A hydatid cyst of the breast is rare and often goes unnoticed by mammography and ultrasound. Preoperative diagnosis may be performed using fine-needle aspiration cytology, which also minimizes the risk of intraoperative rupture.We report the case of a 70-year-old Spanish woman who was diagnosed with a hydatid cyst using fine-needle aspiration cytology before surgery.Fine-needle aspiration cytology is an accurate and safe technique that can allow surgery to be avoided, especially in older patients or patients with high surgical risk. Echinococcus granulosus. The definitive hosts of the parasite are dogs, whereas the intermediate hosts are sheep and other ruminants. Humans are accidental intermediate hosts of this organism. It is an endemic disease that particularly affects people who live in rural areas in intimate contact with cattle. As in other countries of the Mediterranean basin, it is endemic in Spain, where it remains a serious health concern in many of the affected regions . Durid cysts . Our casSpecific immunological patterns are rarely used to diagnose hydatid cysts of the breast. Serologic tests, such as enzyme-linked immunosorbent assay, indirect hemagglutination and immunoblot techniques, can be used to confirm the hydatid origin of a cyst diagnosed by imaging techniques. Recently, the quantitative assessment of serum-specific immunoglobulin E by the ImmunoCAP® system has been performed for the diagnosis of hydatid cysts . ElevateEchinococcus hemagglutination titers returned to normal [The complete excision of the hydatid cyst without any spillage is the choice and definitive treatment of hydatid cyst disease, irrespective of its location. The aims of surgical treatment are the total removal of all parasitic elements, the avoidance of cyst content release and the maximum conservation of the affected viscera. Accidental implantation may be prevented by irrigation of the cyst bed with a 3% saline solution. One study has reported patients who underwent surgical cyst removal followed by medical treatment until the o normal .Preoperative chemotherapy using albendazole has been shown to decrease the incidence of recurrent disease. However, it may not prevent disease recurrence in a distant site. Recurrence is typically due to either incomplete cyst removal or previously unidentified cysts. The reported recurrence rates range from 2% to 25% .In our case, FNAC was harmless and was without complications or allergic reactions. After explaining the benign nature of the nodule, cyst excision was refused by our patient. The calcification and morphological stability of the nodule over time suggests an inactivate lesion.Hydatid disease of the breast is a very rare localization of this disease, but it should be considered as a differential diagnosis of breast lumps for individuals residing in endemic areas and among migrant populations.The diagnosis is typically made postoperatively. Preoperative diagnosis is rare because the clinical and imaging findings are non-specific. FNAC can provide a safe, fast, inexpensive preoperative diagnosis and allow the planning of a cystectomy, minimizing the risk of intraoperative rupture.Written informed consent was obtained from the patient for publication of this case report and accompanying images. 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.MJC and MM analyzed and interpreted the patient data regarding the breast disease and the FNAC procedure. MJC and NM were major contributors in writing the manuscript. All authors read and approved the final manuscript.


EHP, researchers report preliminary evidence of an association between two birth defects and a mother’s residential proximity to natural gas wells at the time of birth.More than 15 million Americans are now estimated to live within one mile of a natural gas well drilled since 2000.“Studies like this underscore the need for more representative and comprehensive research on workers and communities to understand their exposures and potential health risks,” says Aubrey Miller, a senior medical advisor at the National Institute of Environmental Health Sciences.Researchers led by Lisa McKenzie at the Colorado School of Public Health estimated exposure to natural gas development for nearly 125,000 Colorado women. They used an “inverse distance weighting” method in which they determined the density of natural gas wells within a 10-mile radius of each mother’s home at the time she gave birth, with greater weighting for wells nearer the home. Then they compared proximity to gas wells between mothers who had adverse birth outcomes—including three types of birth defects, preterm birth, and term low birth weight—and those who did not.Among 59 cases of neural tube defects, prevalence was twice as high among babies of mothers in the highest exposure group—a group of 19 women with more than 125 wells per mile within a 10-mile radius of the home—compared with babies of unexposed mothers. However, there was no evidence that neural tube defects were increased among the 13 babies of mothers classified as having low or medium exposure.Among 1,823 cases of congenital heart defects, prevalence was 30% higher among babies of mothers in the highest exposure group, compared with babies born to unexposed mothers. In contrast to neural tube defects, however, the likelihood of a congenital heart defect increased steadily with increasing exposure. Congenital heart defects are the most common type of birth defect, affecting about 8 of every 1,000 newborns in the United States.There was no association observed between proximity to natural gas development and having babies with an oral cleft. In addition, babies whose mothers experienced the highest exposures to natural gas wells were slightly less likely to be born prematurely or at a low birth weight. However, the association between proximity to gas wells and improving birth weights diminished when the researchers accounted for elevation. “Higher elevations are associated with lower birth weights, while most natural gas drilling in Colorado occurs at low elevations,” McKenzie explains.,Although low levels of maternal folic acid—a B vitamin found in green leafy vegetables—is an established risk factor for neural tube defects,“The study certainly raises legitimate concerns, given that there are plausible mechanisms for many of the chemicals that are used in natural gas development,” says Kenneth Spaeth, medical director of the Occupational and Environmental Medicine Center at North Shore University Hospital inNew York, who was not involved in the study.The authors suggest that exposure to benzene from the wells is one such plausible explanation for their findings. However, they did not identify or measure specific pollutants that may have been present at natural gas wells or specific activities occurring at the sites, so it is not possible to know which chemicals and/or other environmental stressors—if any—explain the associations. It’s also possible that some other risk factor not associated with wells, such as mothers’ folic acid consumption or level of prenatal care, could have influenced the results.“Our findings are far from representing a causal effect,” says McKenzie. Her plans for future research include interviews with study mothers to get more information about their pregnancy and place of residence during the first trimester, a critical period for birth defect formation. She also plans to obtain more detailed information on specific activities taking place at well sites during the first trimester.


Background: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight.Objective: Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns.n = 191 pregnant women) and 11 phthalate metabolites (n = 287). Weight, length, and head circumference at birth were collected from maternity records. Statistical analyses were corrected for the oversampling of malformation cases.Methods: We conducted a case–control study on male malformations of the genitalia nested in two French mother–child cohorts with recruitment between 2002 and 2006. We measured, in maternal urinary samples collected between 6 and 30 gestational weeks, the concentrations (micrograms per liter) of 9 phenol : –129, –25] and by 49 g  in association with a 1-unit increase in ln-transformed 2,4-dichlorophenol (DCP) and 2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) ln-transformed concentrations were positively associated with weight  and head circumference at birth . Head circumference increased by 0.3 cm  in association with a 1-unit increase in ln-transformed BPA concentration. For phthalate metabolites there was no evidence of monotonic associations with birth weight.Conclusions: Consistent with findings of a previous study, we observed evidence of an inverse association of 2,5-DCP and a positive association of BP3 with male birth weight. Diesters of phthalic acid  and phenols are found in many consumer products. Low molecular weight (MW) phthalates (MW < 250 g/mol) are used in personal care products  or as coating for pharmaceutical products. High MW phthalates (MW > 250 g/mol) tend to be used in polyvinylchloride floor and wall covering, food packaging, and medical devices . PhenolsWidespread exposure to phthalates and phenols has been documented for pregnant women in several industrialized countries , 2009. SLittle is known about the consequences of prenatal exposures to phthalates and phenols on fetal growth. An American cohort study of 404 mother–infant pairs reported an inverse association for 2,5-DCP maternal urinary concentrations and a positive association for BP3 urinary concentrations with birth weight in male but not in female newborns .Our aim was to study the relationships between prenatal exposures to phthalates and phenols and weight, length, and head circumference at birth among male newborns.Study population. We conducted a case–control study