In 2007, the Government of Pakistan introduced a new cadre of community midwives (CMWs) to address low skilled birth attendance rates in rural areas; this workforce is located in the private-sector. There are concerns about the effectiveness of the programme for increasing skilled birth attendance as previous experience from private-sector programmes has been sub-optimal. Indonesia first promoted private sector midwifery care, but the initiative failed to provide universal coverage and reduce maternal mortality rates.2 analyses were performed to assess variation in coverage of maternal health services between the two districts. Logistic regression models were developed to explore whether differentials in coverage between the two districts could be explained by differential levels of development and demand for skilled birth attendance. Mean cost of childbirth care by type of provider was also calculated.A clustered, stratified survey was conducted in the districts of Jhelum and Layyah, Punjab. A total of 1,457 women who gave birth in the 2 years prior to the survey were interviewed. χdai-attended birth. The CMWs were, however, having difficulty garnering community trust. The majority of women, when asked why they had not sought care from their neighbourhood CMW, cited a lack of trust in CMWs’ competency and that they wanted a different provider.Overall, 7.9% of women surveyed reported a CMW-attended birth. Women in Jhelum were six times more likely to report a CMW-attended birth than women in Layyah. The mean cost of a CMW-attended birth compared favourably with a The CMWs have yet to emerge as a significant maternity care provider in rural Punjab. Levels of overall community development determined uptake and hence coverage of CMW care. The CMWs were able to insert themselves into the maternal health marketplace in Jhelum because of an existing demand. A lower demand in Layyah meant there was less ‘space’ for the CMWs to enter the market. To ensure universal coverage, there is a need to revisit the strategy of introducing a new midwifery workforce in the private sector in contexts of low demand and marketing the benefits of skilled birth attendance. Pakistan, with a maternal mortality rate (MMR) of 260 deaths per 100,000 live births [dais, to their skilled care. They were supported with a small stipend for the first 2 years after their training while establishing their practices. To date, over 8,000 CMWs have been deployed [Drawing on this well-acknowledged evidence, the Government of Pakistan introduced a new cadre of skilled birth attendants, the Community Midwives (CMWs) . With thdeployed .Concerns about the effectiveness of the programme for increasing coverage of skilled birth attendance in rural areas remain, particularly as the CMWs are located in the private sector. Historically successful midwifery programmes, such as ones from Sweden, England, Sri Lanka, and Thailand, have largely situated midwives in the public sector. The concept of locating a midwifery workforce in the private sector was first introduced by Indonesia in the 1980s; between 1989 and 1996, Indonesia deployed 54,000 midwives in as many villages in the country [A large body of literature suggests that the Indonesian programme faltered because the midwives could not sustain their private practices after the expiration of their government contract -9. ThoseThe design of the Pakistani CMW programme is similar to the Indonesian midwifery initiative. Like the Indonesian programme, the Pakistani CMWs are located in the private sector . FurtherGiven the similarity of the Pakistani and Indonesian programmes, the question arises whether, 4 years after launch, the Pakistani CMW programme is expanding coverage of skilled birth attendance. Are there variations in uptake by demand for skilled birth attendants, which are in turn determined by overall levels of population education and socioeconomic status? Are CMW fees a factor in uptake of their services?The present paper will address these questions using data from the districts of Jhelum and Layyah in Punjab; Jhelum being a relatively well-developed district , and LayA cross-sectional, clustered, and stratified survey was conducted in two districts, Jhelum and Layyah, in the province of Punjab between November 2011 and July 2012. These districts were purposely selected because they were some of the first districts in which the programme was launched, they were safe enough for the researchers to collect data from, and span the range of socioeconomic development in Punjab. Historically, rain-fed agricultural practices in Jhelum could not sustain livelihoods, and men migrated to urban areas to find employment. This has led to overall higher levels of education and income levels in Jhelum. Layyah’s agriculture is based on a stable aqueduct irrigation system. The majority of residents are refugees settled here after migration from India in 1947, as well as a result of other natural disasters. The refugees were given small pieces of land that, because of the aqueduct, were sufficient to support families. It was postulated that these two districts would provide insight into the potential range of CMW coverage in the province, while acknowledging that the rates may not be representative of Punjab.The study population consisted of women aged 15–49, who had given birth in the 2 years prior to the survey, and lived in CMW-served catchment areas (study clusters). The 2 year limit was used because the first batch of CMWs graduated in 2008. A total of 1,457 women were surveyed, 747 in Jhelum and 710 in Layyah. This sample size was calculated using the Pakistan Demographic Health Survey 2007 data , which sThe sampling frame was drawn up using a three-stage stratified sample