliver preterm. Infusion of Tregs into these mice rescues pregnancy to term, indicating an advantageous role for these cells in TLR-pathogen mediated response to adverse pregnancy outcomes [While uNK cells, macrophages, and dendritic cells aid to orchestrate the balance between pro- and anti-inflammatory milieu over the course of gestation, T regulatory cells Tregs in the uterus are thought to be mainly immunosuppressive. Studies demonstrate the importance of these cells as adoptive transfer of Tregs into abortion prone mice leads to pregnancy rescue . T-cell-outcomes . The fun‒/‒ mice show high levels of macrophage and neutrophil infiltration in the pregnant uterus [While the aforementioned cellular activities are highly orchestrated throughout pregnancy and particularly during the onset of labor, these actions are correlated to specific hormonal cues that allow for these changes. For the majority of pregnancies one of the main mechanisms that allows for uterine quiescence and lack of uterine muscle movement is the increased presence of the hormone progesterone , 37. FemκB activity that allows for production of inflammatory cytokines and mediation of progesterone withdrawal through modulation of the participation of different PRs [How does the presence of viral or bacterial organisms lead to preterm birth? It is rarely the foreign organism itself that causes preterm birth. Rather, it is the immune response of the host evoked by the pathogen that leads to aberrant pregnancy outcomes. With the knowledge of parturition as a process mediated by inflammation, we can begin to understand that pathogenic insults can trigger unscheduled uterine immunity. Evidence demonstrates that the activated TLR pathways and the route of pathogenic entry may determine the immunological cascade of aberrant cellular and cytokine activity that lead to preterm birth , inflammatory cytokines IL-1staining –50. Furtstaining , 51.Though data is relatively scarce, evidence suggests that viral entry into trophoblast cells induces trophoblast apoptosis and the resultant inflammatory events can lead to preterm birth . The genHere, we summarize known pathogens, viral or bacterial, associated with induction of preterm birth. We highlight immunological pathways that demonstrate specific PAMPs that activate TLRs to induce preterm birth. Work in mouse models illustrates differential TLR-mediated cascades of inflammatory-based uterine immunity that can lead to preterm birth. Importantly, clinical correlates where amniotic fluid is tested or maternal/fetal membranes are probed begin to support these findings.κB transcription factor, and first trimester trophoblasts produce significant amounts of IL-8 and IL-6 ultimately undergoing apoptosis [α production or NF-κB activation [TLR2 is one of the more promiscuous TLRs in that upon activation it can concomitantly signal with TLR1 and TLR6. In line with these findings, TLR2 is not only specific for gram positive bacteria due to its specificity for peptidoglycan, but also signals upon recognition of meningococcal porins, fungal, parasitic, and viral pathogen-associated molecular patterns . Studiespoptosis . In conttivation   [Ureaplasma ureaticulum is one of three bacteria that are grouped together and termed bacterial vaginosis. While common genital infections such as Chlamydia trachomatis and neisseria gonorrhoea are rarely associated with aberrant pregnancy outcomes, high loads of bacterial vaginosis in pregnant women prove nine times more likely to lead to prematurity [ureaplasma ureaticulum is an important correlation in the literature to follow at the clinical level. CMV shows the greatest correlation of human infection and adverse pregnancy outcomes as this herpes virus is present in 80% of the general population, but becomes active under conditions of immune suppression. Data demonstrate that human CMV may infect syncitiotrophobalsts or cytotrophoblasts and induce proinflammatory cascades such as IL-8 production [TLR2-specific human pathogens that correlate with increased incidence of preterm birth are us (CMV) , 56. Urematurity . Thus, toduction , 58.While TLR2 generally “sees” pathogens that are extracellular, TLR3 possesses specificity for double stranded RNA viral motifs and is found in endosomal pockets. Recently, it was shown that TLR3 can recognize products of cellular necrosis, a fact of importance for a system such as pregnancy where cellular turnover is abundant . EvidencκB pathway was activated leading to downstream cascades of inflammatory signals. Studies have utilized poly(I:C) as well to assess the role of preterm birth through TLR3 activation in mouse models. Where poly(I:C) was injected intraperitoneally to mimic a maternal systemic infection, mice gave preterm birth through an NK-κB-dependent mechanism and demonstrated marked serum and placental production of IL-6, IL-12, and MCP-1 [α-mediated axis. In contrast, in a model of intrauterine infusion, INF-β  and CCL5 were the major contributors to preterm birth outcomes in response to poly(I:c) and TNF-α production was not significant [Trophoblasts express the coxsackievirus and adenovirus receptor (CAR). Upon adenoviral infection, trophoblasts underwent apoptosis and this led to recruitment of a decidual immune response . Studiesnd MCP-1 , 60. Ournificant . Taken tmycoplasma hominis and trachtomonas vaginalis, are gram negative and thus have the capacity to signal via TLR4 [E. coli cause increased uNK cell cytotoxicity and TNF-α production, ultimately leading to preterm birth. Neutralization of TNF-α  or abolition of uNK cells rescued pregnancy to term. In contrast, our unpublished model of E. coli intrauterine infusion demonstrates that preterm birth does occur, but not in a TNF-α-dependent manner , a viral mimic. Importantly, other reports show that systemic injection of poly(I:C) induces trophoblast apoptosis after a vigorous cytokine storm lending to a preterm birth outcome. Taken together, these two reports are not disparate. Finally, in the context of TLR9 activation it has been shown that macrophages and neutrophils infiltrate the placental zone and lead to preterm birth or intrauterine fetal death outcomes. In regards to activation of specific TLRs, systemic injection of different PAMPs demonstrates that alternative immune cell subsets respond based on the pathogen at play. Bacterial pathogens signaling through TLR2 or TLR4 show strong staining within human chorion and amnion membranes. Murine studies emphasize the role of uNK cell amplification and TNF-As a whole, the reports discussed in this paper lend strong evidence to the postulate that the pathway to induction of preterm birth is dependent on the TLR activated—a product of the type of pathogenic infection. Secondly, the route of entry, intrauterine ascension versus systemic infection, plays a role in determining the cytokine profile activated and the ensuing mechanism of fetal rejection. From a clinical standpoint, it may be paramount to account for not only the type of infectious agent at play within the maternal-fetal system, but also the route through which the pregnancy was compromised.


Preterm birth is a complex disease with etiologic influences from a variety of social, environmental, hormonal, genetic, and other factors. The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate.Population-based study utilizing Missouri's birth certificate database (1989–1997). We conducted a multilevel logistic regression analysis to estimate the effect of county-level poverty on PTB risk. Of 634,994 births nested within 115 counties in Missouri, two levels were considered. Individual-level variables included demographics factors, prenatal care, health-related behavioral risk factors, and medical risk factors. The area-level variable included the percentage of the population within each county living below the poverty line . Counties were divided into quartiles of poverty; the first quartile (lowest rate of poverty) was the reference group.th quartile (4.9%), p < 0.0001. High county-level poverty was significantly associated with PTB risk. PTB risk (< 35 weeks) was increased for women who resided in counties within the highest quartile of poverty, adjusted odds ratio (adjOR) 1.18 , with a similar effect at earlier gestational ages (< 32 weeks), adjOR 1.27 .PTB < 35 weeks occurred in 24,490 pregnancies (3.9%). The rate of PTB < 35 weeks was 2.8% in counties within the lowest quartile of poverty and increased through the 4Women residing in socioeconomically deprived areas are at increased risk of preterm birth, above other underlying risk factors. Although the risk increase is modest, it affects a large number of pregnancies. Preterm birth is a major public health burden whose prevalence continues to rise. The rate of preterm birth in the U.S. is 12.7%, the highest rate reported to date. Our limIt has been hypothesized that the association between preterm parturition and individual-level socioeconomic deprivation is primarily accounted for by the co-existence of other significant risk factors such as medical comorbidities, lack of prenatal care, and adverse behaviors  which occur more commonly in women of lower socioeconomic status. HoweverImplementation of appropriate statistical methodologies, rigorous adherance to study design, and consideration of as many clinically important covariates as possible optimizes the capability to accurately quantify the independent association between area-level poverty and preterm birth risk. When taking into consideration that people who reside within the same area share common area-level neighborhood conditions, individual-based statistical models such as traditional logistic regression analyses are not optimal to determine the true strength of the association. Using multilevel logistic regression analysis has the advantage of allowing one to estimate not only the fixed effects of individual-level and area-level factors, but also the random effect of geographic variation of preterm birth between areas.The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate.A data set which included Missouri birth records from 1978–1998 was provided in a de-identified fashion for this analysis by the Missouri Department of Health and Senior Services. The study was considered exempt from review by the Missouri Department of Health and Senior Services IRB and the Human Subjects Committee of Washington University in St. Louis. This data set has been a rich source for the analysis of factors associated with birth timing -10.A total of 1,577,082 births occurred in Missouri between 1978 and 1998. To optimize our capability to examine the influence of important individual factors, we limited our study to those births which occurred between 1989 and 1998 due to an unacceptable amount of missing demographic data for births that occurred before 1989 due to revisions in the birth certificate format in 1989 and improvements in edit and query systems after that date. Because deliveries which occur prior to 20 completed weeks of pregnancy are considered miscarriages rather than births, we limited our analysis to births recorded as having occurred at 20 weeks or greater. We excluded births resulting from a multifetal gestation, intrauterine fetal demise, or involving a major congenital malformation due to their know propensity to deliver preterm, potentially for mechanisms unrelated to the exposure we wished to evaluate. After these exclusions, the study population consisted of 675,044 births. We further limited our analysis to births occuring to mothers whose reported residence at the time of delivery was in the state of Missouri. There were 40,050 births in Missouri to mothers who resided in other states during the study period, yeilding a final population of 634,994 births available for analysis.Preterm birth, as defined by the World Health Organization, is a delWe included the following individual-level measures: maternal age, maternal race (self-reported), maternal and paternal highest educational attainment, residence within city limits, birth sequence, marital status, presence of medical risk factors, marital status, indicators of low income , adequacy of prenatal care received, health-related behaviors , and presence of medical risk factors. Individual-level risk factors were selected from the data set based on clinical relevance and association with preterm birth.Maternal and paternal education levels are recorded in the database in years of education completed, which we dichotomized as educational levels of < 12 years versus 12 years or more in order to identify those with less