of male malformations of the genitalia nested in the EDEN  and PELAGIE mother–child cohorts. These cohorts are described elsewhere (n = 48 in EDEN and 24 in PELAGIE). In addition, three male newborns without congenital malformation of the genitalia (controls) were matched to each case by recruitment center, date of recruitment (± 6 months), day of week (weekend yes/no), and gestational week when the maternal urine sample was collected, for a total of 288 mother–newborn pairs (72 cases and 216 controls). Participants provided informed consent for data and biological sample collection for themselves and their offspring. These cohorts received the approvals of the appropriate ethical committees. The involvement of the Centers for Disease Control and Prevention (CDC) laboratory was limited and determined not to constitute engagement in human subjects research.lsewhere . BrieflyOutcomes. We extracted from hospital maternity records weight, length, and head circumference assessed at birth.Exposure assessment. Urine was collected between 6 and 19 gestational weeks in the PELAGIE cohort and between 24 and 30 gestational weeks in the EDEN cohort. Assessment of biomarker and creatinine concentrations in maternal urine was done by the National Center for Environmental Health laboratory at the CDC in Atlanta, Georgia, USA . Nine phenols were measured in urine samples collected from mothers in the EDEN cohort only  (phenols could not be measured in the PELAGIE cohort because a preservative added to the samples interferes with the assay used).gia, USA . We measMolar concentrations of four metabolites of di(2-ethylhexyl) phthalate (DEHP)  were summed as total DEHP. Concentrations of phthalate metabolites of MW > 250 g/mol and of MW < 250 g/mol were summed as total of high MW phthalates (ΣHMW) and of low MW phthalates (ΣLMW), respectively. Total paraben concentration (ΣPB) was calculated by summing methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), and butyl paraben (BP) molar concentrations. Monoethyl phthalate (MEP) and monobenzyl phthalate (MBzP) concentrations have been corrected [multiplied by 0.66 (MEP) and 0.72 (MBzP)] because the analytical standards used were of inadequate purity .Statistical analyses. We replaced concentrations below the limit of detection (LOD) by LOD/√–2. We corrected the overrepresentation of congenital abnormalities, induced by the case–control design, using a reweighting approach. We used center-specific weights corresponding to the inverse of the inclusion probability of controls, so as to give cases and controls the same relative weight as in the original cohorts , gestational age at collection, duration of storage at room temperature before freezing, and season and day of sampling] using separate linear regression models for each biomarker adjusted for maternal age, body mass index (BMI) before pregnancy, parity, year of sampling, education, current occupation, active smoking, and center. Next, we used these data to estimate biomarker concentrations that would have been observed if all samples had been collected under the same conditions . Unless otherwise specified, all concentrations are the standardized values; we also report associations with biomarker concentrations not standardized for sampling conditions.p-values of trend tests were estimated using categorical variables whose values corresponded to the tertile-specific median biomarker levels. Situations in which biomarkers exhibited heterogeneity in outcome across tertiles  but with little support for a trend  were considered as suggestive of a nonmonotonic association.  We als segment . Adjustmt 60 kg) , maternat 60 kg)  or gestan = 17) or gestational diabetes (n = 15). All analyses were performed using STATA/SE, version 11 .We performed sensitivity analyses excluding women with pregnancy-induced hypertension  were considered as hypothesis-generating.To draw our conclusion, we gave more weight to results in agreement with our h weight . Other aStudy population. The 287 women were 29 years old, on average; 17% smoked during the first trimester of pregnancy : –86, –13] in association with a 1-unit increase in ln-transformed 2,5-DCP concentration. After categorizing exposures in tertiles, boys in the highest exposure tertile were 152 g lighter, on average, compared with boys in the lowest tertile  (http://dx.doi.org/10.1289/ehp.1103634)], consistent with the high correlation between 2,4-DCP and 2,5-DCP (r = 0.95). 2,5-DCP ln-transformed concentration was also inversely associated with head circumference at birth .299, –5) . We obseEach 1-unit increase in ln-transformed BP3 concentration was associated with an increase of 26 g in birth weight  and of 0.1 cm in head circumference at birth  .http://dx.doi.org/10.1289/ehp.1103634) for associations based on a restricted cubic spline model]. BPA concentrations were positively associated with head circumference, which increased by 0.8 cm in the highest BPA concentration tertile compared with the lowest tertile   in the second BPA concentration tertile and by 85 g  in the third concentration tertile, compared with the first .For all other phenols, there was no evidence of associations with offspring measures at birth .e > 0.14 . There wciations . For MECp-values for heterogeneity were observed with MCPP, monocarboxy-isooctyl phthalate (MCOP), monocarboxy-isononyl phthalate (MCNP), MEHP, and ΣHMW phthalates for birth length, and with ΣLMW phthalates for head circumference at birth ]. Using biomarker concentrations not standardized for sampling conditions instead of concentrations standardized for sampling conditions did not markedly change associations between birth weight and, variously, 2,4-DCP, 2,5-DCP, BP3, or BPA. Similarly, associations between head circumference at birth and either BP3 or BPA remained similar  in the whole study population, –79 g  after exclusion of cases, and –51 g  using nonstandardized biomarker concentrations [see Supplemental Material, Excluding women with pregnancy-induced hypertension or gestational diabetes did not modify our main results (data not shown).Within our study population of male newborns, maternal urinary concentrations of 2,4-DCP and 2,5-DCP were associated with a birth weight decrease, whereas urinary concentrations of BP3 were positively associated with weight and head circumference at birth. BPA urinary concentrations were positively associated with head circumference. There was no evidence of monotonic associations between phthalate metabolite concentrations and birth weight.Phenols and birth outcomes. In our study population, birth weight decreased by 152 g in the highest 2,5-DCP concentration tertile compared with the lowest tertile . The only other human study addressing this issue reported a decrease by 210 g in the third 2,5-DCP concentration tertile compared with the first   . Concent48, –71) . Dichlor48, –71) .2,4-DCP was also associated with a birth weight decrease. It is a metabolite of 1,3-dicholorobenzene, a minor contaminant of 1,4-dichlorobenzene , which mTaken together, these studies suggest an effect of dichlorophenols, or one of their precursors, on birth weight.BP3 urinary concentrations were positively associated with weight and head circumference at birth. Boys were 105 g heavier  in the highest BP3 concentration tertile compared with the lowest. Similarly, BPA urinary concentrations were positively associated with head circumference at birth. After categorizing exposures in tertiles, we observed an inverse U-shape association between BPA concentrations and birth weight. Such nonmonotonic dose–response curves between perinatal exposures to BPA and weight in early life have been reported in rodents . HoweverPhthalates and birth outcomes. There was no strong evidence of monotonic association between phthalate metabolite concentrations and birth outcomes, except for the possible positive association between MCNP and birth length. Our analyses suggested nonmonotonic associations with birth weight and birth length for some phthalate metabolites. To our knowledge, such associations between phthalate metabolites and birth weight have not been reported previously in rodents or in humans and therefore should be considered cautiously.Study population. To correct the overrepresentation of cases induced by our case–control design, we weighted the observations in regression models , but accurate information is not available on half-lives in pregnant women, in whom metabolism may differ compared with nonpregnant women. We assessed exposures from the urinary concentrations at a single point during pregnancy; increasing the number of urine samples collected would have provided a more accurate estimate of the average exposure during the whole gestation. We adjusted for many potential confounders, but residual confounding cannot be discarded. For example, specific metabolic disorders associated with both fetal growth and xenobiotic metabolism would constitute potential confounders. In our study, excluding women with pregnancy-induced hypertension or gestational diabetes did not alter associations with BPA and BP3 (not shown). Multiple comparisons are generally an issue in studies relying on several biomarkers. Although we did not formally correct for multiple comparisons, our choice to focus our conclusions on previously reported associations limits the risk of chance being a likely explanation for our main findings.In our study, there was no strong evidence of monotonic association between phthalate metabolite concentrations and birth outcomes. Urinary concentrations of 2,4-DCP and 2,5-DCP were negatively associated with birth weight, whereas BP3 concentrations were associated with a birth weight increase. Results concerning 2,5-DCP and BP3 are in agreement with another publication concerning male newborns from New York .(172 KB) PDFClick here for additional data file.