design. In the first stage, three out of four tehsils (sub-district units) in district Jhelum were randomly selected. All three tehsils in Layyah were selected. In the second stage, five union councils were randomly selected from each tehsil for a total of 30 union councils. If there was no CMW in a selected union council as indicated by programme records, it was replaced. In the third stage, two villages were randomly selected from each union council. However, if there were not enough eligible women in the selected village, a neighbouring village was included. This led to a total of 48 villages surveyed in Layyah and 69 villages in Jhelum. Within each selected village, a maximum of 22 women who gave birth in the 2 years prior to the survey were interviewed . Given t2 analyses were done to assess the sociodemographic characteristics of the sample population, use of ANC, type of ANC provider, type of birth attendant, and place of delivery stratified by district. Means were calculated for continuous data such as age, number of children, and cost of childbirth care. Logistic regression models using the forward selection approach were developed to find out if differentials in coverage between the two districts could be explained by differential levels of development and demand for skilled birth attendance.Data were analyzed using Stata 11.0 . Since lEthics approval was obtained from the University of Alberta Health Research Ethics Board and the National Bioethics Committee, Pakistan.The mean age of our sample of 1,457 rural Punjabi women in Jhelum and Layyah was 28 years; 38% had received no schooling, almost all were currently married, with an average of 2.9 children. Overall, women in district Jhelum had higher levels of education, with twice as many women having 10 years of schooling compared to Layyah (37% vs. 19%). Women in Jhelum were wealthier, with only 18% classified as poor, compared to 33% in Layyah. Table P <0.001). Of these 47%, the majority knew that the CMW provided childbirth services and nearly 80% had had contact with her in the context of an introductory home-visit or provision of antenatal, postnatal, and general medical care . In contrast, a physician-attended birth cost, on average, PKR 13,000 (US $125) and ranged from PKR 200–60,000 (US $1.9–577). There was, however, a vast variation in physician-attended births in the public and private sectors, costing PKR 7,800 (US $75) and PKR 15,670 (US $151), respectively. Overall, 64% of CMW clients had saved money for their childbirth.A CMW-attended birth cost a mean of PKR 2950  and have had discussions about emergency birth-preparedness . They were, however, less likely to have had an ultrasound compared to women who sought care from a physician .Respondents’ belief that CMWs lack competency is not supported by survey evidence. When comparing respondents’ reports of care received, those who had sought CMW services were as likely to receive elements of ANC at rates similar to those who reported care from physicians. These women were as likely to have a blood and urine test, receive two or more tetanus toxoid injections, and take iron supplements as women who received physician care. In fact, CMW clients were significantly more likely to have been weighed . Over 90% of them used a safe delivery kit. Use of gloves for vaginal examinations was universal.dai-attended birth. Regardless, the CMWs were continuing to struggle in garnering community trust. The majority of women, when asked why they had not sought care from their neighbourhood CMW, cited a lack of trust in their competency and that they wanted a different provider.The objective of this research was to assess whether the CMW programme, located in the private sector, is expanding coverage of skilled birth attendance, and if any variations in this coverage are associated with demand and cost of CMW care. CMW coverage rates were compared in two distinctly different contexts, the relatively well developed Jhelum and the less developed Layyah, to assess if there were differences in skilled birth attendance between the two districts, and if these variations are reflected in CMW uptake rates. We assumed use of a skilled birth attendant indicated demand for such a provider. The results show that, overall, CMWs have yet to emerge as a significant maternity care provider in rural Punjab. Only 7.9% of all women who gave birth in the 2 years after deployment of a CMW in their neighbourhood reported a  CMW-attended birth. There are, however, large differences in coverage rates between the two districts, with women in Jhelum six times more likely to report a CMW-attended birth. The results also showed that the mean cost of a CMW-attended birth compared favourably with a One possible reason for low CMW coverage could be that the programme is relatively new and the CMW cadre relatively unknown; our results support this, as only 47% of respondents reported they knew of the CMW in their area. At the same time, 47% is not necessarily a small number and is not reflected in the low use rate of 7.9%, suggesting there may be other reasons for women not using their services besides a lack of awareness of CMW presence.One of these reasons could be a lack of trust in CMWs competency, as this emerged as the most commonly cited reason for not seeking CMW services. The literature suggests trust and trustworthiness are key factors that determine the choice of a provider -23. Lackdais. Use of CMWs was much higher in Jhelum versus Layyah . Taking these two findings together suggests the possibility that a greater overall demand for skilled birth attendance in Jhelum provided CMWs greater ‘space’ to insert themselves into the maternal health marketplace. In contrast, the lower demand