than a high school education. The variable of maternal education had minimal missing data, and paternal education was less complete with 22.6% missing data. A composite dichotomous variable of low socioeconomic status was created from the individual dichotomous variables of recipient of any of three state funded support programs . A dichotomous variable of inadequate prenatal care was created from a continuous variable which indicated the month of pregnancy when prenatal care was initiated. Inadequate prenatal care was defined as having initiated prenatal care after 20 weeks of pregnancy, which is the latter half of pregnancy. A composite variable of heterogeneous medical risk factors indicated pregnancies complicated by anemia (hematocrit < 30% or hemoglobin < 10 gm/dL), maternal cardiac disease, acute or chronic lung disease, diabetes (insulin dependent), diabetes (other), genital herpes, hydramnios/oligohydramnios, hemoglobinopathy, chronic hypertension, pre-eclampsia, eclampsia, incompetent cervix, previous infant weighing > 4000 gm, previous preterm or small-for-gestational-age infant, maternal renal disease, Rh sensitization, or uterine bleeding.Poverty rate was obtained from US census data (1990) and was defined as the percentage of the population falling below the US federal poverty line at the county level of the mother's reported residence as a measure of area socioeconomic position. The poverty rate is a measure that is robust across various diseases and levels of geography; it has a link to possible policy implications, and is comparable over time,14. CounWe used multilevel logistic regression analysis to estimate the effect of county-level poverty on preterm birth risk. This analytic method can estimate not only fixed effects of individual-level and area-level covariates, but also the random effect of geographic variation of preterm birth across counties. When significant geographic variation exists, this indicates that preterm birth was not randomly distributed. The 634,994 births were nested within 115 counties in Missouri .Data were analyzed with SAS GLIMMIX macro . Findings with a p-value of < 0.05 were considered statistically significant.We calculated median odds ratios (MOR) and interval odds ratios (IOR),16 to esZ0.75 is the 75th percentile of standard normal distribution, VC is the variance of PTB between counties, and exp(·) is the exponential function[where  function. If the 80%-IORs were computed using the following equation:Z0.10 and Z0.90 are the values of the standard normal distribution at the 10th and 90th percentiles, respectively. β is the regression coefficient of each category of county-level poverty rate. Larger geographic variation results in a broader range of the IOR. If the IOR does not cross the value of one, it suggests that county-level poverty substantially contributed to the geographic heterogeneity of PTB.where The study population was comprised of 634,994 live births to mothers who resided in 115 counties in Missouri from 1989 – 1998 for an average of 5,522 births per county . The racial distribution of the study cohort was 82.4% White, 16.1% Black, 0.3% Indian, 0.5% Asian/Pacific Islander, 0.6% other/unknown.Table nd quartile: 3.4%, 3rd quartile: 3,9%, 4th quartile: 4.9%), p < 0.0001. Similarly, early preterm births (< 32 weeks) occurred more commonly in mothers who resided in counties with higher poverty rates. The rate of early preterm birth nearly doubled from 1.0% in the 1st quartile to 1.9% in the quartile with the highest poverty rate (p < 0.0001).The overall rate of preterm birth < 35 weeks for the entire study population was 3.9%. The rate of preterm birth < 35 weeks was 2.8% for mothers who resided in counties within the lowest quartile of poverty (Table st quartile), the risk of preterm birth < 35 weeks increased with increasing rates of county-level poverty in univariate analysis .When demographic factors are added to county-level poverty  was reduced to 1.0 when individual-level demographic factors were added to the model. The addition of other individual-level covariates such as prenatal care, behavioral risk factors, and medical risk factors only minimally influence the adjusted odds ratio (range 1.23 to 1.27).When considering preterm births that occurred at earlier gestational ages (< 32 weeks of gestation), the risk increase associated with high county-level poverty was similarly influenced by individual-level factors. The unadjusted risk of early preterm birth with high county-level poverty  demonstrated similar effect sizes when individual-level factors were added to the models Table . Many moThere was a modest amount of geographic heterogeneity of PTB across counties in Missouri as measured by MOR and IOR. In all multilevel models, MOR values ranged from 1.07 to 1.22, and IOR-80s ranged from 0.79 to 2.05. As some IOR ranges did not contain one, this suggests that county-level poverty was an important area-level characteristic for geographic heterogeneity of PTB. But, other unmeasured area-level chacteristics could have also contributed to this geographic outcome variation.In this study we found that women who gave birth in counties with the highest poverty rates were at increased risk of preterm birth at < 35 and < 32 weeks of gestation. Although these risks are modest, with odds ratio estimates of 1.18 and 1.27 respectively, the confidence intervals consistently excluded the value of one even after accounting for numerous individual demographic, obstetric, behavioral, and medical risk factors. These effects were similar regardless of maternal race. Modest increases in MOR and IOR values suggest that county-level poverty was an important area-level characteristic for geographic heterogeneity of PTB. But, other unmeasured area-level characteristics may also partly contribute to the geographic heterogeneity of preterm birth.Other investigators have reported an association of individual and area-level socioeconomic deprivation with adverse perinatal outcomes, such as low birth weight and preterm birth,17-26. AThe advantage of multilevel analytic approaches to health outcome research is that they enable us to evaluate and quantify the heterogeneity of the outcome across geographic areas. When minimal geographic heterogeneity exists, this implies high area-level correlation. When individuals within the population are similar and vary little with respect to health, this provides optimal conditions for regional prevention strategies. LikewisThe datasource used for this study has many advantages such as its large size and population-based nature. It includes a breadth of demographic information regarding the parents, detailed medical and obstetrical characteristics of the mother's antepartum and intrapartum course, as well as specific information regarding the status of the neonate at birth. Despite the extensive data available for analysis regarding each birth, there are some limitations to consider as well. One of the most commonly cited limitations of birth outcome research from vital statistics data is validity of the recorded gestational age. In an eAnother limitation of the study is the lack of ability to account for other county-level factors which could have possibly influenced the association between poverty and preterm birth risk, such as regional crime rates, adverse environmental exposures, etc. We incorporated as many clinically importanty concomitant factors into our analysis as were available through the data source, but we acknowledge that other unmeasured and unknown potential co-existant risk factors could potentially exist.In this study we chose counties as the geographic units of analysis. There are several reasons for this approach. US counties are the smallest geographical entity within a state with the social, political and legal responsibility for providing a broad range of social services and health care. Counties may qualify as communities to the extent that individuals and groups within them participate in community development by identifying county-wide problems, collecting health, social and environmental data, and by formulating and implementing specific public policy measures. CountieIn conclusion, county-level poverty was associated with an increased risk of preterm birth. Although the association is modest, even a modest increase in preterm birth risk as demonstrated in this study has the potential to have a robust effect given the large number of women residing in areas with relatively high poverty levels.Individual-level and area-level poverty have been associated in the past with an increased risk of preterm birth, but prior studies have been limited by design constraints and the inability to thoroughly account for potential confounding risks. We utilized a large population-based birth registry from the state of Missouri to perform a multi-level analysis of the association between poverty and preterm birth while accounting for many potential co-existent risks via optimal methodologic strategies. The findings from our study provide obstetrical care providers and health-care policy makers with important information regarding the prevalence of preterm birth in counties with high poverty and an accurate estimate of the effect of high area-level poverty on preterm birth risk.The authors declare that they have no competing interests.ED and LM developed the study hypothesis and along with MS contributed to the study design. ML and MS performed the data analysis and assisted the other coauthors with its interpretation. ED wrote the first draft of the manuscript. All authors contributed to revision and preparation of the final manuscript.The pre-publication history for this paper can be accessed here:


INSIG2 (insulin-induced gene 2) with obesity in multiple independent populations that include subjects ages 11–60 years.INSIG2 gene with obesity may change direction with age.Researchers have described the association of a common DNA polymorphism, rs7566605, near  Obesity is associated with multiple severe chronic illnesses such as cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, hypertension, stroke, and some forms of cancer.Recent studies have suggested that the rate of weight gain during infancy is important in the development of obesity.5INSIG2 gene. In a study of subjects ages 11 to 60 years, Herbert et al. found that the mean BMI of rs7566605 CC homozygotes under a recessive model was 0.60 kg/m2 higher than for GC or GG genotypes (p = 0.0008).INSIG2 is not associated with the risk for obesity, the finding of a positive association in five cohorts is unlikely a false positive finding.The single nucleotide polymorphism, rs7566605 is 10 kb upstream of the The objective of this exploratory study was to determine the extent to which an association exists between the polymorphism rs7566605 and gain in adiposity in the first 6 months and the first 3 years of life. We hypothesized that CC homozygosity would be associated with greater gain.Project Viva is a cohort study of pre- and perinatal factors related to outcomes of pregnancy and child health. Details of recruitment have been previously published.We compared the 319 Caucasian children in our study to the Caucasian children who were not included. We noted no material differences between the two groups for child’s gender, birthweight, gestational age, weight-for-length at birth, weight-for-height at age 3 years, maternal pre-pregnancy BMI, paternal BMI, maternal smoking during pregnancy, maternal age, or maternal history of gestational diabetes. The mean weight-for-length z-score at age 6 months of 0.62 [SD 0.99] for subjects in our study was smaller than for subjects who were not in our study .We obtained birth weight from the medical record. At ages 6 months and 3 years, study research assistants weighed the children with a digital scale , and measured length a few days after birth and at 6 months and height at 3 years using a Shorr measuring board .The research assistants collected additional demographic information on social, economic, maternal and paternal health information through self-administered questionnaires and interviews at study visits during pregnancy, post-delivery, and at the 6-month and age 3-year visits.Our main outcome measure was weight-for-length z-score, a marker of adiposity in this age group.23INSIG2 genetic variant rs7566605 with the TaqMan assay , and the genotyping completion rate was >95%, with less than 1% discordance.We genotyped the INSIG2 on weight–for-length at birth, 6 months, and 3 years, we used multivariate linear regression assuming a recessive model. Our