The aim of this study is to compare the odds of postpartum haemorrhage among women who opt for home birth against the odds of postpartum haemorrhage for those who plan a hospital birth. It is an observational study involving secondary analysis of maternity records, using binary logistic regression modelling. The data relate to pregnancies that received maternity care from one of fifteen hospitals in the former North West Thames Regional Health Authority Area in England, and which resulted in a live or stillbirth in the years 1988–2000 inclusive, excluding ‘high-risk’ pregnancies, unplanned home births, pre-term births, elective Caesareans and medical inductions.Even after adjustment for known confounders such as parity, the odds of postpartum haemorrhage (≥1000ml of blood lost) are significantly higher if a hospital birth is intended than if a home birth is intended . The ‘home birth’ group included women who were transferred to hospital during labour or shortly after birth.Women and their partners should be advised that the risk of PPH is higher among births planned to take place in hospital compared to births planned to take place at home, but that further research is needed to understand (a) whether the same pattern applies to the more life-threatening categories of PPH, and (b) why hospital birth is associated with increased odds of PPH. If it is due to the way in which labour is managed in hospital, changes should be made to practices which compromise the safety of labouring women. Studies of the comparative safety of home and hospital birth have tended to focus on perinatal death as the main outcome measure, rather than the question of whether planned home birth is safe from the perspective of the mother’s wellbeing. This is understandable; if planned home birth is associated with a greatly elevated risk of serious negative infant outcomes, then most women and clinicians would be reluctant to attach as much importance to other benefits it might offer. A few recent studies have concluded that under some circumstances there is a small increased risk to the baby if the mother plans a home birth ,2. HowevThe ultimate measure of the safety of birth from the mother’s point of view is maternal mortality. However, in developed countries maternal death is now so rare that it would be very difficult to construct a dataset that would allow a valid comparison of the relative risk of maternal death in different birth settings. Instead, we must consider other maternal outcomes that have the potential to lead to maternal death or to serious maternal morbidity. Postpartum haemorrhage (PPH) has been identified by the UK Care Quality Commission as one of three “potential markers relating to the risk of maternal mortality” .Previous research from the UK and Canada has identified a lower risk of PPH among planned home births than among planned hospital births ,11, but Using a unique UK dataset, this paper addresses the question: ‘is the incidence of PPH different if a home birth was intended than if a hospital birth was intended?’ This is the first time that a UK-based study has attempted to answer this question using multivariable analysis techniques to control for known confounders such as: parity, anaemia, maternal age and maternal BMI ,13. The This is an observational study involving secondary analysis of maternity records, in which information was recorded contemporaneously by health professionals as pregnancies progressed. In the UK, even if a home birth is planned, a pregnant woman receives maternity care from health care professionals who are based at an individual hospital, so the hospital records included planned home births as well as planned hospital births. The study data were taken from the St Mary’s Maternity Information System (SMMIS), a computerised records system which was used by most of the hospitals within the former North West Thames Regional Health Authority (RHA) area during the study period. Between 1988 and 2000 (inclusive), 15 National Health Service (NHS) hospitals contributed data relating to all the pregnancies for which they provided any maternity care. The participating hospitals came from a wide range of types and locations, so there is no reason to suppose that the results are unrepresentative of the region as a whole.A total of 585,291 pregnancies from the 15 hospitals were included in the SMMIS database. Studies have concluded that the completeness and quality of the information recorded within SMMIS is good. For example, studies comparing the information recorded on the database against case notes found a very high degree of corroboration , and a high level of consistency across different hospitals ,15.Figure Unplanned home births were excluded from the analysis because they would have all been classed as having intended a hospital birth and their inclusion would have artificially increased the risks associated with planning a hospital birth. It could be argued that unplanned home births are similar to planned home births which were transferred to hospital during labour (because birth did not take place in the intended location), and that not getting to hospital in time is a risk of planning a hospital birth, and for this reason we have run the analysis both with and without unplanned home births (see ‘results’ section). However, there is a fundamental difference between the two situations: transferring from home to hospital generally involves a considered decision made by the labouring woman and her partner in consultation with the attending midwife. Unplanned home births do not involve a considered decision – they are an unavoidable response to circumstances such as very quick labour. Planning a home birth would not have avoided this risk completely, because there is still a chance that that the midwife would not have arrived in time for the delivery. By contrast, planning a hospital birth would generally avoid the risk of having to travel to hospital during established labour.Research on the comparative safety of different birth settings tends to exclude ‘high-risk’ pregnancy; conventional wisdom states that women with ‘high-risk’ pregnancies should plan a hospital birth because they are at higher risk of negative pregnancy outcomes. In fact, there is little hard evidence to suggest that, if the pregnancy is ‘high-risk’, a negative outcome is more likely if a home birth is attempted, so there is an argument for including ‘high-risk’ pregnancies in this type of analysis, and this was attempted as part of this research project. The inclusion of ‘high-risk’ pregnancies in the analysis necessitated a significantly more complex model to control for the fact that the ‘intended hospital birth’ group contained a higher proportion of ‘high-risk’ pregnancies. Numerous conditions render a pregnancy ‘high-risk’, and the attempt to control for them all led to a model containing 27 covariates, which introduced the possibility of statistical problems such as collinearity. For this reason, the main results shown exclude ‘high-risk’ pregnancies. However, a model which included them was also fitted, with results given alongside the main findings for comparison.Women who were classed as not having had a birth attendant were also excluded. These were mostly women who had intended a home birth and had had very rapid labours . Presumably in these cases the baby was delivered before the midwife arrived at the woman’s home. It was therefore possible to categorise them with unplanned home births in terms of the circumstances surrounding their labours and births. As with unplanned home births, an argument could be made for including unattended births in the analysis, as giving birth unattended is a risk of planning a home birth, so, as a further sensitivity analysis, the model was re-run with these observations included (see ‘results’ section).Elective Caesarean sections were also excluded from the analysis. PPH was more common if the baby was delivered by Caesarean section than if born vaginally . Because elective Caesareans occurred only in the ‘intended a hospital birth’ group, their inclusion in this analysis would have artificially inflated the risk of PPH for hospital births, because elective Caesareans tend to be performed in response to fears about the safety of vaginal delivery, eg if the foetus is malpresented. For similar reasons, medical inductions (ie those using oxytocin and/or prostaglandins) were excluded. These too only occurred in the ‘intended a hospital birth’ group, so that comparisons would have become irrelevant if the cases had been included.There are a number of definitions of PPH. According to the Royal College of Obstetricians and Gynaecologists (RCOG), although an estimated blood loss of at least 500ml counts as a PPH, in the UK a case should be considered an “emergency” only when the blood loss exceeds 1000ml . For thiWomen were classed as having intended a home birth if: (a) a home birth was intended at booking and the baby was delivered at home, (b) a hospital birth was intended at booking but the baby was delivered at home, and SMMIS recorded the change in intention as having taken place before labour commenced, or (c) a home birth was intended at booking but the baby was delivered in hospital, and SMMIS recorded the change in intention as having taken place during labour. Thus, intrapartum transfers from home to hospital were included in the ‘intended a home birth’ group. Women were classed as having intended a hospital birth if: (a) a hospital birth was intended at booking and the baby was delivered in hospital, or (b) a home birth was intended at booking but the baby was delivered in hospital, and SMMIS recorded the change in intention as having taken place before labour commenced. Maternities were classed as unplanned home births if a hospital birth was intended at booking but the baby was delivered at home, and SMMIS recorded the change in intention as having taken place during labour.The risk status of a pregnancy was defined using a mixture of maternal International Classification of Disease (ICD) codes  and indiThe analysis was carried out using a logistic binary regression model, with PPH as the outcome variable and built using manual forward selection (with p < 0.05 as the cut-off). Because SMMIS contained over 200 items of information for each pregnancy, the list of potential covariates was a long one. Covariates were selected after a literature review of characteristics associated with intended place of birth ,11,21-23Some potential covariates were excluded from the modelling despite being associated with PPH: mode of delivery, type of health professional attending delivery, type of pain relief used in labour and augmentation of labour. This is because these factors may act as mediators and may explain the difference between home and hospital birth, and therefore holding them constant would have led to controlling for the effect of planned place of birth on PPH. Had the aim of this analysis been to identify characteristics associated with PPH, clearly these covariates would have been included , so it would not be appropriate to use these results to draw conclusions about the association between PPH and covariates other than intended place of birth.A number of covariates were not included in the final model because, after adjustment for the other model covariates, there was no significant association between them and PPH. These covariates are listed in Table Once the final additive model was built, interaction terms were tested, involving intended place of birth and: pregnancy risk factors, year, parity, maternal age and time of birth. None made a statistically significant improvement to the model fit.There were no missing data for the outcome variable. The approach for handling missing data for the explanatory variables depended on the extent of the problem. If fewer than 0.1% of records had data missing on a variable, these records were deleted. If between 0.1% and 12% of records had data missing on a variable, a ‘missing’ category was created and included as a separate measure within the model. If more than 12% of records had missing data on a variable, that variable was not included as a covariate.The Riverside Research Ethics Committee (REC) approved the project (REC reference number 08/H0706/42) on 17 April 2008.Among the 273,872 pregnancies which were used for the analysis described in this paper, there were 2,808 cases of PPH (1.02% of the eligible records). In the unadjusted data, the incidence of PPH was significantly higher in the ‘intended a hospital birth’ group than in the ‘intended a home birth’ group . We can therefore be confident that the results are not sensitive to the inclusion or exclusion of unplanned home births or unattended births.Also as noted in the ‘methods’ section, ‘high-risk’ pregnancies were excluded from the main analyses. We did, however, repeat the analysis including ‘high-risk’ pregnancies, and found that the odds ratio for intended place of birth was very similar . Great care was taken to control for pregnancy risk status because the ‘intended a hospital birth’ group contained proportionally more ‘high-risk’ pregnancies than the ‘intended a home birth’ group, and because ‘high-risk’ pregnancies were more likely to have PPHs. Pregnancy risk status was included in the model by treating each high- or medium-risk condition as a separate covariate. Thus, the model controlled for the facts that: (a) the ‘intended a home birth’ group contained a higher proportion of low-risk pregnancies than did the ‘intended a hospital birth’ group, and (b) among those with high-risk pregnancies, those who intended a home birth tended to have different high-risk conditions from those who intended a hospital birth.PPH is a relatively rare complication; it occurred in just 1% of the deliveries included in this analysis, so even with an odds ratio of 2.5, the absolute risk of an individual woman experiencing this complication is small. Nevertheless, it is a serious complication which is one of the leading causes of maternal death in the UK  and worlThe incidence of PPH for planned hospital births would be expected to be higher than the incidence for planned home births, because nulliparous women are more likely to experience PPH , rather than relying on the woman’s stated intention in the early stages of pregnancy. Thus, only those who intended a home birth at the Few, if any, existing studies of home birth in the UK can claim to have overcome this many of the problems commonly associated with the study of home birth. Therefore, this study makes a novel and valuable contribution to what was previously known about the safety of home birth.There were, however, limitations to the SMMIS database. It was collated over the period 1988–2000, the end date occurring more than 10 years ago. However, in