for skilled birth attendance in Layyah meant there was less ‘space’ for the CMWs to enter the market. Ultimately, as indicated by a companion qualitative study, the issue in Layyah was not which type of skilled birth attendant to use, but whether to use one at all, as dais remained trusted and preferred providers [A second possibility for low CMW coverage is a lack of demand for skilled birth attendance. Assuming use equated demand, a use rate of 86% suggests a high demand for skilled birth attendance in Jhelum. In contrast, only 52% of women in Layyah reported skilled birth attendance, with the remaining 48% using Another closely related finding supporting the above possibility is that there is no variation in the sociodemographic characteristics of women who reported CMW use. Women, irrespective of levels of education or asset quartiles, are equally likely to report CMW care. Yet Jhelum still had higher proportions of women using their services than did Layyah. One interpretation is that it was the overall high level of development in Jhelum that promoted CMW use. In this context, women’s low levels of schooling was less of a determinant of CMW use than the context in which she lived. The results suggest that contextual factors may be as or even more important than individual factors – that typically  dominate the maternal health care literature – on skilled birth attendance and inequities. These findings are new in the skilled birth attendant literature, but have been reported previously in family planning literature .dais. However, a companion qualitative study found that most CMWs were providing care to their relatives, who were charged nominal fees; they charged reasonably high fees, around PKR 6000 (US $58), for non-relatives [It can be postulated that another reason for low use of CMW services is their cost. As discussed above, the CMWs are located in the private sector. Previous qualitative  work suggests that CMWs’ fees are a deterrent for potential clients . Our surelatives . The aveTo summarize, the Pakistani CMWs have yet to emerge as a significant addition to the skilled birth attendant workforce in Pakistan. However, the variation in CMW coverage by development context of a district raises concerns that the CMWs' private sector location might translate into services only for those who can afford to pay while continuing to leave those women most vulnerable to maternal death unserved. This occurred in Indonesia and suggests a need to revisit the concept of private sector midwifery services.


The impact of prenatal exposure to cadmium (Cd) on birth outcomes is an area of concern. This study aimed to assess an impact of prenatal Cd exposure on birth outcomes in distinct coastal populations of South Africa.th, 50th, and 75th percentile for birth weight, birth length and head circumference, to test for a linear trend. Associations between natural log-transformed maternal CdB, size at birth and other factors were further evaluated using linear mixed-effects modelling with random intercepts.Cadmium was measured in maternal blood (CdB) (n = 641), cord blood and in maternal urine (n = 317). This investigation assessed the associations between CdB (non-transformed) and birth outcomes across the 25β = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB . Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts.The average gestational age in the total sample was 38 weeks; 47% of neonates were female, average birth weight was 3065 g and 11% were of low birth weight (< 2500 g). The geometric mean (GM) of the maternal CdB level was 0.25 μg/L . The cord blood Cd level was 0.27 μg/L  and urine (creatinine-corrected) Cd level was 0.27 μg/L . The CdB cord:maternal ratio in the sub-cohort was 1, suggesting that the placenta offers no protective mechanism to the foetus. An inverse association was found between CdB and the lower birth weight percentile in female neonates only (Significant inverse associations between prenatal Cd exposure and birth anthropometry were found in female neonates but not in male neonates, suggesting potential sex differences in the toxico-kinetics and toxico-dynamics of Cd. The impact of prenatal exposure to cadmium (Cd) on birth outcomes and childhood development is an area of concern and a subject of vigorous research, mainly in the northern hemisphere, while there continues to be a dearth of data from the southern hemisphere.Cadmium is a highly toxic pollutant present in the living environment that is detrimental to human health. The main source of Cd to humans is food, exposure to tobacco smoke, industrial activities and contaminated drugs and dietary supplements –3. Cd isCurrently, it is understood that the exposure to low doses of Cd from all sources may produce long-term health effects in humans . WorldwiCadmium is nephrotoxic and carcinogenic in humans and has been shown to be embryotoxic and teratogenic in animal models . The maiin vivo effects of oestrogen in the uterus, and mammary glands in rats, resulting in earlier onset of puberty, as well as affecting post-natal immune function. Some of these detrimental effects are already evident at low-level environmental exposures to Cd [It is now well understood that health risks from exposure to environmental pollutants are age and life stage related, and that prenatal exposures may have a direct impact not only on birth outcomes and early childhood development but also on health at all life stages of the individual . It has es to Cd –21.During the prenatal stage, Cd has not only the ability to accumulate in the placenta, but also the ability to permeate the placenta and interfere with the transport of various micronutrients to the foetus –24. ReceThe aim of this study was to investigate prenatal