final multivariate model included gender and candidate variables which confounded the main effect by >10%.We conducted analyses in SAS version 9.1 . In bivariate analyses, we evaluated each variable according to genotype. To estimate the effect of being CC homozygous for Genotype frequencies  were similar to the frequencies in other populations and consistent with Hardy-Weinberg equilibrium (p = 0.99).2 for GC or GG carriers). Subjects who were CC homozygous were more likely to have been born to a mother with a hypertensive disorder during pregnancy, including chronic hypertension, pre-eclamsia, or gestational hypertension (p = 0.02).The variant allele (C) frequency was 0.37. Subjects who were CC homozygous for rs7566605 did not differ from subjects who were GC or GG carriers for gestational age, gender, maternal education, or family income . ChildreAs shown in On multivariable linear regression, at age 6 months, subjects who were CC homozygous had weight-for-length z-scores that were 0.71 less  than GC and GG carriers when adjusting for gender, maternal pre-pregnancy BMI, weight-for-length at birth, maternal history of hypertensive disorder during pregnancy, and duration of breastfeeding in months . By age INSIG2 CC homozygosity is associated with smaller gain in weight-for-length between birth and age 6 months, but that by the age of 3 years no association is present. The finding of lower gain in adiposity during infancy associated with CC was contrary to our hypothesis. One possibility is chance. Our sample size was relatively small for a genetic association study, and our results will need to be validated in other cohorts. A second possibility is that low weight gain in infancy is a precursor to later obesity, and CC homozygosity underlies both. However, this possibility is unlikely because although one study suggests low infancy weight gain is associated with later coronary artery disease,Our exploratory study suggests INSIG2 gene in the first three years of life. Strengths of this study include accurate measures of length and weight, which is critical in studies of infancy.INSIG2 may be associated with maternal hypertensive disorders, and the presence of these disorders makes the mothers less likely to breastfeed. Since we did not genotype the mothers, these associations will need to be studied in other cohorts.This is the first study to examine the INSIG2 intronic polymorphism rs7566605. The effect of this gene on weight may change direction with age.In conclusion, gain in adiposity in the first six months of life may be influenced the


Nonparasitic splenic cysts are uncommon clinical entity and because of it, there is no information regarding their optimal surgical treatment.A 41-years-old female with incidentally diagnosed nonparasitic splenic cyst which initially was asymptomatic. After two years of follow up, the patient underwent surgery; subtotal cystectomy and omentoplasty as an additional procedure. Postoperative course was uneventful.Short and mid term results showed that near total cystectomy with omentoplasty was a safe successful procedure for treatment of epidermoid splenic cyst. There is confusion about the etiology, pathogenesis and classification of nonparasitic splenic cysts -7. The dThe aim of this presentation is to report the case of epidermoid splenic cyst treated with near total cyst resection with cyst wall edges plication and omentoplasty as an additional procedure, very rarely described in treatment of nonparasitic splenic cysts.echinococcosis, a laparoscopic cholecystectomy was performed, whereas the splenic cyst was followed-up. But, the mild pain on the left upper abdominal quadrant continuous to persist. Repeated abdominal US and CT after one respectively two years, have showed that the splenic cyst reached the size 6.0 × 5.0 cm and 7.4 × 7.3 respectively  concluded that plication of the cyst wall edges prevents the cyst walls from adhering and causing recurrence, as well as helping to control hemorrhage [Symptomatic nonparasitic splenic cysts are rare entity in clinical practice. There is confusion about their etiology, pathogenesis and classification as well -7. Morgee of 71% . In a remorrhage ,5,7,10.In our presenting case, through laparotomy was performed near total excision of the cyst along with a part of pericystic splenic tissue. Based on our long-term experience in treatment of hydatid cysts , the rem


To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools.A large scale candidate gene association study was performed on 1442 SNPs in 130 genes in a case (preterm birth < 36 weeks) control study (term birth > 37 weeks). Both maternal and fetal DNA from Caucasians (172 cases and 198 controls) and 279 African-Americans (82 cases and 197 controls) were used. A single locus association (genotypic) analysis followed by hierarchical clustering was performed, where clustering was based on p values for significant associations within each race. Using Ingenuity Pathway Analysis (IPA) software, known pathophysiologic pathways in both races were determined.From all SNPs entered into the analysis, the IPA mapped genes to specific disease functions. Gene variants in Caucasians were implicated in disease functions shared with other known disorders; specifically, dermatopathy, inflammation, and hematological disorders. This may reflect abnormal cervical ripening and decidual hemorrhage. In African-Americans inflammatory pathways were the most prevalent. In Caucasians, maternal gene variants showed the most prominent role in disease functions, whereas in African Americans it was fetal variants. The IPA software was used to generate molecular interaction maps that differed between races and also between maternal and fetal genetic variants.Differences at the genetic level revealed distinct disease functions and operational pathways in African Americans and Caucasians in spontaneous preterm birth. Differences in maternal and fetal contributions in pregnancy outcome are also different between African Americans and Caucasians. These results present a set of explicit testable hypotheses regarding genetic associations with preterm birth in African Americans and Caucasians Preterm birth (< 37 weeks of gestation) rates vary considerably between racial groups in the United States. The rate is 18.4% in non-Hispanic African-Americans and 11.7% in non-Hispanic Caucasians in 2005 , and genUnderstanding spontaneous preterm birth is difficult due to etiologic and pathophysiologic heterogeneities and racial disparity can further complicates this. Etiologic factors such as infection, stress, placental abruption, uterine distension, and preterm premature rupture of membranes, among others are associated with preterm birth in both races. Redundancy of biochemical pathways and biomarkers of preterm birth regardless of etiology suggests pathophysiologic heterogeneity. One explanation for racial disparity may be genetic variations (polymorphisms) that differ in frequency between races or that provide a different genetic context for particular polymorphisms to function. A review of the literature suggests emerging evidence for gene-gene interactions (epistasis) and gene-environment interactions in preterm birth -10, someIn addition to static genetic markers, dynamic biomarkers in amniotic fluid and fetal membranes also reveal significant racial disparity, such as inflammatory marker expression and their concentrations in preterm birth ,17. StudBased on the evidence generated in our laboratory on genetic  and biomarker data from African-Americans and Caucasians -17, we hThis study was approved by the institutional review board at TriStar, the parent company institutional review board of record for Centennial Women's Hospital, Nashville, Tennessee (USA).0/7 weeks gestation  followed by delivery. Cases and controls were selected from a Nashville cohort between September 2003 and December 2006. Subjects presented with preterm or term labor were given an opportunity to consent for the study when they matched our inclusion criteria. Subjects with medically indicated preterm births such as multiple gestations, preeclampsia, preterm premature rupture of the membranes, placental previa, infant anomalies, gestational diabetes, poly- and oligohydramnios, and other complications such as surgeries during pregnancies were excluded [0/7 weeks) with no medical or obstetrical complications during pregnancy.Genetic analysis performed on a case control study was used for this report. Mothers between the ages of 18 and 40 were recruited. Gestational age was determined by last menstrual period and corroborated by ultrasound dating. Cases (spontaneous preterm birth) were defined as presence of regular uterine contractions at < 36excluded -17. ContRace was identified by self-report and a questionnaire that traces ethnicity back two generations from the parents -17. IndiHigh-throughput candidate gene association studies were performed on 370 maternal (172 cases and 198 controls) and 319 fetal (140 cases and 179 controls) DNA samples from Caucasians and 279 maternal (82 cases and 197 controls) and 243 fetal (65 case and 183 control) samples from African-Americans. The candidate genes are listed in our earlier publications ,17. A to2 or Fisher's exact tests were used to test for differences in the counts of smokers and non-smokers, income differences, and insurance differences between cases and controls. STATA 9.0 statistical software was used for all analyses of clinical and demographic data and an uncorrected p value ≤ 0.05 was considered significant.Statistical tests for differences between case and control and African-American and Caucasian allele and genotype frequencies, measurements of allele frequencies and tests deviations from Hardy Weinberg Equilibrium (HWE) were calculated by the use of Powermarker statistical software . StatistTo examine whether the SNPs found to be putatively-associated with preterm birth in each race mapped to different biological networks and disease functions, we used IPA -26. The Disease function categories are among the biological functional ontologies developed by experts across broad domains of biology at IPA. There are 27 higher-order disease and disorder categories in the IPA knowledgebase, and below these higher order categories, there are lower level and specific functions. The IPA functional annotations have integrated GO data [We used the IPA software to identify new molecular network(s) that involve our focus genes. By drawing on its knowledgebase, the IPA software models cellular and molecular networks, including, binding, phosphorylation, proteolysis, nuclear receptor activation, gene transcription, and sub-cellular localization. We mapped focus genes to networks based on their mechanistic associations with each other and partner molecules. The IPA statistical algorithm identifies molecular pathways, involving these focus genes based on their selective interconnectivity with each other and additional molecules stored in the genome-scale knowledgebase. These networks are illustrated and ranked by the software for significance of focus gene enrichment.Demographic and clinical data and single locus associations with preterm birth pertaining to this data set has already been published ,14. BrieBecause the patterns of genetic association and therefore the detectable network patterns can be affected by differences in genotype and allele frequencies, it is important to assess the differences between our African-Americans and Caucasians prior to IPA analysis. After removing monomorphic markers and those with low genotyping efficiency from 1536 SNPs, 1442 remained for this analysis. Overall, the results indicate that the vast majority of SNPs assayed differed between African-Americans and Caucasians in genotype frequencies (~68–80%), and that controls appeared to be slightly more different than cases  than in Caucasian mothers (1.07E-7 to 1.90 E-4). Conversely, hematological "disorders", thrombosis, and hemorrhage  were significant in Caucasian mothers  but did not reach significance in African American mothers.While these analyses revealed disease functions assigned to our input genes, we were also interested in the functional biological networks employing these genes and proteins. Figures , 7, 8, 9Biological pathways leading to preterm birth are intertwined and redundant, and can involve inflammation, collagen remodeling, decidual vascular insufficiency, and myometrial contraction. Thus, parturition represents a tuned orchestration of regulatory loops. Therefore, in this study we examined the hypothesis that