the absence of a more recent dataset with the qualities possessed by this one, it represents the most up-to-date, high-quality information available from the UK. The data are also specific to one region of England, so care should be exercised when generalising these results to the UK as a whole. However, the North-West Thames region was large and diverse in terms of geography and demography, so there is no reason to suppose that the results are completely atypical of the rest of the country, with the possible exception of remote rural areas.It is notoriously difficult to estimate accurately the amount of blood lost during labour and delivery, and the normal method used  has been found to be inaccurate . HoweverSome potentially useful covariates were not included in the database; most notably whether or not the woman had had a PPH in one or more previous pregnancies. Previous PPH has been found to be a predictor of PPH , and it Because the SMMIS database covered a 13-year period, some women were included in the database more than once, due to having more than one pregnancy during those 13 years. For reasons of confidentiality, these repeated events are not identified on the SMMIS database. There will therefore be clustering effects that were not controlled for in the analysis. This will have affected the study’s conclusions if some women had an underlying propensity towards PPH that was carried through all their pregnancies, and if these women tended to plan for a hospital birth. To assess the extent to which this might be a problem, the model was re-run three times: once based just on women of parity 0 (first-time mothers), once on women of parity 1 and once on women of parity 2. Although the size of the odds ratio varied across these three parity groups, the overall pattern was the same, ie the risk was higher among those who intended a hospital birth. This indicates that the increased risk of PPH among those who intended a hospital birth cannot be explained by uncontrolled clustering effects.Pregnant women and their partners who are considering where to give birth should be informed that they may be at higher risk of PPH if they plan a hospital birth than if they plan a home birth. Future research should focus on possible explanations for the significantly higher risk of PPH among those planning a hospital birth, and address the possibility that procedures such as augmentation, emergency Caesarean section and episiotomy are over-used in the hospital setting.Future research should also attempt to establish whether or not these results also apply to more life-threatening categories of PPH , and whether the lower incidence of PPH among planned home births translates to fewer cases of PPH-related severe morbidity. Only when these questions are answered will it be possible to make a clear and confident statement about the relative safety of planned home birth in relation to PPH.BMI: Body mass index; CI: Confidence interval; ICD: International classification of diseases; NHS: National health service; NICE: National institute for health and clinical excellence; PPH: Postpartum haemorrhage; RCOG: Royal college of obstetricians and gynaecologists; RHA: Regional health authority; SMMIS: St Mary’s maternity information system database; UK: United Kingdom.The authors declare that they have no competing interests.Andrea Nove is a former PhD student from the Division of Social Statistics, University of Southampton, England. Ann Berrington is a Reader in Demography and Social Statistics at the Southampton Statistical Sciences Research Institute and ESRC Centre for Population Change, University of Southampton. Zoë Matthews is Professor of Global Health and Social Statistics at the Centre for Global Health, Population and Poverty, University of Southampton.AN was responsible for the study design and statistical analysis, with advice and guidance from AB and ZM. AN wrote the first draft of the paper; AB and ZM provided suggestions and all authors approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/12/130/prepub


IGF2-INS-TH region and in the G protein gene. Analysis of the genes in the IGF2-INS-TH region suggests that thrifty genotype has the effect of accelerating fetal growth, but at the same time a genomic imprinting mechanism is also involved. Analysis of the G protein β3 subunit gene unveiled that the 825T allele in the mother may exert influence on fetal metabolic environment. By extending the analysis to other genomic regions related to common adult diseases using the same technique, the detailed role of genetic polymorphisms may be elucidated.A close relationship between size at birth and occurrence of common adult diseases has been reported. As an explanation of this relationship, it has been hypothesized that the thrifty genotypes cause changes in growth efficiency during fetal period and diseases in later life. In the present study, we examined the association of fetal growth with genetic polymorphisms within the  It has been suggested that polymorphisms associated with susceptibility to common chronic adult diseases are present in the human genome. Genetic polymorphisms refer to the genetic differences among individuals at the level of DNA sequence. In principle, they do not contribute directly to disease, but they may affect the magnitude of gene expression. Neelin utero results in permanent reprogramming of fetal metabolism. In other words, genetic factors were not given a place in the ‘thrifty phenotype’ hypothesis.9Etiological studies have proved that birth weight is associated with not only postnatal prognosis but also common adult disorders including type 2 diabetes, dyslipidemia, hypertension, and atherosclerosis.in utero growth. With the recent advances in genetic technologies such as single nucleotide polymorphisms (SNPs) analysis, validation of common gene variants on a genome-wide scale has become feasible.Gene knockout animal models have shown the importance of genes encoding insulin (INS), insulin-like growth factors (IGFs) and their receptors, in regulating fetal growth and size at birth.IGF2-INS-TH region on human chromosome 11p15.5 has been associated with various common disorders including the metabolic syndrome, type 2 diabetes and coronary heart diseaseSome genes may affect not only fetal but also postnatal growth. Such candidate genes include those encoding INS, the IGFs, their receptors, and the respective post-receptor signaling cascades. The Numerous hormones, neurotransmitters, chemokines, local mediators, and sensory stimuli exhibit their characteristic effects on cells through binding with G protein-coupled receptors.IGF2-INS-TH region and in the G protein gene.In the present study, as a model case for genetic linkage between phenotypes during fetal stage and diseases in adulthood, we examined the association of fetal growth with genetic polymorphisms within the The subject population consisted of 884 mothers who delivered their neonates after 36 weeks’ gestation. The mothers were non-smoking Japanese women with no remarkable past history and an uneventful pregnant course. Each participant in the study gave informed consent according to a protocol approved by the local institutional review board.The parameters of fetal growth were birth weight, head circumference, and length. The actual measurements of birth weight, height and head circumference were converted into standard deviation scores (SDS) using the mean and standard deviation values of the standard somatoscopic curves at birth, by sex and by parity . For instance, birth weight SDS = /.Maternal and neonatal genomic DNA was prepared from the peripheral blood of mother and umbilical cord blood of neonate, respectively. Genotyping was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis.IGF2 gene, the +3123ApaI and +3580MspI loci were studied. The +3123ApaI polymorphism was genotyped for the presence  or absence  of the restriction site. GG genotype has been reported to be associated with adult obesity.ApaI genotypes with SDSs of birth weight are shown in ApaI genotypes; AA, AG and GG. GG homozygotes had a mean birth weight SDS of 0.18 higher than that of AA homozygotes (p = 0.01), and heterozygotes showed an intermediate mean value. No significant difference in birth weight SDSs was observed among the three maternal +3123ApaI genotypes. There was no significant difference in birth weight SDSs among the +3580MspI genotypes; AA, AG and GG, in both neonatal and maternal samples  or absence  of the restriction site. Among the neonates in the present study, the frequencies of the three genotypes for the −23HphI polymorphism were AA: 92.7%, AT: 7.3%, TT: 0%. The associations of neonatal and maternal −23HphI genotypes with SDSs of weight, head circumference, and length at birth are shown in HphI AT and AA genotypes in both neonates and mothers. No significant differences were also observed for head circumference and length SDSs at birth. Based on the segregation patterns of −23HphI alleles from mothers to neonates, neonatal −23HphIAT genotype could be subdivided into 2 types; paternal origin (A/pat T) and maternal origin (A/mat T) of T allele. The birth weight SDSs were significantly greater in −23HphI A/pat T neonates than in −23HphI AA neonates. Similarly, SDSs of head circumference and length at birth were significantly greater in −23HphI A/pat T neonates than in −23HphI AA neonates. In contrast, there were no significant differences in SDSs of the three parameters between −23HphI A/mat T and A/A genotypes.The −23The HUMTH01 is denoted by the number of tetranucleotide repeats; for example, allele 6 has 6 repeats of AATG. Five  of the HUMTH01 alleles described previouslyINS variable number of tandem repeats (VNTR) locus is located 596 bp 5’ to the INS initiation site, and is composed of tandem repetition of a 14–15 bp oligonucleotide consensus sequence.INS-VNTR has been classified into three distinct classes  according to the number of repeats of the oligonucleotide.HphI T allele and HUMTH01 allele10, which are linked to the INS–VNTR class III allele, were associated with increased weight, head circumstance, and length at birth. These associations confirm that variation within the INS region, most probably at the INS-VNTR, influences fetal growth. Furthermore, the finding that the paternally transmitted −23HphI T allele exclusively correlates with increased size at birth indicate the involvement of an imprinting mechanism.The in vitro studies, this truncated protein has been shown to be associated with enhanced activity of G proteins. Furthermore, G protein β3 subunit C825T polymorphism has attracted attention because of its association with common disorders in adults such as hypertensionG protein is composed of α, β, and γ subunits. Siffert et al.p = 0.028). The mean SDS values of neonatal head circumference were −0.227 and −0.150 for neonatal TT/CT and CC genotypes, respectively, and they were not significantly different.The association between maternal genotypes and neonatal somatoscopic characteristics at birth is shown in Therefore, we observed an association of the maternal  G protein β3 subunit 825T allele with reduced head circumference of the neonate. Although detailed mechanism of this association requires further research, our result suggests that expression of the β3 subunit 825T allele in the mother may exert an influence on fetal metabolic environment.IGF1 gene, and reported that alleles other than the wild type are related to lower birth weight and also associated with diabetes mellitus or cardiovascular disease in later life. However, the present study demonstrated that the association of the thrifty genotype is more complicated. Analysis of the genes in the IGF2-INS-TH region suggests that thrifty genotype has the effect of accelerating fetal growth, but at the same time a genomic imprinting mechanism is also involved.Using INS resistance as a model, Hattersley et al.IGF2 gene is involved in a number of potential pathways that may impact various metabolic and cardiovascular risk traits. A genome scan provided replicated evidence of linkage for abdominal subcutaneous and visceral fat on 11p15.5, especially in the IGF2 region.IGF2 gene depending on genotypes.ApaI GG genotype (reported to be related to adult obesity)IGF-II is a major fetal growth factor also expressed in adult life. The INS-VNTR class I/III genotype has been shown to be associated with type 1 and 2 diabetes,INS-VNTR class III correlates with increased size at birth. The INS-VNTR class III allele is related to regulated translation of the INS gene in the fetal pancreas, and it is speculated that lowered INS secretion causes INS resistance in fetal peripheral tissues. As far as nutrition supply is sufficient, peripheral INS resistance is thought to amplify anabolism of INS and stimulate growth, as is observed in the adolescent period.INS gene, or of neighboring genes regulated by the INS-VNTR.The IGF2 gene is a representative maternal imprinting gene. Analysis of INS-VNTR in type 2 diabetic parents-offspring trios has demonstrated that susceptibility to the disease was exclusively mediated by paternally derived class III allele.INS-VNTR allele for fetal growth, and their results remain controversial.INS-VNTR class III allele was associated with increased weight, head circumference, and height at birth. Thus our results indicate that INS-VNTR class III allele may also affect fetal growth in a parent-specific manner.Furthermore, the results of the present study is consistent with previous reports of the involvement of genomic imprinting in the association between class III allele and type 2 diabetes and also the fact that H19 gene also has been associated with birth size in smaller first-born infants.On the other hand, analysis of the G protein β3 subunit gene unveiled an entirely different pathway of involvement; that expression of the β3 subunit 825T allele in the mother may exert influence on fetal metabolic environment, perhaps through changes in the maternal intrauterine environment or maternal metabolism. While high glucose level in maternal blood caused by gestational diabetes can lead to fetal macrosomia, a more subtle change in blood glucose may also affect fetal weight gain, as demonstrated in a study of mothers with rare genetic defects of the glucokinase gene.Recently, the concept of “developmental origins of health and disease (DOHaD),”The study on the relationship between genetic polymorphisms and fetal growth has only started. In the future, by extending the analysis to other genomic regions related to common adult diseases using the same technique, the detailed role of genetic polymorphisms may be elucidated. Finally, as a future outlook, the utilization of genetic polymorphism data to customize nutrition management programs for individual mothers and fetuses may be realized.