exposure to Cd from all sources, and its possible impact on birth outcomes in South African coastal populations, by measuring the maternal blood levels of Cd in a cohort of 641 women at the time of delivery. Furthermore, a sub-cohort of 317 women, from whom paired cord blood and maternal urine samples were collected, was assessed for a possible correlation between Cd levels in three biological parameters, viz. maternal blood, maternal urine and cord blood, which may be directly related to Cd exposure.This study is part of on-going multidisciplinary, multi-institutional research collaboration between South Africa and Norway—the Arctic Monitoring and Assessment Programme (AMAP)—that evaluates exposures and effects of persistent toxic substances (PTS) on reproductive health and birth outcomes in populations of the northern and southern hemispheres.A total of five sites were included in the study: three sites were situated along the Indian Ocean coast of the KwaZulu Natal (KZN) Province, and two sites were situated along the Atlantic Ocean coast of the Western Cape Province of South Africa .All three sites along the Indian Ocean coast can be defined as rural with varying degrees of agricultural activities. However, their geographical location may predispose them to environmental pollution emanating from mining and industrial activities (site 1); aluminium smelting, mining, coal terminals and ports (site 2); and small industrial activities (site 3). Along the Atlantic Ocean coast, one study site is the urban city of Cape Town, which is surrounded by commercial, industrial and port activities (site 4); and the second site is considered to be rural (site 5), where commercial agriculture and fishing activities dominate.Potential study candidates were recruited by a health worker on duty, from women who were admitted for delivery at the local maternity sections of public hospitals. A trained research assistant briefly explained the objectives of the study and distributed a detailed information sheet about the project. All women who agreed to participate signed an informed consent form and agreed to donate blood before delivery. Participants agreed to answer a socio-demographic questionnaire which also included the topics of diet, lifestyle, and health status. Participants also consented to access and use of hospital birth outcome data for research purposes. The socio-demographic questionnaire was not specifically designed for Cd exposure, but for exposure to environmental pollutants in general. The dietary part of the questionnaire recorded the intake frequency of various basic foods during pregnancy. After delivery, records from hospital files were extracted, including maternal and neonate characteristics such as weight, length and head circumference, gestational age, as well as any birth complications, if any. In total, 650 delivering women participated in the study, of which 641 women, who delivered singleton infants of gestation of more than 20 weeks, were included. Due to financial constraints, the collection of additional samples (pre-partum urine samples and post-partum cord blood samples) was limited to women residing in Sites 1, 2 and 3 (n = 317).From each woman, a volume of 10 ml of venous blood was collected before delivery into BD Vacutainer tube (10 ml capacity and containing EDTA). Participants from the sub-cohort (n = 317) also donated 30 ml of urine before delivery, and 10 ml of umbilical cord blood post-partum.The analyses for Cd content in whole blood and urine were performed using an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS) instrument (Agilent 7500ce ICP-MS with an Octopole Reaction System). Contamination-free vessels and procedures were used throughout, and validation of results was accomplished by including certified standards, as well as certified references quality controls, in the analyses.115In and 197Au as internal standards. Aliquots of each sample were analysed in triplicate. The detection limits  for Cd was 0.03μg/L. For quality assurance, two certified reference controls, viz. Seronorm ™Trace Elements  in whole blood (Levels 1 and 2), were analysed with every analytical run, at intervals between every 10 samples. Urine samples (1 ml volumes) were digested with 0.1 ml of 65% ultrapure nitric acid . An internal standard solution containing 72Ge, 115In and 197Au was added (50 μl) to all samples, reagent blanks, reference controls and calibration standards and made up to 5 ml (5 times sample dilution). Urinary Cd (CdU) levels were measured in ‘no gas’ acquisition mode and percentage recovery, when using certified standards (Seronorm Urine Blank and Lyphchek Level 1&2), was 108.8% and 111.5% for level 1 and 2, respectively.Briefly, the whole blood samples (0.5ml volumes) were digested with 1 ml nitric acid  at 90°C for 2 hours. After cooling, the internal standard was added and samples were diluted with water to a final volume of 7 ml. Cd was measured in ‘no gas’ acquisition mode with The sample analyses were conducted by the Johannesburg National Institute for Occupational Health (NIOH) laboratory, which participates in the Wadsworth Center—New York State Department of Health Proficiency testing scheme for whole blood and urine. The results obtained are consistently accepted with no indication of bias.Covariate information was obtained during the questionnaire-based interview and from medical records. Maternal weight and height were recorded at the hospital on admission. From the medical records, the following newborn characteristics were retrieved: birth weight (grams), birth length (cm), head circumference (cm) and gestational age (weeks). Preterm labour was defined as mothers giving birth at less than 37 weeks gestational age. Education