genetic variations in the molecules involved in these regulatory networks are important determinants of preterm birth. Our finding that preterm birth susceptibility genes mapped to multiple physiological functions including inflammatory diseases, dermatologic and connective tissue disorders (i.e. collagen metabolism disorders), hematological disease , and skeletal and muscular disorders  supports the role of multiple physiological processes in preterm birth Table , 3, 4. I2In this study molecular groupings generated by IPA suggest a new way of examining SNP data to predict events involved in preterm birth. The networks that were found to be most significant  by IPA can be viewed as modules of interacting molecules that act in key physiological compartments involved in the pathophysiology of preterm birth. For each network, the IPA analysis generated new potential interacting biomarkers (partner molecules) that are highly interconnected with the variant genes we tested and provide a set of new testable hypotheses regarding predisposition to preterm birth.Based on candidate gene studies, our group has already reported clear disparity in genetic associations with preterm birth in both maternal and fetal genome between African-Americans and Caucasians ,13,14. HThis systems biology approach enables the identification of new pathways and genes. Understanding these disease functions and molecular networking can help categorize women into specific risk groups for targeted intervention. This approach introduces few assumptions concerning the types of pathophysiological processes that might be discerned. Accordingly, some "disease functions" identified by IPA as being associated with preterm birth may not have an obvious connection with parturition or preterm birth. However, the strength of Ingenuity is its broad and unbiased coverage of peer reviewed literature in cell biology, organ physiology, and pathology. Thus, the literature in diverse fields may be used to reveal clues to preterm birth, and the disease functions, it can provide substantial insight as long as caution is used in interpreting the disease functions output from IPA. We also emphasize that the primary data on which these analyses are based is small and will also require follow-up studies.As with all studies connecting genetics, race, and PTB, our findings could be misused as an excuse for failing to rectify inequalities in social conditions and healthcare delivery that have well established links with PTB. However, genes act within environmental context, and we do not suggest race can be used as a proxy for genetic markers. For example, genes controlling inflammatory pathways are related to susceptibility to bacterial vaginosis, autoimmune disorders , and depIn conclusion, we performed a network analysis to identify molecules and risk pathways that were not explicitly tested in our original genetic studies. These analyses produced statistical and visual evidence of racial disparity in key networks associated with other disease phenotypes that can provide important insights into the pathophysiology of preterm birth.The authors declare that they have no competing interests.RM Conceptualized using bioinformatics tools to the genetic association data set, analysis and interpretation of analysis, drafted the manuscript. BP performed the ingenuity based data analysis and assisted manuscript preparation. DV performed genetic data analysis. SMW assisted and advised on genetic data analysis and assisted in manuscript preparation. MM assisted in concept development and manuscript preparation. SJF assisted in recruitment of subjects, provided clinical impact of data, assisted manuscript preparation. PT assisted in bringing the team to perform this study, analysis and assisted in manuscript preparation.


In a Danish nationwide cohort study of 292 births from 1973 to 2002 in women with Hodgkin's disease (HD), we compared birth outcome with 14 042 births from a cohort of mothers without cancer. We found no substantially increased risk of preterm birth, low birth weight at term, or stillbirth and no difference in proportion of male newborns for 192 children of women with HD before pregnancy. The prevalence odds ratio (POR) for congenital abnormalities was 1.7 : 0.9–3.1). Among 15 newborns of mothers diagnosed during pregnancy, the POR of preterm birth was 26.6 (95% CI: 8.5–83.0), but five out of the eight preterm deliveries among these women were elective. We found no substantially increased risk of adverse birth outcome among 85 newborns of women diagnosed within 2 years postpartum, though effect estimates were imprecise. The overall findings are reassuring, they cannot exclude the possibility of an increased risk of congenital abnormalities for newborns of women diagnosed with HD before pregnancy. Hodgkin's disease (HD) can affect women of childbearing age . AdvanceNevertheless, data concerning birth outcome in women with previous HD are sparse and consist mainly of case series .We examined the risk of adverse birth outcomes in a Danish nationwide cohort of women with HD before or during pregnancy, or within 2 years after delivery and compared them with those in a cohort of pregnant women without cancer.We used the Danish Cancer Registry, which has covered all incident cancers in Denmark since 1943, classified according to the International Classification of Diseases (ICD-7) , low birth weight at term <2500 g with ⩾37 completed weeks), stillbirth (delivery of a dead foetus at ⩾28 completed weeks of pregnancy), male proportion of newborns, and birth weight. The potential confounders included maternal age, parity, gestational age, and calendar period of the birth. For live-born children, data on congenital  abnormalities, diagnosed during the first year of life were collected from the National Hospital Discharge Registry, covering all hospital discharge diagnoses since 1977 and outpatient visits since 1995 (N=20 in the exposed and 698 in the comparison cohort).Birth weights ⩾7000 g probably reflected coding errors and were excluded, as were births with a gestational age below 20 or over 44 weeks. Owing to a coding change in the Birth Registry in 1978, there were more missing data on gestational age for the years 1978–1981 than for other years . Births without data on gestational age were excluded from the study . Group 2 included the births by women diagnosed with HD during pregnancy . Group 3 included births by women who were diagnosed with HD after delivery . If a woman gave birth more than once in this 2-year period, only the last birth before the HD diagnosis was included based on the assumption that the preclinical cancer would be more likely to affect the birth closest to the time of diagnosis.For all three groups, we computed the difference between proportions of male newborns of mothers with HD and comparison mothers.We computed prevalence odds ratios (PORs) as estimates of the relative risks with associated 95% confidence intervals (95% CIs) for preterm birth, low birth weight at term, stillbirth, and congenital abnormalities. The PORs were controlled for month and year of birth and county of mother's residence by matching. We used unconditional logistic regression analysis to further adjust for maternal age and parity. We also included the calendar period of the birth , as an independent variable in the model. Although there was no change in the risk estimates when calendar period of birth was included in the model, we kept the variable in the model. Stillborn children were excluded from the analyses of preterm birth, low birth weight at term, and congenital abnormalities.To examine whether sex of the child or maternal radiotherapy modified the POR estimates for births in group 1, we repeated the analyses in strata of boys and girls and strata of births of women who were treated with radiotherapy and women who were not. Furthermore, to examine whether calendar period of HD diagnosis modified the POR estimates for births in group 1, we repeated the analyses in different calendar periods of HD diagnosis (1981–1990 and 1991–2000), using 1970–1980 as reference. We used the Wald test to evaluate the homogeneity of the POR estimates for congenital abnormalities in 1981–1990 and 1991–2000. The low count of outcome events in groups 2 and 3 precluded stratified analyses.We used linear regression to estimate differences in mean birth weight, while controlling for maternal age, parity, gestational age, and calendar period of birth. Stillborn children were excluded from these analyses.The study was approved by the Danish Data Protection Agency (record no. 2003-41-2833). All analyses used SAS software, version 8.2. The SAS procedures used were PROC FREQ, PROC MEANS, PROC LOGISTIC, and PROC GLM.In total, we identified 292 singleton births delivered by women with HD and selected 14 042 singleton births for the comparison cohort. The characteristics of births in the three groups and their comparison births are shown in vs 50.1%  for group 2, and 61.2 vs 51.4%  for group 3.The prevalence of male newborns of women with HD in group 1 was 50.0%, compared with 51.3% among the matched comparison mothers . The corresponding findings were 73.3 P=0.25). Stratification according to sex of newborns did not substantially change the estimates (data not shown).The multiple linear regression analyses showed that newborns in all three groups had nearly the same mean birth weight as newborns in the comparison cohort (data not shown).This nationwide cohort study on the relation between maternal HD and adverse birth outcome did not show any increased risk of preterm birth or low birth weight at term, and no substantial increased risk of stillbirth in women with previous HD. However, we cannot rule out the possibility of a higher risk of congenital abnormalities for newborns of these women.The accuracy of our risk estimates depends on several factors. The main strength of the study is the underlying uniform health-care system, with complete registration of cancers and births and complete follow-up on congenital abnormalities diagnosed during the first year of life, allowing for a population-based design. Information on congenital abnormalities in the Hospital Discharge Registry is generally of high quality, with an 85% correct coding rate  from the Cancer Registry may be inaccurate, because they are not routinely validated. However, a study of childhood cancer survivors reported that 97 out of 110 patients treated with radiotherapy (88%), and 78 out of 79 patients not treated with radiotherapy (99%) were correctly coded in the Registry , or a few series of combination chemotherapy followed by radiation. In contrast, later stages of HD have typically been treated with six series of combination chemotherapy and only rarely radiotherapy. Thus, an uneven distribution of stage could have biased our results and may explain our finding of a lower risk of adverse birth outcomes for women treated with radiotherapy, compared with those who were not.Fetal abnormalities may lead both to miscarriage  and to iIt has been suggested that mutagenic exposure of germ cells  may decrease the proportion of male newborns in female survivors of cancer due to sex-linked lethal mutations . Our datWe believe that our study is the first to estimate relative risks for congenital abnormalities among newborns of women with HD. The increased risk estimates found after diagnoses during or shortly after pregnancy were imprecise. However, it is relevant that teratogens increase the rate of specific abnormalities but not all abnormalities , and we P=0.047). These three studies, however, were all based on small study population and did not control for potential confounders.Overall, our findings are in line with the existing studies. Two cohort studies found no substantial increased risk of low birth weight and no congenital abnormalities among newborns of 15 women with previous HD . There wRecently, a large cohort study of female survivors of childhood cancer found that 19.2% of 337 women with childhood HD had a preterm birth compared with 12.6% among sibling controls (The 26-fold increased risk of a preterm delivery for women diagnosed with HD during pregnancy reflected a higher rate of elective early delivery, probably to allow an early start of cancer therapy. This finding is consistent with another study on pregnant women with HD (The overall findings of this nationwide cohort study are reassuring, but we cannot rule out the possibility of an increased risk of congenital abnormalities in offspring of women diagnosed with HD before pregnancy.