Using the HFEA database of all 144,018 live births in all IVF cycles in the UK between 2003 and 2007, Scott Nelson and Debbie Lawlor show that couple- and treatment-specific factors can be used to help predict successful outcome following IVF. The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown.n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth , we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles . In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success  more than that of a previous spontaneous live birth ; p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia.We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 . In IVF, mature eggs are collected from the woman (or from an egg donor if the woman cannot make her own eggs) after a course of special hormones, and they are mixed in a dish with her partner's sperm. If her partner has a low sperm count or abnormal sperm, a single sperm can be injected directly into the egg in a procedure called intracytoplasmic sperm injection (ICSI), which became widely available in the mid 1990s, or sperm from a donor can be used. Finally, a number (depending on the country) of embryos (eggs that have begun to divide and develop) are put back into the woman where, hopefully, they will establish a successful pregnancy.Not every attempt at IVF is successful. In the US and the UK, IVF is successful in about a third of women under 35 years old but in only 5%–10% of women over the age of 40. It would be useful to have a way to predict the likelihood of a live birth after IVF for individual couples. Such a “prediction model” would facilitate patient counseling, clinical decision making, and the allocation of IVF resources. In this study, the researchers use information on IVF cycles collected by the Human Fertilisation and Embryology Authority (HFEA), which regulates IVF in the UK, to assess the extent to which the characteristics of infertile couples and the treatment they receive can be used to predict live birth after IVF. They also use these data to identify which factors are associated with preterm delivery, low birthweight, and macrosomia , three undesirable birth characteristics.Between 2003 and 2007, 163,425 IVF cycles were completed in the UK, 23.4% of which resulted in at least one live birth. The researchers used the data collected by the HFEA on 144,018 of these cycles (the other cycles had missing data) to develop a multivariable logistic regression prediction model  for the outcome of IVF. According to this model, a decreased chance of at least one live birth was associated with several factors including increasing maternal age, increasing duration of infertility, and the use of the woman's own oocytes. By contrast, a previous IVF live birth and the use of ICSI were associated with increased chances of success. Importantly, compared with an established multivariable prediction model, which was developed before the introduction of ICSI, the researchers' new prediction model predicted the chance of a live birth following IVF with greater accuracy. Finally, the researchers report that the chances of preterm and low birthweight after IVF were increased if donor eggs were required and ICSI was not used, that an increased risk of macrosomia was associated with increasing maternal age and with a history of previous live births, and that all three undesirable birth characteristics were associated with infertility due to cervical problems.These findings indicate that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have a low or high chance of a successful outcome following IVF. The prediction model developed here provides a more accurate assessment of likely outcomes after IVF than a previously established model. Furthermore, because the new model considers the effect of ICSI on outcomes, it should be more useful in contemporary populations than the established model, which does not consider ICSI. However, before this new prediction model is used to guide clinical decisions and to counsel patients, it needs to be validated using independent IVF data. To facilitate the external validation of their model, the researchers are currently generating a free web-based prediction tool and iPhone application (IVFpredict).http://dx.doi.org/10.1371/journal.pmed.1000386.Please access these websites via the online version of this summary at Human Fertilisation and Embryology Authority provides information on IVF and IVF statistics for the UKThe infertility and on IVFThe UK National Health Service Choices website provides information for patients on infertility and on IVFThe American Pregnancy Association has information for patients on infertility and IVF (in English and Spanish)MedlinePlus has links to further resources on history of the development of IVF is described on the Nobel Prize websiteThe http://www.IVFpredict.comThe prediction tool that was used in this study is at  In-vitro fertilisation (IVF) is now widely used for the treatment of infertility, and validated age-stratified national success rates and outcomes are published annually Given the known complications with multiple gestations and prematurity, the focus has moved to defining the most appropriate IVF outcome variable as a singleton term live birth In this prospective cohort study of 144,018 treatment cycles we assessed the extent to which baseline characteristics can be used to predict live birth after IVF-assisted conception, and for those cycles in which a singleton pregnancy was achieved we identified which factors were associated with preterm delivery, low birth weight, and macrosomia.The UK Human Fertilisation and Embryology Authority (HFEA), which is responsible for the regulation of assisted conception treatment in the UK, has had a Parliamentary statutory obligation to prospectively collect baseline information and birth outcomes on all licensed fertility treatment cycles performed in the UK since 1991 Maternal age, duration and cause of infertility, previous number of IVF attempts, number of previous spontaneous and IVF live births, source of gametes, and cycle number were recorded at the time of treatment. Duration of fertility, number of previous IVF attempts, number of previous pregnancies, number of previous IVF pregnancies, and total number of previous live births were all categorised in accordance with the previous analysis by Templeton For assessment of perinatal outcomes in cycles with a singleton live birth, gestational age at birth was defined as completed weeks of gestation. For the main outcome of preterm we examined multivariable associations with preterm birth, defined as ≤36 completed weeks; we also examined associations with extreme preterm (<33 wk). Birth-weight outcomes were supplied in 500 g increments and categorised as low birth weight (LBW <2.5 kg), normal (≥2.5 to <4.0 kg) or macrosomic (≥4 kg). In these analyses we included only cycles in which there was one heartbeat at 8 wk gestation and one live birth (i.e. these were singleton live births).We performed univariable and multivariable logistic regression to assess associations with at least one live birth. Given that the historical multivariable Templeton model p-value threshold of 0.05 to define statistical evidence of an interaction. The discrimination and calibration of this novel model was assessed as described above. The AUROC between the Templeton model and our model was compared using the ROCCOMP command in Stata The multivariable logistic regression model formed the basis of our novel prediction model of live birth. In the novel prediction model we used the same characteristics as those used in the Templeton model but included all causes of infertility , and allowed the coefficients for this and all other variables to be newly derived, and included four additional characteristics—the source of the egg (donor or patient's own), type of hormonal preparation used , whether or not ICSI was used, and the number of the treatment cycle . We tested all two-way interactions between pairs of predictors included in our multivariable analyses and used a Bonferroni-corrected (for multiple testing) Lastly, we examined model reclassification by determining the integrated discrimination improvement (IDI) of the novel prediction model compared to the original Templeton model To explore risk factors for adverse perinatal outcomes  we used logistic regression to examine the univariable and independent multivariable associations of all risk factors assessed in the multivariable analyses of at least one live birth, as described above. The selection of these potential risk factors for adverse perinatal outcomes was based on previous studies and the plausibility that risk factors that influence odds of live birth are also likely to affect gestational age and birth weight. For associations with preterm as the outcome we additionally adjusted for mean birth weight, and for outcomes with low birth weight and macrosomia we adjusted for mean gestational age. These analyses were conducted only for cycles in which there was only one heartbeat at 8 wk gestation and at least one live birth.All statistical analyses were performed using Stata version 11 (StataCorp LP).For the vast majority of variables there was no missing data; 3.9% of cycles had missing data on method of hormonal preparation used and 8.4% had missing data on duration of infertility; overall 12% of the eligible cohort had some missing data . UnivariN = 163,425) and the sample used for the main multivariable analyses . p<0.001 for linear trend) (r trend) .p-value for difference in estimate <0.001 .There was statistical evidence for four interactions, and stratified analyses reflecting these interactions are shown in p<0.001 comparing the novel model to the Templeton Of the 144,018 cycles 9931 (7%) were multiple pregnancies . Of these, 1,264 (13%) resulted in one live birth, 7,925 (80%) in two live births, and 109 (1%) in three live births; 633 (6%) did not result in a live birth. When we removed these 9,931 cycles from our analyses results were essentially unchanged from those presented here. For example, http://www.IVFpredict.com, and iPhone/Android application, IVFpredict) but also how both couple characteristics and treatment choice influence prognosis.n = 472). Characteristics that were associated with preterm birth in general were also associated with extreme preterm birth. In addition, extreme preterm birth was lower in 38- to 39-year-olds compared to all other ages and was increased in those who had a previous history of IVF.Of the 144,018 cycles included in our main analyses for prediction of successful live birth, there were 24,226 live singleton births; 24,096 (99.5%) of these had gestational age data and 24,050 (99.3%) had birth weight data. Mean (SD) gestational age was 38.98 (2.12) completed weeks, with 472 (2.0%) being less than 33 wk, 1,598 (6.6%) between 33–36 weeks and 22,026 (91.4%) 37 or greater weeks. Mean (SD) birth weight was 3.277 (0.629) kg, with 2,100 (8.7%) low birth weight (<2.5 kg), 19,704 (81.9%) a healthy birth