was categorised as no education, completed primary school, completed secondary school and any level of tertiary education reached. Maternal tobacco smoking was defined as ever or never. Exposure to environmental tobacco smoke (ETS) was defined as exposure to tobacco smoke from smoking by others in the household. A binary classification was used for exposure to indoor smoke from the burning of fossil fuel  for the purpose of heating or cooking, separating women into those exposed to fossil fuel and those not exposed . Dietary questions relating to vine, root and leafy vegetable intake were assessed and classified as daily, at least once a week and seldom.nptrend in Stata) to test for linear trend. Linear mixed-effect models with random intercepts were used to identify significant predictors (p < 0.1) of natural logarithm—transformed blood Cd levels and to estimate the amount of variability in measured levels explained by the model. Potential explanatory variables were identified from questionnaire data that were associated with blood Cd levels with a p < 0.2 during univariate analyses: vegetable intake, smoking history, burning of fossil fuel, environmental tobacco smoke exposure, gestational age, parity, size at birth , and gender of the newborn. Model fit was compared using log likelihood and Akaike Information Criterion (AIC) statistics.The statistical analyses were performed using STATA . The distribution of Cd levels in maternal blood and urine and in cord blood, were skewed and were log transformed. Bivariate analyses between Cd exposure, sizes at birth and covariates were evaluated by Spearman’s correlation coefficient. The non-parametric Wilcoxon rank-sum (Mann-Whitney) and Kruskal-Wallis rank tests were used where appropriate, to make categorical comparisons of the maternal CdB distribution (n = 641) and demographic, dietary, and environmental characteristics. The 25th percentile (lowest quintile), 50th percentile (median quintile), and 75th percentile (highest quintile) were assessed for birth outcomes . Furthermore, associations between CdB (non-transformed) and size at birth across the quintiles were assessed using a non-parametric test , and from the relevant provincial Departments of Health. The sites along the Indian Ocean coast (sites 1 to 3) fall under the Provincial Department of Health of KwaZulu Natal, which issued ethical consent for each site and requested the CEOs of the respective hospitals to allow this research to take place. Each CEO confirmed that he/she allowed the research work to proceed. The sites along the Atlantic Ocean coast (sites 4 and 5) fall under the Western Cape Provincial Department of Health; identical procedures were followed in terms of obtaining consent for the study. Confidentiality was maintained by assigning identification numbers to all study participants. During the informed consent process, it was emphasised that participation was voluntary and could be withdrawn at any time.The background characteristics and Cd concentrations of the mothers are presented in 2. Approximately 26% of the women reported ever using tobacco, 40% reported exposure to environmental tobacco smoke in the household, and 37% burned fossil fuel for heating or cooking in their homes. p = 0.04). Additionally, 66 infants (11%) were considered to be of low birth weight.Maternal age ranged from 14 to 49 years, with the average being 25 years; approximately 44% of the women were primiparous. Their average BMI at admission was 29 kg/mth percentile was 0.26 μg/L, with an interquartile range of 0.04 μg/L to 3.73 μg/L. The GM of the cord Cd level was 0.27 μg/L  and the GM of the CdU level was 0.27 μg/L . Among the 317 mothers of the sub-cohort, the GM maternal CdB level was 0.26 μg/L . Since the ratio of maternal to cord CdB was found to be 1:1, we deduced that no placental protective effect was demonstrated.In the total study sample, the geometric mean (GM) of the maternal CdB level was 0.25 μg/L  and the 50rho = 0.08, p = 0.155) or between maternal CdU and cord Cd levels . A weak association was found between maternal CdB and CdU levels .There was no correlation between maternal CdB and cord Cd levels (p = 0.772). Mothers of infants who were born preterm had a higher GM for CdB levels (0.28 μg/L), compared to the mothers of infants born at term (0.24 μg/L); however this finding was not significant (p = 0.337).Maternal CdB levels did not differ between multiparous  and primiparous mothers  at delivery, by smoking history, ETS exposure and burning of fossil fuel is described in p < 0.001) and mothers exposed to ETS in their household . Interestingly, mothers who burned fossil fuel in their household for heating or cooking were found to have significantly lower maternal CdB levels .Maternal CdB levels were significantly higher among mothers who reported ever having smoked . Mothers who seldom ate root vegetables had significantly higher CdB levels  than mothers who ate root vegetables once a week  or daily . Maternal CdB levels did not differ between mothers who seldom ate leafy vegetables (0.36 μg/L) and mothers who ate leafy vegetables at least once a week  or daily .Mothers who consumed vine vegetables at least once a day had significantly higher blood Cd levels  than mothers who seldom consumed vine vegetables  or consumed vine vegetables once a week . There was no trend found across birth length  or head circumference quintiles .Mean CdB levels were highest at the 25The association between maternal CdB levels and size at birth by gender was also investigated. p-value for trend, p < 0.001). No significant trend was shown by birth length  or head circumference . In male infants, no significant trend was shown by birth weight , birth length  or head