The frequency of ovarian cysts in pregnancy is reported to be 1 in 1000 pregnancies. Laparoscopic ovarian cystectomy has been described in the literature as case series but this is the first case where an ovarian cyst at 20 weeks' gestation impacted in the pouch of Douglas was managed exclusively by laparoscopy.A 31-year-old primigravida woman was diagnosed as having an 11 cm ovarian cyst at 20 weeks' gestation. At the 19th week routine ultrasound scan, the mass appeared to be cystic with no solid component. She was asymptomatic. In view of the size of the cyst, options were discussed with her including laparoscopic ovarian cystectomy which she agreed to. Laparoscopic surgery during pregnancy is reported to be safe and beneficial for pregnant women. At laparoscopy, a transvaginal scan was performed to localize the cyst and an ovarian cystectomy was carried out. The patient had an uneventful recovery and subsequent antenatal period. She had a lower segment caesarean section for non-progress of labour when both ovaries were found to be normal and mobile.Laparoscopic surgery during pregnancy has numerous advantages compared to open laparotomy. This is a rare example of an ovarian cyst in the pouch of Douglas impacted behind the uterus which was managed by laparoscopy and shows the safety of the technique in the presence of an expert laparoscopic surgeon. The frequency of ovarian cysts in pregnancy is reported to be 1 in 1000 pregnancies. The authors present a patient with an ovarian cyst impacted in the pouch of Douglas at 20 weeks' gestation. It was managed by laparoscopic ovarian cystectomy.A 31-year-old Caucasian woman was booked into our hospital for her first pregnancy. An ultrasound scan at 19 weeks confirmed a normal fetal anatomy and a large simple septate cyst arising from the pelvis measuring 11 cm. Neither of the ovaries was seen, so it was difficult to determine the origin of the cyst. The cyst was not complex and was reported to be a simple cyst with a single thin septum. Although both ovaries were not visualized, which is not unusual at 19 weeks, because of the relationship of the cyst with the uterus and the cyst being in the pouch of Douglas, it was suggested to be of probable ovarian origin. The overall morphological features of the mass did not indicate malignancy. In view of the large size and septation of the cyst, the surgical option to remove the cyst by the laparoscopic technique was discussed with the patient, which she agreed to.2 to a pressure of 20 mmHg, a 5 mm cannula was placed through the same site. A 10 mm infra-umbilical port was inserted. Two secondary ports, 5 mm each, were inserted under direct vision, the right and left lateral ports at the level of the umbilicus. Normally, right and left ports are inserted but it was impossible to reach the left side from the right port, therefore a further left port was inserted between the left lateral port and the Palmer's point port. The two left port placements facilitated exposure of the ovarian cyst, adhesiolysis of the bowel from the left adnexa, avoided potential injury to the gravid uterus and minimized uterine manipulation.She was admitted at 20 weeks' gestation. She was asymptomatic and the height of the fundus at 20 weeks corresponded to 26 weeks' gestation. After induction of general endotracheal anaesthesia, a nasogastric tube was passed to remove any gaseous distension of the stomach. The uterine fundus was palpated and a Verres needle was inserted through the Palmer's point. After insufflation with COAt laparoscopy, the gravid uterus was seen with normal right ovary with no ascites, smooth peritoneal surface, normal upper abdomen and no cyst could be seen. The left adnexa was obscured by congenital adhesions of the sigmoid colon and omentum. These are normally congenital adhesions from the sigmoid colon to the sidewall around the pelvic brim. Transvaginal ultrasound was therefore performed at this stage. The ultrasound scan confirmed an 11 cm simple cyst with thin septum in the pouch of Douglas behind the uterus. The bowel adhesions to the left adnexa were divided. The cyst was still not visible so the operating table was tilted towards the right which deflected the uterine fundus away from the midline. At this point, a small part of the left ovarian cyst was visualized between the pelvic side wall and the gravid uterus. The cyst was aspirated with a Verres needle avoiding intraperitoneal spill and 300 ml of serous fluid was drained initially. Once the cyst had shrunk, the ovary was pulled out from the pouch of Douglas. The remaining cyst was then completely aspirated (nearly 500 ml of more fluid). The pouch of Douglas was visualized, and looked normal. The ovarian cystectomy was performed by dissecting away the cyst wall from the ovarian tissue by stripping and sharp scissors dissection. The remaining ovarian tissue was refashioned with 3/0 PDS by purse string suture burying the ovarian edges. The pouch of Douglas and peritoneal cavity were washed with Ringer's lactate. The intra-abdominal pressure was maintained below 12 mmHg throughout the procedure. Theatre occupancy time for the whole procedure was 120 minutes. No tocolytics were used as there is no evidence for any role of tocolytics at this gestational age. Prophylactic antibiotics were administered. The fetal heart was auscultated before and after the procedure.Her postoperative recovery was uncomplicated and she was discharged home the following day. She was readmitted 12 days later due to anxiety and constipation resulting in some spasmodic abdominal cramps. She settled with reassurance, simple analgesia and laxatives. The patient was reviewed in the clinic 2 weeks later and discharged to routine antenatal care. Her subsequent antenatal course was uncomplicated. Histology of the cyst wall confirmed a mucinous cyst adenoma. She was admitted at 39 weeks in spontaneous labour and due to non-progress of labour, she had an emergency lower segment caesarean section. At operation, both her ovaries were normal and mobile. The baby was male and weighed 3.7 kg, with Apgar score 7 at 1 minute and 9 at 5 minutes.et al.[Laparoscopic cystectomy in pregnancy was first reported in 1991 by Nezhat et al.. Since tThe frequency of ovarian tumours is about 1 in 1000 pregnancies  and thosManagement of the adnexal mass, whether it be conservative or surgery, remains controversial. Surgical removal is considered to reduce the risk of undiagnosed malignancy, torsion, infection, rupture, haemorrhage and obstruction of labour. These complications may necessitate emergency surgery which carries a higher risk of fetal wastage compared with elective surgery. Furthermore, the risk of obstruction of labour is calculated to be 17% to 21% . OperatiOnce the decision is made for surgical management, the specific approach is the next consideration. Until recently, most of these procedures were performed by exploratory laparotomy. There is evidence to suggest that laparoscopy and laparotomy do not differ with regard to fetal outcome, that is, fetal weight, gestational age, growth restriction, infant survival and fetal malformations . HoweverThe possible risks of laparoscopy include compression of uterine blood flow through elevated intra-abdominal pressure, fetal acidosis, fetal exposure to carbon monoxide from coagulation and uterine injury from cannula placement. The risks of hypercarbia and acidosis are reduced by keeping the operating time short and pressures as low as possible - no higher than 15 mmHg. Ventilation of the lungs needs to be carefully monitored and constantly adjusted to compensate for the pneumoperitoneum and positional changes. For operative laparoscopy, adequate exposure is possible with low pressure, although a short period of higher pressure increases the safety of port insertion ,10.Although laparoscopic surgery during pregnancy is becoming more common, it is rarely performed late in the second trimester. The enlarged uterus makes surgery more challenging. Laparoscopic cystectomy up to 27 weeks' gestation has been reported when the cyst contents were aspirated and the cystectomy was performed after exteriorization . MoreoveThe laparoscopic entry technique is less of a concern in the first trimester because the pregnant uterus remains in the pelvic cavity. However, with increasing gestational age, the uterus rises out of the pelvis and there is an increasing chance of injury while inserting the Verres needle. Generally, open cannulation laparoscopy or Palmer's point entry is recommended for laparoscopy during pregnancy. This avoids the risk of penetrating injury to the pregnant uterus by either the Verres needle or the trocar cannula .et al. described a series 48 laparoscopic procedures performed in 47 patients with adnexal masses in pregnancy and two cases required laparotomy due to dense adhesions and difficulty with haemostasis [In the case series and reports in the literature, there is usually no difficulty in exposing the adnexal mass as the enlarged pregnant uterus tends to displace it towards the top of the uterus. Mathevet mostasis . HoweverLarge cystic masses may require decompression to fit though a small incision. By decompressing a cyst into a laparoscopic bag, spillage can be minimal or non-existent. Copious irrigation also helps to keep the residual content to a minimum . After cThis case demonstrates that, at 20 weeks' gestation, an ovarian cystectomy is possible for an 11 cm cyst impacted in the pouch of Douglas using the laparoscopic approach and with a surgeon skilled in advanced laparoscopic techniques.Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.The case was managed and operated by AKT. The literature search and case writing were carried out by FS. The authors have read and approved the final manuscript.