weight, and 2,246 (9.3%) macrosomic (≥4.0 kg). In this study we identify precise estimates of the strength and independence of the factors affecting the odds of IVF success and their association with adverse perinatal outcome. To date, successful prediction of live birth after assisted conception has been limited, with a recent systematic review The use of assisted conception has increased dramatically over recent years, with concomitant increases in success rates, in part driven by the widespread uptake of ICSI for male factor infertility In keeping with all previous reports, live birth rates decline with increasing maternal age We examined the associates of preterm birth (<37 weeks the established definition of preterm). Although it is possible that obstetricians may consider IVF pregnancies as precious and have a lower threshold for iatrogenic preterm birth, we think this is unlikely because of the established associations of prematurity with neonatal respiratory complications We demonstrate that a previous live birth as a consequence of IVF has an even greater effect on the prospect of successful assisted conception therapy than does previous spontaneous conception. Although many couples undergoing assisted conception feel encouraged by achieving a pregnancy, even if it subsequently results in fetal loss, we found no beneficial or negative effect of a history of a nonviable pregnancy on live birth. This suggests that embryonic chromosomal errors, rather than a defective maternal environment, may be primarily responsible.Our work has a number of strengths. We have considered a range of anamnestic couple characteristics simultaneously with respect to validated live birth and perinatal outcomes rather than one or two in isolation. As a result, our data give a better overall reflection of predictive abilities, or lack thereof, for many factors. The size of our study was extremely large compared to other such studies in the literature. Finally, we considered a relevant multivariable historical model for consistency of findings before developing and assessing a novel prognostic model.We acknowledge, however, a number of limitations. Data were not complete on 12% of the eligible cohort; however, univariable analysis was similar in the whole cohort, and multivariable multiple imputation did not alter the overall conclusions (results available from authors on request). Treatment cycles rather than individual patients were identified because of concerns regarding confidentiality and breach of the terms of the HFEA Act, and therefore it was not possible to examine the effect of multiple cycles within one patient or to use robust standard errors that take account of clustering of women. However, the previous HFEA analysis could account for clustering and did not show a significant effect as compared with per treatment cycle For the main analyses with successful birth as the outcome we included both single and multiple pregnancy, i.e. our outcome was at least one live birth irrespective of whether there was one or more heart beats at 8 wk. Our reasons for doing this were, first, that this is a relevant outcome for infertile couples and, second, this was the outcome used in the study that developed the established prediction model, and therefore we wanted to test this model with the same outcome. Note that restriction of the data to pregnancies in which only one fetal sac was evident at 8 wk gestation produced similar results.http://www.IVFpredict.com) and iPhone/Android application (IVFpredict) for widespread use of our new prediction tool. These will acknowledge the current lack of external validation and will request provision of anonymised data  that in the coming years we will use as a means of external validation of this model. We have included full model details in Finally, we acknowledge lack of external validation of our model. Nonetheless, we believe that this model will improve the ability to stratify contemporary couples seeking IVF on the basis of low, moderate, or high likelihood of success. This is of particular relevance to couples willing to consider all therapeutic options, including use of donor oocytes, as there is a 5-fold difference in live birth between the lowest and highest decile of our prediction model. To facilitate validation of the model we are currently generating a free web-based prediction tool  cycles of IVF treatment in the United Kingdom.Rates of successful live birth outcome per IVF treatment cycle by year of treatment. (0.13 MB TIF)Click here for additional data file.Table S1N = 163,425 eligible participants.Description of cohort of IVF treatment rounds. (0.08 MB DOC)Click here for additional data file.Table S2N = 163,425 eligible; numbers for each predictor vary due to some missing data.Univariable associations of potential predictors for live birth following IVF. (0.09 MB DOC)Click here for additional data file.Table S3Associations of duration of infertility and source of oocyte with live birth, stratified by maternal age.(0.04 MB DOC)Click here for additional data file.Table S4Associations of causes of infertility and number of treatment cycles with live birth, stratified by use of ICSI.(0.03 MB DOC)Click here for additional data file.Table S5Associations of potential predictors for live birth following IVF with multiple pregnancies removed.(0.07 MB DOC)Click here for additional data file.Table S6Univariable associations of potential risk factors with preterm birth, low birth weight, and macrosomia amongst singleton births following IVF.(0.08 MB DOC)Click here for additional data file.Table S7Univariable and multivariable associations of potential risk factors with extreme preterm birth (<33 wk) amongst singleton births following IVF.(0.08 MB DOC)Click here for additional data file.Text S1Calculation of predictive probability of live birth after IVF according to Templeton model.(0.03 MB DOC)Click here for additional data file.Text S2Equation and tables for derivation of probability of live birth.(0.02 MB DOC)Click here for additional data file.


Birth Defects are a series of diseases that seriously affect children's health. Birth defects are generally caused by several interrelated factors. The aims of the article is to estimate the prevalence rate and types of birth defects in Inner Mongolia, China, to compare socio-demographic characteristics among the children with birth defects and to analyze the association between risk factors and birth defects.Data used in this study were obtained through baseline survey of Inner Mongolia Birth Defects Program, a population-based survey conducted from 2005 to 2008. The survey used cluster sampling method in all 12 administrative districts of Inner Mongolia. Sampling size is calculated according to local population size at a certain percentage. All live births, stillbirths and abortions born from October 2005 to September 2008, whose families lived in Inner Mongolia at least one year, were included. The cases of birth defects were diagnosed by the clinical doctors according to their experiences with further laboratory tests if needed. The inclusion criteria of the cases that had already dead were decided according to death records available at local cites. We calculated prevalence rate and 95% confidence intervals of different groups. Outcome variable was the occurrence of birth defects and associations between risk factors and birth defects were analyzed by using Poisson regression analysis.976 children with birth defects were diagnosed. The prevalence rate of birth defects was 156.1 per 10000 births (95%CI: 146.3-165.8). The prevalence rate of neural tube defect (20.1 per 10000 births) including anencephaly(6.9 per 10000), spina bifida (10.6 per 10000), and encephalocele (2.7 per 10000) was the highest, followed by congenital heart disease (17.1 per 10000). The relative risk (RR) for maternal age less than 25 was 2.22 . The RR of the ethnic Mongols was lower than Han Chinese . The RR of the third and second pregnancy was significantly higher than the first pregnancy while a slight difference between the second and the first pregnancy was also found. Alcohol drinking of mothers, familial inheritance and living area were also found to be related to the occurrence of the birth defects.Relatively higher birth defect rates were found in Inner Mongolia. This study found that maternal age less than 25, alcohol drinking, familiar inheritance, lower education level of mothers, times of pregnancies and living in rural areas may increase the risk of birth defects. Ethnic Mongols were less likely to have birth defects than Han Chinese. Birth defects are defined as a series of structural, functional and metabolic disorders. According to the literatures, birth defects are a major source of infant and child morbidity and mortality and single or multiple defects can be occurred in one or several organs of the children. In WestThe objectives of this study are to estimate the prevalence and types of birth defects in Inner Mongolia, to compare socio-demographic characteristics among the children with birth defects and to analyze the association between risk factors and birth defects.Data used in this study were obtained through baseline survey of Inner Mongolia Birth Defects Program, a population-based survey conducted from 2005 to 2008. 62544 births  from a general population of about 600,000 over a 3 year period were selected using cluster sampling method in all 12 administrative districts of Inner Mongolia. Sampling size is calculated according to local population size at a certain percentage. All live births, stillbirths and abortions were included in screening through house to house visits by clinical doctors. Medical records including prenatal diagnostic test results, labor records, clinic diagnostic results, pathology findings, physical examinations and artificial abortions of the patients who used to seek medications at local hospitals were used as references as part of the confirmations for final diagnosis.Two different questionnaires were developed. The first questionnaire included basic information of all eligible children such as socio-demographic factors of mothers, maternal unhealthy behaviors, history of familial inheritance, parental consanguinity, information at delivery and presence of birth defects at the time of visits. Families having a child with birth defects were asked to complete second questionnaire which contained questions on past diagnostic information at local hospitals, time duration until first diagnosis, past treatments and the types of defects.We classified birth defects according to International Classification of Diseases 9 (ICD9). Birth defects included anencephaly , spina bifida , encephalocele, congenital heart disease, total cleft lip (exclude median lip cleft), polydactylia (exclude bifurcate finger tip due to a broken nail), congenital hydrocephaly , external ear malformation, limb reduction defect, inguinal hernia, congenital hemangiomas and others. Neural tube defects included anencephaly, spina