circumference .For female infants, the highest mean maternal CdB levels were reported for the lowest birth weight percentile. Specifically, maternal CdB levels decreased as birth weight increased  were associated with lower natural log transformed maternal CdB levels  and root vegetables  daily were associated with lower natural log transformed maternal CdB levels. As expected, mothers who reported ever having smoked were associated with higher natural log transformed maternal CdB levels .Mothers who consumed vine . Also, mothers who consumed vine vegetables daily had decreased CdB levels, thereby demonstrating a potential protective effect . In both male and female newborn cohorts, maternal smoking was associated with an elevation in natural log transformed maternal CdB levels.In the stratified analyses, the inverse association between birth weight and maternal CdB was shown only for female newborns   and the When evaluating placental permeability with regard to CdB, the placenta did not appear to function as an efficient barrier against Cd passage, as previously reported , 32–34. The current study did not find correlations between maternal CdB levels and cord CdB levels, and a weak association was found between maternal CdB levels and creatinine-corrected urine CdU levels. In the majority of the studies performed in the general and occupationally exposed population, as well as in some studies on pregnant women, the CdU level has been used as the “biomarker” of choice for Cd exposure. The findings from this study suggest that more research is required to identify the most suitable biomarker for Cd exposure in humans . The uriIn line with the latest research on gender related differences in exposure and the resulting health effects caused by metals, the association between maternal Cd concentration and size of neonates at birth, by gender, was investigated . Among fProtective effects of diet were found for all infants of mothers who consumed vine and root vegetables daily, suggesting a low Cd content in agricultural soil or an inability of these vegetables to absorb Cd in the coastal geographical area under investigation, as most of the women reported growing their own vegetables.Although, our study was performed on a large cohort of women, there are number of limitations which need to be considered. The first is a recall bias in dietary intake. Secondly, due to financial constraints, the collection of additional samples (pre-partum urine samples and post-partum cord blood samples) were limited to women residing along Indian Ocean coast only, which might have introduced some bias. It also appears that women in the sites along the Indian Ocean coast may have under reported their smoking habits, and since cotinine was not measured it is impossible to verify the answers given in their socio-demographic questionnaires.The investigation was performed on a fairly large sample size of 641 women who resided in five geographically distinct coastal sites of South Africa. The main strength of this study is the measurement of Cd levels in three biological parameters, viz. in the maternal blood and in maternal urine and cord blood samples, in the case of the sub-cohort of women. A significant inverse association was found between prenatal Cd exposure and birth weight in female neonates, but none in male infants, confirming the potential for sex response differences to Cd exposure. Of concern is the fact that low birth weight was evident at relatively low Cd concentrations in all three biological parameters, especially as it has been suggested that low-level environmental Cd exposure in children may be associated with adverse neurodevelopmental outcomes.Based on these findings, the authors recommend that Cd levels be more thoroughly investigated across pregnancy and post-partum, so as to identify prevention methods for foetal Cd exposure, from a public health perspective.S1 Results(DOCX)Click here for additional data file.


Transcutaneous bilirubin (TcB) nomograms have been developed for different populations. However, the TcB level, rate of rise and peak varies among countries and ethnicities. The aim of this study was to establish an hour-specific TcB nomogram for healthy term and late preterm Mongolian neonates during the first 144 h after birth. A total of 5084 TcB measurements from 1297 healthy neonates  were obtained from October 2012 to October 2013. All measurements were performed using the Jaundice Meter, the JM-103 at 6 to 144 postnatal hours. Mongolian infants had the following characteristics: 27.1 % were delivered by cesarean section, 17.8 % had a birth weight >4000 g, and >90 % were being breastfed. TcB percentiles for each designated time point were calculated for the development of an hour-specific nomogram. TcB levels increased most rapidly in the first 24 h and less rapidly from 24 to 78 h, reaching a plateau after 78 h for the 50th percentile. TcB levels of Mongolian neonates for each time point were higher than those of previous studies.Conclusion: The higher values of the TcB nomogram for Mongolian neonates may be due to their Asian ethnicity and exclusive breastfeeding. Neonatal hyperbilirubinemia and neurological sequelae resulting from kernicterus pose a serious medical burden in both developing and developed countries , 16, 23.TcB nomogram is a useful tool for neonatal hyperbilirubinemia screening . HoweverThe aim of this study was to create an hour-specific TcB nomogram for healthy Mongolian neonates, which was achieved by obtaining TcB measurements in the first 144 h after birth.This was a prospective cohort study at the National Center for Maternal and Child Health (NCMCH), a tertiary care hospital in Ulaanbaatar, Mongolia. Neonates who were eligible for enrollment