Surveys in Vietnam have indicated that wasting and stunting have been prevalent among children, but the country is undergoing rapid socio-economic changes and little has been known about the relative situation in the different areas of the country. In 2006, the WHO introduced new growth standards applicable to all infant and child populations, which facilitates for improved assessments of the prevalence of growth impairment, independent of time, place and ethnicity. The aim of our study was to assess the growth of singleton infants delivered at term in three main birth clinics in the Khanh Hoa province in Vietnam by using the new WHO standards as reference, and the association between growth and some maternal, birth and health factors.A cohort of 237 singleton infants born in the period May-July 2005 in three main delivery clinics in the Khanh Hoa province were observed prospectively. Their anthropometrical measures a year later were compared to the WHO sex-specific growth standards for weight-for-age, length-for-age, weight-for-length, and BMI-for-age. These measures were analysed as dependent outcomes using multiple linear regression models including the following independent factors: urban vs. rural birth, 1-minute Apgar score, weight and length at birth, duration of lactation, ever had diarrhoea, dengue fever, pneumonia or dysentery, and maternal age, height, gestational duration and parity.th percentile for length-for-age, 9.6% for weight-for-age, 20.3% for weight-for-length, and 19.8% for BMI. A lower length- and weight-for-age were statistically associated with being born rurally.Compared to the standard distributions, 79% were below the median for weight-for-length; 18.0% were within the 5th percentiles for length-for-age, weight-for-length and BMI in late infancy were 3-4 times higher than expected, which indicate that deficient growth is prevalent. The infants born in a rural area had a lower weight- and length-for-age than their urban counterparts, independent of diarrhoea.In this delivery-clinic based sample of children in the Khanh Hoa province in Vietnam, the proportions within the WHO-standard 5 Human growth is sensitive to the environment, and a child may be inhibited from reaching its genetic growth potential if nutritional, socio-economic, health, or environmental factors are unfavourable prenatally or postnatally ,2. In gephysiological needs for growth and development are met during important childhood periods periods [, and areperiods [.th percentile of the standard, inferior growth is present [There are several measures of infant and child growth and size. Each measure has its weaknesses and strengths, and no measure is ideal during a long period of growth as the correlation between height and weight varies . Thus, t present .According to estimates by the WHO (2006) about 1/3 of children under age five in Vietnam are stunted and/or underweight for age . Anaemiath percentile for weight-for-length and weight, height (length) and BMI-for-age, respectively, different than 5 percent; and 2) were any of the following factors important determinants of the size of the children in late infancy: gestational duration, rural or urban district of birth, 1-minute Apgar score, weight and length at birth, duration of lactation, anaemia at follow-up, diarrhoea, pneumonia, dysentery or dengue fever in infancy (grouped as one factor), and maternal age, height and parity.The aim of this study was to assess whether the growth of singleton infants born at term in three main delivery hospitals in the Khanh Hoa province in Vietnam fell in line with the percentile distributions in the new WHO standards; the prevalence of impaired growth; and the association between different maternal and infant factors and the infants' growth. The specific study questions were: 1) was the proportion within the standard 5The study was carried out in the province capital Nha Trang located at the south-central coast (363 000 inhabitants) and the nearby inland rural district Dien Khanh (126 000). There were 32 delivery wards in Nha Trang and 26 in Dien Khanh. In 2005, the number of births was 5972 and 1925, respectively.In the three main delivery units , a total of 245 consecutive women in routine third-trimester pregnancy care were invited to participate in a follow-up study of their newborns; five (2%) chose to not participate. The enrolled women delivered 242 newborns in the period May-July 2005, whereof 237 were live born and singleton (128 in Nha Trang and in 109 in Dien Khanh). The following baseline data were collected about each birth in a standard form: the name of the clinic, maternal age, weight, height, parity, gestational age (determined by date of last menstruation), pregnancy and delivery complications and delivery date, and neonatal 1-minute Apgar score, sex, birth weight, length, head circumference and presence of congenital malformations. Additional details about the enrolment and baseline data collection have previously been published .After a year  the weight and length of each infant was measured and the mother asked about diseases and lactation while visiting the local health centre. A home visit was carried out to those who did not appear at the centre. The data were supplemented by clinical observations of diarrhoea and diseases in infancy. The weight of the child was measured to the nearest hectogram using Health Scale model TZ 120 and the length to the nearest centimetre in recumbent position. The latter was measured using the tool made and used by the National Programme of Nutrition for Children in Vietnam. The data collection was carried out by nurses and supervised by the Pasteur Institute in Nha Trang; initiated in co-operation with the University in Tromsø and Norsk Institutt for Luftforskning, Norway.The mean birth weight at baseline 51% boys) was 3201 grams  and length 48.4 cm (CI: ± 0.3 cm). Four (1.7%) of the infants weighed less than 2500 grams, but all had at least 37 weeks of gestation, and 3 were born with an anomaly. The mean maternal age was 27.8 (CI: ± 0.7) years (mode = 27). Some 44 percent of the enrolled women delivered for the first time. The main birth characteristics are presented in Table % boys wa2)-for-age as measures. The measures of each infant were compared with the WHO sex-specific growth standards for age in months and weight-for-length to determine where they fell in the standard percentile distribution [th percentile estimated. In addition, a linear multiple regression model was set up using each of the four measures as outcomes to analyse their association with the following a priori chosen factors: gestational duration, district of delivery, 1-minute Apgar score, weight and length at birth, duration of lactation, anaemia at follow-up, birth defects, diarrhoea, pneumonia, dysentery or dengue fever (grouped as one factor) before and after age 6 months, respectively, and maternal age, height and parity. The parameter estimates were adjusted for infant age at follow-up (in days) and sex. The significance level was set at 5 percent in each test and 95 percent confidence intervals (CI) presented. The goodness-of-fit of the models was visually evaluated by comparing normal probability plots and residual plots for each included variable.The infant size at the age of follow up was analysed using weight- and length-for-age, weight-for-length, and BMI  of the newborns were located at follow up. Their mean age was 369 days (range 320-413). The unadjusted length varied from 65 to 96 cm and weight from 5.8 to 14.0 kg. On average, the length had increased by 26.8 cm (range 15-53) and the weight by 5.9 kg (CI: 3.3-10.1). Boys had a higher weight, length, weight-for-length and BMI than girls. Twelve (5.4%) of the infants had been clinically observed with diarrhoea and one with dysentery, pneumonia and dengue fever, respectively. Of these, 5 were diagnosed before age 6 months. 29 women (15%) had terminated lactation before the follow-up. The mean duration and range of breastfeeding, outcome measures and proportion of data missing at follow-up are presented in Table th percentile for length-for-age, 9.6  percent for weight-for-age, 19.8  percent for BMI, and 20.3  percent for weight-for-length. Compared to the standard 25th percentile, 36.7 percent were below for weight, 39.2 percent for length, and 38.2 percent for weight-for-length. The median infant had a length-for-age similar to the standard but a lower weight-for-age and weight-for-length. The proportion above the 95th percentile was similar to the standard for weight-for age, but higher for length-for-age. The detailed distributions of growth for age compared to the standards for all four outcome-measures are presented in Table A higher proportion of the infants was in the low end for weight, and in both the low and high ends for length compared to the standard distributions. 18.0 95% CI: 13.0, 23.0) percent were within the standard 5.0, 23.0 Duration of breastfeeding and anaemia were not associated with the outcome in any of the four models and were removed to decrease the number of observations lost in the analyses due to missing values. The adjustment factors and remaining study factors explained 17 percent of the variance in length, 25 percent of weight, 14 percent of weight-for-length, and 6 percent of BMI. Infants born in Dien Khanh  were 2.2 cm shorter (CI: 0.5-4.0 cm) and weighed 550 grams less (142-957 grams) for age than those born in the city, adjusted for the other factors. The adjusted weight increased on average with 43 grams (6-80 grams) per cm increase in maternal height in the range 144-167 cm. No study factors were statistically associated with weight-for-length and BMI. Birth defects were not included in the multiple analyses as only two of the children available at follow-up were inflicted . The parameter estimates (beta) for the study factors for each of the four study outcomes are presented in Table The tolerance was at least 0.5 for every factor in each of the final models, which indicates that multi-colinearity was not present. Ten (4.5%) of the observations at follow up had missing values for one or more of the covariates. Running the models post hoc without the two most outlying observations of weight and length at follow up did not change the parameter estimates, but strengthened the association between district of birth and weight.A higher proportion of the cohort was in the low end of the standard distribution than expected for all four outcome-measures. On an individual basis, a low weight and/or length for age is either due to normal variation in growth or a deficit in growth. The employed WHO growth standards were based on the growth of healthy infants and children in several countries, including developing countries , and incNation-wide surveys of the prevalence of malnutrition in the age group 0-5 years found a substantial reduction in Vietnam between 1990 and 2004. Nevertheless, the prevalence of stunting was estimated to 31 percent and wasting 8 percent in 2004 . A surveth percentile of the growth standards for the study factors listed in Table th percentile of the standards than on the overall growth in the cohort, but stunting appears to be more common in the rural area independent of diarrhoea.To examine the infants in the low end of the standards closer, we carried out post-hoc analyses (by multiple logistic regression) of the risk of being within the 5More studies are needed to map the situation, and to evaluate whether the Vietnam government's anti-malnutrition programme has had an effect and their target for the under-five population been reached . Our finStudies in Vietnam have reported that the growth of Vietnamese infants began to lag behind a Western reference population from age four-five months ,21. The Nevertheless, the overall mean weight and length at follow-up were higher than that reported from a study in Hanoi a decade ago , and theWe found no association between length at birth and weight and length at follow-up, which is in accordance with findings that infants small at birth tend to catch up during the first year of life . The difexclusive breastfeeding, but it is known that exclusive breastfeeding beyond 6 months is negatively associated with infant growth in both weight and length [Sixteen newborns 6.8%) were lost to follow up because the mothers did not live at the address given to the birth clinic. It is common that pregnant women in Vietnam travel to their home district and their mothers, and deliver there. Our study sample met well the baseline inclusion criteria behind the WHO growth standard . Namely,d length ,8,23.