bifida, and encephalocele. Damage before and during birth was excluded from birth defects.For data entry, we used Epidata version 3.02  and for the statistical analysis, we used SPSS version 14.0 . Median and interquartile range was calculated for continuous variables. Prevalence rate and its 95% confidence intervals (95% CI) and chi-square test were used for showing the difference on different ethnicity groups, different living areas and other predictive variables. Occurrence of birth defects is the outcome variable. We used multivariate Poisson regression analysis to show the associations between possible risk factors and birth defects. Relative risk and its 95% confidence intervals were used for multivariate analysis. P-value less than or equal to 0.05 was considered as significance using 2-tailed test.Ethical clearance for the study was obtained from the Ethics and Research Committee of Inner Mongolia Medical College. A written informed consent was further obtained from the caregivers.Minimum and maximum age were 16 and 48  respectively. Out of 62443 births, there were 61992 live births and 451 stillbirths or abortions. Out of 976 birth defects we diagnosed in total, 164 cases were diagnosed before delivery, 575 cases were within one week after delivery, 139 cases were within one year, 44 cases were between one and two years, 29 cases were between two and three years, 5 cases were after 3 years and for 20 cases, time of the diagnosis could not be determined.Out of 976 children diagnosed as birth defects, 294 had died due to various reasons including birth defects (crude death rate: 30.12%), while number of death was 157 (crude death rate: 0.26%) among 61568 children without birth defects. Gender distribution of the birth defects was 54.9% (535 cases) in male, 38.7% in female (378 cases), 0.6% in ambiguous (6 cases), and gender of 57 cases (5.8%) could not be recognized.The prevalence rate of the birth defects was 156.1 per 10000 births (95% CI: 146.3-165.8); 124.6 per 10000 births (95% CI: 111.1-138.1) in urban areas and 179.4 per 10000 births (95% CI: 165.5-193.3) in rural areas (P < 0.05).χtrend2 = 147.650,P = 0.000). Maternal age was divided into four different age groups: <25 years; 25–29 years; 30–35 years, and >35 years. The highest prevalence rate occurred in >35 years group followed by <25 years group. There was no statistical difference between >35 years group and <25 years group. No statistically significant difference was found among different ethnic groups .TableTableTableWe defined variables as below: ethnicity , maternal age (age of mother at delivery), smoking (mothers smoked more than one cigarette per day during pregnancy), alcohol drinking , parental consanguinity (having same ancestor within 3 generations), familial inheritance history (birth defects found in family members).The risk of birth defects was lower among ethnic Mongols than Han Chinese . The risk was higher in rural areas than urban areas . There was a difference found between the maternal age groups < 25 years and >35 years . Compared to mothers with highest education level, the RR of birth defects among mothers with education level less than high school was 1.69 (95%CI: 1.58-1.82) while the RR among the high school graduates was 1.06 (95%CI: 0.95-1.18). Living areas were also significantly associated with birth defects in TableDrinking alcohol was associated significantly with the risk of birth defects while no association was found between smoking and birth defects. Families with familial history of birth defects were more likely to have birth defects  than those without family history. Times of pregnancy was also associated with the occurrence of birth defects in TableCompared to previous studies in China, this study had larger sample size to estimate prevalence rate and to explore the associations between possible risk factors and birth defects by controlling for other predictive variables respectively through multivariate analysis. The prevalence rate of birth defects in Inner Mongolia was 156.1 per 10000 births (95%CI: 146.3-165.8 per 10000), which is consistent with the prevalence rate in Gansu Province, western China (154.0 per 10000 births),12. The There might be several possible reasons for the higher risk of birth defects we observed in families living in rural areas. First, living, and especially working, in rural areas may bring people into contact with substances related to birth defects that are not present in urban areas. The results of one study indicated an association between birth defects and maternal agricultural work,17. SecoIn this study, we found no association between prenatal smoking habits of mothers and birth defects. The result is similar to a study showed that the offspring exposed to prenatal tobacco smoke had no increase in the prevalence of congenital malformations compared with non-exposed offspring in both crude and adjusted analyses.This study found that younger mothers aged <25 years had a greatly increased risk of birth defects in their offspring, which is consistent with a research in China. The autThe following is the limitations of the study: 1) it may could not include all cases with birth defect due to the limitations of diagnostic methods, for example, defects with insignificant symptoms are not likely to be found in early years of childhood; 2) perinatal death prior to diagnosis was also not included in this study.Through this study, it found lower risk of birth defects in Mongolian than Han Chinese and other ethnic groups, which need further research on the influence of genetics or cultural and environmental factors on birth defects among Mongols. This study also found that maternal age less than 25, alcohol drinking, familiar inheritance, lower education level of mothers, times of pregnancies and living in rural areas may increase the risk of birth defects. Moreover, some environmental factors such as underground water contamination due to mining activities, agriculture chemical exposure such as overdose using of pesticides etc. should be explored in the future. Based on the results which was obtained in this study, a few intervention activities are recommend as follows: 1) regular screening tests among pregnant women are needed at local health care sectors to decrease the rate of birth defects in Inner Mongolia; 2) in rural areas, health education programs among females at reproductive age and among pregnant women are also necessary to avoid exposures to preventable risk factors of birth defects; 3) health education for pregnant women at younger age both in rural and urban areas should be taken into consideration as part of the interventions at their first visit to the hospitals.The authors declare that there are no personal, organizational or financial conflicts of interest.XZ, SL, SW and XH participated in the planning, conception of the research questions, and design of the study. XZ, SL, XH and SG organized the investigation of the study and analyzed the data. XZ, KS, HY and ZY drafted the article and participated in interpreting data and critically revising the manuscript for important intellectual content. All authors read and approved the revised manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/12/125/prepub


The current decline in under-five mortality shows an increase in share of neonatal deaths. In order to address neonatal mortality and possibly identify areas of prevention and intervention, we studied causes of admission and cause-specific neonatal mortality in a neonatal care unit at Kilimanjaro Christian Medical Centre (KCMC) in Tanzania.A total of 5033 inborn neonates admitted to a neonatal care unit (NCU) from 2000 to 2010 registered at the KCMC Medical Birth Registry and neonatal registry were studied. Clinical diagnosis, gestational age, birth weight, Apgar score and date at admission and discharge were registered. Cause-specific of neonatal deaths were classified by modified Wigglesworth classification. Statistical analysis was performed in SPSS 18.0.Leading causes of admission were birth asphyxia (26.8%), prematurity (18.4%), risk of infection (16.9%), neonatal infection (15.4%), and birth weight above 4000 g (10.7%). Overall mortality was 10.7% (536 deaths). Leading single causes of death were birth asphyxia , prematurity , congenital malformations , and infections . Babies with birth weight below 2500 g constituted 29% of all admissions and 52.1% of all deaths. Except for congenital malformations, case fatality declined with increasing birth weight. Birth asphyxia was the most frequent cause of death in normal birth weight babies  and prematurity in low birth weight babies . The majority of deaths  occurred within 24 hours, and 490 (91.4%) within the first week.Birth asphyxia in normal birth weight babies and prematurity in low birth weight babies each accounted for one third of all deaths in this population. The high number of deaths attributable to birth asphyxia in normal birth weight babies suggests further studies to identify causal mechanisms. Strategies directed towards making obstetric and newborn care timely available with proper antenatal, maternal and newborn care support with regular training on resuscitation skills would improve child survival. The aim of the United Nations’ Millennium Development Goal 4 (MDG4) is to reduce under-five mortality worldwide to 30 deaths per 1000 live births by 2015. Globally, an estimate of 10.6 million children under five years died in 2000 [Worldwide, the most important single causes of neonatal deaths are preterm birth, birth asphyxia, sepsis and pneumonia ,5,6. ThiTanzania is among the countries with insufficient progress towards achieving the MDG4 showing slow decline in under-five mortality rate ,3,9, witGlobally, it has been estimated that ninety nine percent of neonatal deaths occur in developing country where also vital registration is limited . The UNIIdentification of cause-specific mortality in a particular setting is important to design interventions directed to improve neonatal survival. Therefore, in order to address neonatal mortality in Tanzania and possibly identify areas of prevention, we studied causes of neonatal admission and cause-specific neonatal mortality in a cohort of neonates delivered at the KCMC tertiary hospital and admitted to NCU.The primary study unit was the neonatal care unit (NCU) at the Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. As a tertiary and a referral hospital for the four regions in the Northern part of the country, the NCU at KCMC receives high risk babies delivered within the institution and referrals from other health facilities or from home. The NCU has bed capacity of 40 babies. The babies are nursed in locally made baby cots and there are heaters to keep the room as well as the babies warm. The unit has no mechanical ventilator or any continuous positive airway pressure machine. The babies receive oxygen through nasal prongs or face masks. There is no central oxygen supply; instead oxygen is usually stored in big