were healthy newborns ≥35 weeks of gestation with a birth weight ≥2000 g who were delivered in the hospital on a weekday (from Monday to Friday morning) and whose address were in the Bayangol district. Exclusion criteria included the following: infants with birth asphyxia, respiratory distress, NICU admission, congenital infection, Rh isoimmunization, jaundice within 24 h of birth, skin infection, congenital spinal anomaly, those with no TcB measurement, and cases with missing information. The study was carried out from October 15, 2012 to October 4, 2013 but was temporarily suspended between June 28 and August 2, 2013 when the maternity unit was closed for renovation. Perinatal information on the mother and infant were extracted from their medical charts including sex, gestational age, birth weight, mode of delivery, duration of hospitalization, maternal age, parity, gravidity, maternal blood type, family history of siblings, and feeding type before and after discharge.This study was approved by the NCMCH ethics committee in Mongolia and the National Center for Global Health and Medicine (NCGM) human investigation ethics committee in Japan, in accordance with the Declaration of Helsinki. Informed consent was obtained from all individual participants (mothers of the infants) included in the study.TcB measurements were performed between 9 am and 5 pm twice daily (once in the morning and once in evening) from Monday to Friday. The Jaundice Meter JM-103  was used by properly trained pediatricians or a research technician to measure TcB. The operation of the JM-103 and its measurement technique have been described previously [TcB measurements obtained at 6 ± 2 h intervals up to 144 h were examined , 18. TcBThe characteristics of mothers and children are presented as percentages for binary and categorical data, and as means and standard deviations for continuous data. The data analysis was performed by using SPSS 15.0 for Windows .TcB percentiles  were calculated for each designated time. A TcB nomogram with smoothed percentile curves for the period 6–144 postnatal hours was prepared using Microsoft Excel 2010 .Of 1846 live births in NCMCH during the study period, 549 neonates did not meet the enrollment criteria  for the time period 6–144 postnatal hours is presented in Fig. We created an hour-specific TcB nomogram for the first 144 h after birth for Mongolian healthy term and late preterm neonates. The characteristics of this group of Mongolian neonates included delivery by cesarean section in 26.9 % of cases and exclusive breastfeeding in >90 %. The TcB values and rate of rise at each designated time point resulted in a TcB nomogram with higher values than those reported for other countries and ethnicities in previous studies. This result indicates that this group might have risk factors and a higher likelihood of developing neonatal hyperbilirubinemia.Many TcB nomogram studies have been performed in North America, Europe, and Asia in different groups , 25, 28 This prospective cohort study was a tertiary hospital-based study that enrolled neonates from one district, and TcB measurements were done either in the maternity unit or in the outpatient clinic . Our stuThis study has several limitations. First, there were insufficient numbers of TcB measurements at the follow-up visit on day 3–6, only one to two measurements. Second, the designated times for TcB measurements were difficult to establish, leading to the omission of a certain number of TcB measurements. However, it was impossible to fix a designated TcB measurement time for each neonate in ordinary practice. Third, the glucose-6-phosphate dehydrogenase (G6PD) and direct Coombs test are not routinely performed in prenatal care screening in Mongolia so G6PD deficiency and ABO incompatibility could not be ruled out in this group. Fourth, cephalohematoma, a risk factor for hyperbilirubinemia, might be increased, considering the high percentage of vaginal deliveries and heavy infants (17.8 % had birth weight >4000 g) , 24. AltThe findings in this study contribute to improving appropriate diagnosis and treatment of neonatal hyperbilirubinemia, and might reduce the incidence of neurological impairment in this high-risk ethnic group.We provide data on TcB levels for the first 144 postnatal hours that were derived from a group of Mongolian term and late preterm neonates. The higher values of the TcB nomogram derived from Mongolian neonates may be due to their Asian ethnicity and exclusive breastfeeding.


Dear SirThe baby was born to a 24-year-old primigravida mother by cesarean section at 36 week gestation and weighed 2420 grams. Antenatal scan at 32 week gestation showed dilated bowel loops and polyhydramnios (Amniotic fluid index: 32 cm) suggestive of intestinal obstruction. He developed respiratory distress soon after birth and was referred to our unit. On examination, the baby had respiratory distress with RR of 72/min. and sub costal retractions. Abdomen was distended at birth and baby had 120 ml of bilious aspirate in the first 14 hours of life. X-ray of abdomen showed dilated proximal bowel loops with absence of gas in distal bowel loops suggestive of intestinal obstruction. A provisional diagnosis of intestinal atresia was made. Laparotomy showed duplication cyst measuring 6 cm in diameter along the antimesenteric border involving proximal ileum and malrotation of small bowel  Duplication cyst along with adjoining portion of ileum measuring 13.5 cm was resected and end to end anastomosis was done. Ladd’s procedure was done for malrotation. Histopathology showed the cyst attached to serosal aspect on the anti-mesenteric side without communication with ileum, but had a common muscular wall lined with simple columnar epithelium consistent with ileal duplication cyst. Baby was fed from the 7th day and was discharged uneventfully on the 14th postoperative day. Enteric duplication cysts (EDCs) are very rare with an estimated incidence of 1 in 4500 births. EDCs may be suspected by sonographic demonstration of an intra-abdominal cystic mass in the second or third trimester of gestation. The differential diagnosis of antenatal intra-abdominal cysts includes ovarian cysts, enteric duplication cysts, renal cysts, choledochal cysts, hepatic cysts, mesenteric or omental cysts and dilated bowel loops of intestinal atresia.