% were loMeasurements of length and weight are often difficult to obtain in a primary care setting , but no As the study sample was recruited from the three main delivery clinics, it represented well infants delivered in the main clinics in the province, but was thereby less representative of children born in the numerous small delivery wards. In addition, the rural population was overrepresented in the sample compared with the proportion in the newborn population in the province as a whole. Thus, in terms of the magnitude of the estimates, the external validity of the study was limited. On the other hand, that a relatively large difference in birth weight was detected between rural and urban areas was likely not influenced. Furthermore, there was a relatively high proportion within the low tails of the standard distributions even though only children born in the main delivery clinics were included. The proportions in the provincial population as a whole might be even higher.th percentiles of the standards were 3-4 times higher than expected. Our findings indicate that deficient growth is prevalent in this province, and that infants born in a rural area had a lower weight and length in late infancy than their urban counterparts - independent of the occurrence of diarrhoea. Interventions to prevent deficient growth early in life are still needed in Vietnam - also in the Khanh Hoa province.The distributions of length-for-age, weight-for-length and BMI in late infancy of children born at term in central delivery clinics in the Khanh Hoa province in Vietnam deviate from the WHO standards. The proportions within the 5Our interpretation of the data or presentation of the findings has not been influenced by our personal or financial relationship with other people or organisations.AV analysed and interpreted the data, and wrote the manuscript. DVT lead the enrolment of participants, data collection and data entering. DTP organised the investigation and supervised the data collection. TS designed and supervised the study and data collection, and helped drafting the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/10/62/prepub


The objective of this cohort study was to examine the effect on birth weight of living in a disadvantaged neighbourhood in a Nordic welfare state. Birth weight is a health indicator known to be sensitive to political and welfare state conditions. No former studies on urban neighbourhood differences regarding mean birth weight have been carried out in a Nordic country.A register based on individual data on children's birth weight and maternal risk factors was used. A neighbourhood characteristic, i.e. an aggregated measure on income was also included. Connections between individual- and neighbourhood-level determinants and the outcome were analysed using multi-level regression technique. The study covered six hundred and ninety-six neighbourhoods in the three major cities of Sweden, Stockholm, Göteborg and Malmö, during 1992–2001. The majority of neighbourhoods had a population of 4 000–10 000 inhabitants. An average of 500 births per neighbourhood were analysed in this study.Differences in mean birth weight in Swedish urban neighbourhoods were minor. However, gestational length, parity and maternal smoking acted as modifiers of the neighbourhood effects. Most of the observed variation in mean birth weight was explained by individual risk factors.Welfare institutions and benefits in Sweden might buffer against negative infant outcomes due to adverse structural organisation of urban neighbourhoods. Birth weight is an important indicator of infant health. Several individual risk factors like age, gestational age, preterm births, multiple pregnancies and diseases such as pre-eclampsia influence birth weight . PreviouAccordingly, recent research has turned to contextual factors to provide a more complete explanation of the sources of social disparities in birth weigh ,11. LiviWe found no previous studies on urban neighbourhood differences regarding mean birth weight from a Nordic country. Yet, there is a pattern of segregation also in Swedish neighbourhoods which has been comprehensively described by geographers such as Andersson and Molina ,24. SwedPut together, the evidence of an impact of residential segregation on birth weight is based on research stemming from liberal Anglo-Saxon nations where the accent is on a minimal state and "as much market as possible" . FurtherIn this study we aim to investigate any neighbourhood effects on birth weight in the Swedish society. As demonstrated above, neighbourhoods in the major cities of Sweden exhibit rather great social differences. However, negative health effects of living in disadvantaged neighbourhoods might be modified by a system of equalising resources. The following three specific research questions were addressed in the study:1. What is the effect on birth weight of living in a disadvantaged neighbourhood, when individual-level factors, i.e. mothers' social position and other relevant confounders, are controlled for?2. How much of the variation in birth weight between areas can be attributed to the neighbourhood composition of individuals [i.e. intra-class correlation]?3. How much of the residual variation in birth weight between neighbourhoods can be explained by neighbourhood economic status after controlling for individual determinants?The study population consisted of 330 096 singleton live births to mothers who delivered between 1992 and 2001 in the three major cities in Sweden, Stockholm, Göteborg and Malmö. The cities were divided into 696 neighbourhoods. Neighbourhoods with < 500 inhabitants or in which no infants were born during a study year were excluded from the analyses  were derived from the Medical Birth Register . Absurd Areas in the region are defined as neighbourhoods based on natural geographic borders and homogeneity of housing . The agg'Economic status' was calculated as the ratio of low-to high-income earners in the neighbourhood (LH-ratio). Income earners are divided into three classes, low, normal and high. Low income earner is defined as belonging to the lowest quintile of income earners in the actual region; Stockholm, Malmö, Göteborg. In 1990 persons with an income below 123,300 SEK, 114,500 SEK and 123,800 SEK respectively were defined as low income earners. In 2002 corresponding limits were 151,600 SEK, 121,600 SEK, 150,200 SEK. High income earner is defined as belonging to the highest quintile of income earners in the region. In 1990 persons with an income above 255,400 SEK, 225,300 SEK and 232,500 SEK respectively were defined as high income earners. In 2002 corresponding limits were 406,800 SEK, 352,400 SEK, 364,600 SEK. Thus, in affluent neighbourhoods, where high income earners are more numerous than low income earners, this ratio is far less than 1. Correspondingly, in poor areas with more low income earners the ratio by far exceeds 1.The rationale for using this ratio is that not only the prevalence of low income earners in an area but also of high income earners plays an important role for the neighbourhood social climate. Having a high income coincides for example with better education and high income household can be assumed to have a strong demand on public and commercial services of good quality, such as schools, primary care etc in their neighbourhood. Accordingly, the presence of high income households constitutes a stabilizing factor within the neighbourhood and as such is beneficial to the whole area.Table The multilevel analyses were conducted using hierarchical modelling technique ,42. We ee2 is the variance at the individual level.where Thereafter we elaborated the random intercept and random slope models, consisting of two equations estimated simultaneously, an individual-level model and a neighbourhood-level model . The varYij is the infant's birth weight for mother i in neighbourhood j; βj 0is the overall constant (intercept); βj 1is the random slope for year of birth in neighbourhood j, β1Xij 1+...+ βp Xpij are the partial effects of individual-level variables on birth weight; and eij is the individual-level variation in birth weight.where βj0, is allowed to vary randomly across neighbourhoods, as follows:In the neighbourhood-level model, model 3, the intercept from the individual-level, γ00 is the average-value birth weight across all neighbourhoods, γ1j is the average slope across the years of birth included in the model, and γ0q is the neighbourhood-level effect; Zqj is a neighbourhood-level determinant; and u0j is the variation at the neighbourhood level. The neighbourhood-level model estimated neighbourhood effects before adjusting for individual-level covariates.where Models 4–6 added individual maternal risk factors. Biological factors, socio-demographic variables and maternal smoking were entered in three steps. Non-significant variables were excluded from further analyses.Finally, relevant cross-level interactions between significant neighbourhood and individual-level variables were explored. No interaction variables reached significance and were therefore not entered in the model.Variance components for the individual- and neighbourhood-level models are presented. The between-neighbourhood variation was described as the proportional change in variance in the individual-level model and the neighbourhood-level model compared with the null model . ParametTable The results of the multi-level analysis for continuous birth weight are presented in Table In model 2 the time variable was entered as a random coefficient, allowed to vary by neighbourhood. The time trend signified an increase in ICC from 0.62 % the first year of observation to 1.7 1% the last year of observation.In model 3, unadjusted neighbourhood-level coefficients are