cylinders. In addition, there are four portable oxygen concentrators. The midwives in the labour ward are responsible for the initial resuscitation of normal deliveries. Doctors from the paediatric department are called to the labour ward to attend the at risk pregnancies. Normal babies are put on the breast as soon as they recover from the birth trauma which is usually within the first four hours after delivery. Babies in the nursery rooms are either fed on expressed breast milk if the mothers are around or formula in the absence of the mothers. Feeding is given either through nasal gastric tube, syringe or cup and spoon. For neonates with feeding difficulties, parenteral feeding with either 10% or 5% dextrose depending on the gestational age is used.The neonatal care unit has 3 nursery rooms, one for preterm babies, one for term babies with non-infectious conditions and the third is reserved for bacterial as well as viral infections. Kangaroo mother care is being encouraged in the unit and a special room has been allocated for that purpose. Two other rooms are available for stable babies who are given to their mothers and to continue treatment under the supervision of the unit nurses, pending discharge when fully recovered.We have previously reported that approximately15% of the births within the KCMC hospital were transferred to neonatal care unit for admission . CriteriThis is a birth registry based cohort study. Neonates registered in the Medical Birth Registry and admitted to the neonatal care unit at KCMC, were included. The KCMC Medical Birth Registry was established in 1999 as collaboration between Kilimanjaro Christian Medical College, Tumaini University and the University of Bergen, Norway. The Medical Birth Registry and neonatal registry were officially established in July 2000.From July 2000 to October 2010, a total of 34087 births were registered in the birth registry, of which 5033 (14.8%) neonates were admitted to the neonatal care unit. These neonates formed our study population.Information from all mothers who delivered at KCMC was collected within the first 24 hours after delivery based on a standardized questionnaire as well as antenatal records. Detailed information collected for the Medical Birth Registry are described elsewhere .The neonatal registry form was recorded for all neonates who were transferred for admission in the NCU. The data collection form was administered by a trained paediatric nurse who worked in a neonatal care unit. The collection of information for neonates admitted to the NCU was done during admission and finalized after discharge or death. Information collected in the neonatal registry includes child’s ID-number, date of admission, reasons for admission, investigations done, management given, clinical details at discharge and death reports. The information collected from the Medical Birth Registry and neonatal registry were finally entered into a computerized database where they can be linked using the child’s ID-number.On arrival in the NCU, the baby is examined by a medical officer. Estimation of the gestational age is done using the Finnstrøm maturity score, which is a simple method for assessing maturity based on external characteristics. Tables for maturity score and transformation to gestational age are included in the KCMC Paediatric management schedule . The diaWe first coded clinical diagnoses independently depending on the presence of any diagnosis; a neonate having more than one diagnosis was recorded in different categories in order to study all causes of admission, case fatality and their contribution to total neonatal mortality. Case fatality was computed as number (percentage) of deaths within each clinical discharge diagnosis among admitted babies with the same condition.Secondly, the Wigglesworth classification with the revised decision tree ,18 with Data were analyzed using Statistical Package for Social Science (SPSS) program Version 18.0 for Window . Descriptive statistics measures such as mean, standard deviation, rate and proportions were calculated.th July 2010.The birth registry at Kilimanjaro Christian Medical Centre obtained ethical clearance from the Tanzania Ministry of Health, Institute of Science and Technology, from the Norwegian National ethics committee and from the Kilimanjaro Christian Medical College (KCM-College) research ethics committee in 1999. Informed consent was obtained from mothers prior to the interview. The protocol for this study was approved by KCM-College research ethics committee, with certificate no. 333 of 15A total of 5033 inborn neonates were admitted, of these 2806 (55.8%) were males, (Table The leading causes of admission were birth asphyxia 1351 (26.8%), prematurity 930 (18.4%), risk of infection 852 (16.9%), neonatal infection 776 (15.4%), and large for gestational age (birth weight above 4000 g) 538 (10.7%),  died. High case fatality was observed for babies with Respiratory Distress Syndrome (RDS), 52 (52.5%), congenital malformations 49 (43.6%), birth asphyxia 321 (23.8%) and prematurity 208 (22.4%), , prematurity 188 35.1%), congenital malformations 49 (9.0%), and infections 46 (8.6%),  for gestational age and birth weight for premature babies who died was 30.3 (3.3) weeks and 1342 (457) grams, respectively. On the other hand, the mean (SD) for babies who died due to birth asphyxia was 38.7 (3.0) weeks and 2843 (705) grams, respectively. Of the babies who died due to asphyxia 143 (58.4%) had 5-minute Apgar score below 5 whereas, 102 (41.6%) had 5-minute Apgar score above 7. The majority of deaths attributed to asphyxia  occurred in normal birth weight babies  died within the first 24 hours, and as many as 491 (91.6%) within the first week (Table 6.7% diedThe motive of our study was to identify morbidity and causes of neonatal death of inborn neonates admitted to a neonatal care unit at a tertiary hospital in Northern Tanzania. Our main results are largely consistent with the global pattern of mortality ,5, with Overall, 10.7% of the admitted neonates died in the neonatal period. This is similar to a study done in a regional referral hospital in Sudan where also only inborn neonates were included . Most otOur finding that birth asphyxia was the leading cause of death is consistent with a previous study from a university and tertiary care hospital in Tanzania . In contPrematurity was the second most important cause of death. Management of premature babies requires high specialized equipment, highly trained personnel and financial support ,30. In hSome specific and simple measures has been identified which could be implemented to reduce deaths related to low birth weight and preterm in low income countries ,34,35. TMortality due to infection was low compared to the global pattern as well as the pattern in low income countries ,16,23,25In a previous study from the same NCU where both inborn and outborn neonates were included one fifth of the deaths were due to infection . FurtherThe majority of women in low income countries do not access early ultrasound scan for screening of congenital malformation, and there are very few early terminations of pregnancies due to severe/fatal congenital malformations. Availability of management/surgery for neonates with severe congenital malformations is limited, and under the prevailing circumstances we suggest that few of these deaths could have been prevented.The majority of neonatal deaths occurred during the first day after admission and more than 90% within the first week of life. We found that birth asphyxia and prematurity were the major causes of death within the first 24 hours, whereas deaths related to infections were more frequent after first week. These results are similar to what has previously been observed ,34.This study used a large Medical Birth Registry with a complementary neonatal registry of neonates admitted to NCU where data are collected using standardized questionnaires. The data set contains a substantial number of neonates to be studied. All admitted neonates were given at least one discharge diagnosis and all information from the NCU could be linked to their information recorded in the birth registry. The modified Wigglesworth classification used to classify single causes of neonatal death was selected because it is simple to apply and since causes of death according to this classification have clear implications for clinical management. The classification gives the opportunity to identify areas of health care provision in need of prevention or improvement in management and care to improve neonatal survival. Since KCMC is a tertiary care hospital and included only inborn neonates, the results may not be generalized to all hospitals in Kilimanjaro or to the population.Birth asphyxia, prematurity and infection were the major single causes of neonatal morbidity and mortality. Birth asphyxia in normal birth weight babies and prematurity with low birth weight, each accounted for one third of all deaths, and some of these deaths may be preventable. First, strategies directed towards strengthening screening and identification of mothers at risk and early referral mechanisms for care and support is needed. Second, regular and continuous training of health personnel on essential newborn care to ensure basic knowledge on resuscitation skills and immediate actions needed for asphyxiated newborns should be strengthened. Care of premature babies should include in hospital kangaroo mother care for stable preterm and low birth weight babies, thermal care, feeding and nutritional support, as well as prevention and treatment of infections.Decline in neonatal mortality might have been hampered by insufficient feedback mechanisms within the hospital or between the hospital and peripheral health facilities where patients are referred from. Therefore, all deaths occurring in the hospital whether maternal or newborn should be reviewed and discussed between obstetricians and paediatricians; the cause identified, preventive measures worked out, and feedback given to all the staff involved within the institution as well as surrounding health facilities through existing outreach programs.Regular review of neonatal deaths using simple classifications within a particular setting will help to understand the magnitude of the problem and review the strategies for better improvement. Reviews should be directed towards identifying areas where screening, prevention and therapeutic interventions need to be strengthened.Efforts should be done to further develop registration systems in order to collect information that can be used to understand maternal and newborn health outcomes and serve as guidance for further preventive measures.The authors declare that they have no competing interests.BTM: Study design, methodology, data analysis and manuscript writing. RTL, RO, MJM, GK, AKD: Study design, methodology, manuscript writing. RTL and AKD approved the manuscript for final submission. All authors approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/12/116/prepub