estimated. The reason for showing unadjusted neighbourhood estimates is that many of the individual-level controls may actually reflect the effects of prior neighbourhood conditions. Compared to the null model the between-neighbourhood variation was reduced by 66.9%. There is a linear trend in the fixed effects of neighbourhood economic status. In the poorest neighbourhoods infants on average weighed 171 g less than did infants from the most affluent neighbourhoods. The estimates are significant.When biological factors, maternal height, length of gestation, and parity, were entered into model 4, the effect of neighbourhood economic status was only significant in the poorest neighbourhoods. The between-neighbourhood variation was reduced by an additional 19 %.Maternal age and maternal education were highly correlated and therefore only maternal education was entered in model 5. Women with low education gave birth to smaller children. The effect was significant but when maternal smoking was included in model 6, the effect of maternal education became insignificant. The variable was therefore excluded from further analyses.When individual-level covariates were introduced, the fixed effect of neighbourhood economic status remained significant only in the poorest neighbourhoods. In model 3 the birth weight was 172 g lower in poor neighbourhoods compared with the most affluent neighbourhoods. When significant individual-level variables were included, this effect decreased to 56 g.Our results suggest that the effect on mean birth weight of neighbourhood economic status is mediated by individual gestational length and parity. This is interesting since it is line with earlier findings where woman's exposure to stress partly explains preterm birth ,7.Further, smoking during pregnancy is a modifier of the neighbourhood effect on birth weight. To live in a disadvantaged neighbourhood can be interpreted as a stressful exposure to the pregnant woman but can also mirror a neighbourhood where unhealthy habits like smoking during pregnancy is more socially accepted . Indeed,This conclusion is supported by an intra-class correlation of less than 1%. Earlier multi-level studies in this field have not presented such components of variance, which is unfortunate. Estimates of explained between-neighbourhood variance direct focus on places instead of people and are therefore of importance to practitioners in the field of public health -51.The study design is cross-sectional. However, data on exposure to a neighbourhood context preceded the outcome under study. At the time of giving birth the women had all lived in their neighbourhood for at least 1 year and most of them for a longer period of time. The validity of these exposure data can therefore be considered good. Furthermore, the study relies on register data. The Medical Birth Register has been validated and found to have good validity . Also, rThis study is carried out in Sweden, which is described as a state with a pronounced responsibility for the welfare of the individuals, such as universal social benefits, gender equality seen in high female labour market participation, and a general and free maternal health care. We can not conclude that our negative results, i.e. the minor differences in mean birth weight in Swedish urban neighbourhoods depend on the welfare social policies in Sweden. However, Chung and Muntaner could show that more protective types of welfare regimes, namely the group of Social Democratic countries, were able to provide a more population health-friendly environment to its citizens in the last 39 years . Thus, iThe author(s) declare that they have no competing interests.ES outlined the design of the study, analysed the results, participated in the statistical analyses and drafted the manuscript. AH provided data and participated in the analyses of results. GA performed statistical analyses. SB participated in the design of the study and the drafting of manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The risk of retinoblastoma and rhabdomyosarcoma, but not other tumour types, was positively associated with increased growth, suggesting a possible role of fetal growth factors. Larger studies are needed.Using population-based linked health data, we investigated whether the risk of certain childhood non-CNS solid tumours ( Birth weight has been frequently studied in relation to risk, and is one of the few factors for which positive associations have been reported. However, birth weight studies of childhood non-central nervous system (non-CNS) solid tumors have produced inconsistent results and few have taken account of gestational age to differentiate between an association with birth weight per se from one with accelerated intrauterine growth. The mechanism(s) underlying the observed associations has not been well elucidated, but insulin-like growth factors (IGFs) have been implicated  (n=69), retinoblastoma (n=38), Wilms' tumour (n=52) and rhabdomyosarcoma (n=27).We analysed anonymised, population-based data from the Western Australian Data Linkage System , ‘proportion of optimal birth length’ (POBL) and ‘proportion of optimal weight for length’ (POWFL) .The sex distribution varied by type of tumour, with a higher proportion of males than females with neuroblastoma and retinoblastoma, more than half of which with were diagnosed before 2 years of age. The proportion of first-born children was higher in each tumour group than in the non-case group .The risk of retinoblastoma (HR: 0.54) was lower among girls than boys . Overallper se and one with accelerated growth. We restricted the univariate regression analysis of POBW to, in turn, children with birth weights below two commonly used definitions of high birth weight: >3500 and >4000 g. The positive associations observed between POBW and retinoblastoma and rhabdomyosarcoma were also observed among children with birth weights <3500 and <4000 g: retinoblastoma ; and rhabdomyosarcoma .As in our approach with childhood ALL , or disproportionate (increased soft tissue with a raised body mass index/POWFL). Insulin-like growth factors play a major role in regulating the normal growth and differentiation of cells and tissues during fetal development (This study has some important strengths. Examining risk associated with the appropriateness of IUG allows a more detailed exploration of this relationship than using birth weight alone or birth weight with adjustment for gestational age. We were able to explore associations between some specific solid cancers of childhood and three distinct aspects of IUG: POBW, POBL and POWFL. The z-scores for each of these were modeled appropriately as continuous variables and this method obviated the need to assign an arbitrary cutoff for ‘high birth weight’. Being a population-based, record-linkage study, neither selection bias nor recall bias would have affected our results.per se.There were small numbers of cases in this study and many results were only suggestive of an association; however, our findings are consistent with literature describing biologically plausible mechanisms for associations between increased fetal growth and risk of some non-CNS solid tumours. The persistence of our results when the analysis was restricted to children without high birth weight further supports an association with accelerated growth, rather than high birth weight We recommend for future studies, the use of measures of the appropriateness of IUG rather than birth weight alone, particularly in large collaborative studies that can examine these relationships with greater power.


Over the past decade, much has been learned regarding the role of various cytokines in the pathogenesis of inflammatory bowel disease. Several cytokine ‘knockout’ models in mice have been shown to develop colitis, while alterations in the production of various cytokines has been documented in human Crohn's disease and ulcerative colitis. In recent years, attempts have been made to treat these diseases through modulation of cytokine production or action. This review focuses on the cytokines that have been implicated in the pathogenesis of inflammatory bowel disease. The evidence for and against a role for particular cytokines in intestinal inflammation is reviewed, as is the experimental and clinical data suggesting that cytokines are rational targets for the development of new therapies.


Sir,The congenital dermoid inclusion cyst (CDIC), the most common type of dermoid cyst of the head and neck, is a sofHere we describe eight cases of CDIC of the anterior fontanel, emphasizing the importance of early diagnosis and treatment of these lesions.Eight patients referred to the Children's Hospital Medical Centre in Tehran from March 2000 to 2005 for the surgical resection of dermoid cysts around the anterior fontanel. In all cases , the lesPatients were operated in the supine position, under sedation and local anaesthesia. The lesion was completely removed through an ellipsoid incision bordering the mass, which was easily dissected from the galea and periosteum, without damage to the sagital sinus or the cyst capsule. Histological investigation showed cysts lined by a thick, stratified squamous epithelium containing skin appendages  in all cases. The postoperative period was uneventful with no recurrence during the follow-up period of 1.5–6 years (mean = 3.2 years) .Dermoid cyst is a pathologic term for a cyst lined by squamous epithelium containing skin appendages . It has been classified into three categories: 1) Teratoma type congenital dermoid cysts, 2) Acquired implantation dermoid cysts, (3) CDIC resulting from the inclusion of displaced dermoid cells along the embryonic fusion line.[ Acquired TeratomaCDIC of the anterior fontanel is described as a slow-growing, nontender, soft lump covered with intact skin. These are usually observed at birth and develop gradually through he accumulation of secretions and internal desquamation.In spite of the presentation of this cyst at birth, the age of children admitted for surgery in this study ranges from two months to five years. Postponing the operation in some cases can be related to the parents' ignorance or their knowledge of the benign nature of the lesion that permits delayed surgery. Although a female predominance has been reported, we couldThese cysts arise mostly around the anterior angle of the fontanel.5 InteresMost lesions found around the anterior fontanel in infancy are dermoid cysts. Other im124Computed tomography (CT) scans demonstrate the lesion as an extracranial, encapsulated, low-density mass without enhancement (known as a fluid-containing cyst) that is sometimes accompanied by lytic bone lesions.7 Magneti3et al. found no direct relationship between the depth of the bone defect and time of presentation,[Although Chaudhari entation, all the Dermoid cysts of the anterior fontanel are excised for cosmetic reasons, to prevent infection, to obtain histological diagnoses, and to rule out malignancy.7–9 The ben bloc resection of the cyst is performed. Until now, there has been just one case of progression and slow recurrence six years after surgery.[As seen in our study, there is almost no recurrence if  surgery.