[1] Sonographic findings highly suggestive of an intestinal origin of the cyst are peristaltic muscular contractions of the cyst wall, double layered wall and intimate contact with the mesenteric border.[1-3] Prenatal diagnosis of EDC is often difficult and sonography identifies 20 to 30% of lesions. In our case, antenatal scan showed dilated bowel loops and polyhydramnios suggestive of intestinal obstruction but duplication cyst was not noticed.EDCs can give rise to symptoms at any age but usually present during infancy with varied clinical presentation, depending on the location, size and the presence of heterotopic gastric mucosa. [1-3] Heterotopic gastric mucosa can cause bleeding or perforation by peptic ulceration. Enteric duplications can serve as the focal point for volvulus or intussusceptions.[4] EDC can be asymptomatic and the diagnosis is often made incidentally during a surgical procedure. Resection of the duplication cyst along with the adjacent bowel is suggested owing to the possibility of malignant changes and the risk of gastrointestinal obstruction, ulceration and hemorrhage due to ectopic gastric mucosa.[4] Large duplications, however, are difficult to resect due to the risk of short-bowel syndrome. Mucosal stripping offers a good surgical option in these cases, eliminating the possibility of subsequent peptic ulceration or carcinogenesis. According to the proposed vascular classification, resection of the duplication cyst without the adjacent bowel seems possible in some cases.[4] In our case, resection of EDC along with adjacent portion of ileum was performed as it was not possible to separate the ileum from the duplication cyst.Source of Support: NilConflict of Interest: None


Objective: Maternal hypovitaminosis D may impair fetal growth and cause adverse pregnancy outcomes including intrauterine growth restriction and neonatal low birth weight. The aim of this study is to evaluate the relationship between maternal vitamin D status and neonate’s birth weight. Materials and methods: A cross-sectional, descriptive analytical study was carried out in the nursery ward of 2 hospitals (Tehran-Iran) during one year (January 2011- January 2012). One hundred and two neonates were categorized into two groups, neonates with birth weight< 2500 gr (n=52) and neonates with birth weight>2500 gr (n = 50). Data regarding medical history, physical examination and anthropometric measurements of neonates were noted in a questionnaire. Birth time blood samples of their mothers were analyzed for serum 25-(OH)-vitamin D by ELISA method. Maternal vitamin D status was compared in two groups.Results: Mean maternal vitamin D (vit D) level was 31.46 nmol/L. Forty eight percent of mothers had vitamin D deficiency, 27.5% had vit D insufficiency and 24.5% were normal. Mean maternal vitamin D level of LBW neonates was lower than other group; 25.05 vs. 38.13 (p = 0.001). All mothers of neonates with head circumference ≤ 33 cm also had vitamin D deficiency (p = 0.007).Conclusion: Maternal Vitamin D deficiency may increase the risk of low birth weight neonate and modifying maternal nutrition behavior and their vit D level could be beneficial on pregnancy outcome. Low birth weight (LBW) refers to term or preterm neonates with birth weight < 2500 gr. These neonates may be small for gestational age or have intrauterine growth restriction. Mortality rate in such neonates is 40 times more than those with normal weight . Some inHigh Prevalence of vit D deficiency (about a billion) has been seen among people all over the world . DespiteA cross-sectional, descriptive analytical study was carried out in the nursery ward of AliAsghar and Akbarabadi hospitals; 2 tertiary referral centers and also teaching hospitals affiliated to Iran University of Medical Sciences (Tehran-Iran) during a year (1 January 2011-1 January 2012). Neonatal physical examination and anthropometric assessments were done and recorded. The target population included term- normal birth weight > 2500 gr), term neonates with birth weight < 2500 gr and their mothers . The exclusion criteria included mothers with preeclampsia, eclampsia, postpartum hemorrhage, insulin dependent diabetes mellitus, systemic and chronic disease, hematologic disorders, medication, twin pregnancy, drug abuse, and neonates with congenital malformation and infection (TORCH). A group of expert neonatologist (n = 5) designed a questionnaire based on review literatures, and then pretested it for 10 cases. Finally reliability and validity of the questionnaire have proved (Chronbakh α = 0.80). An expert nurse filled out questionnaires and recorded neonatal gender, birth weight and height, gestational age, mode of delivery, mother’s age, parity, race and ethnicity, mother’s education and clinical vit D deficiency symptoms. Immediately after birth, 5 ml of mother’s blood was collected, labeled and sent to laboratory to assay serum 25- (OH)-vit D level by 25-Hydroxy Vitamin D Enzyme immunoassay method . Depending on mothers’ 25- (OH)-vit D level, all mothers were categorized in deficient (< 25 nmol/L), insufficient (25-50 nmol/L), normal (> 50nmol/L) and toxic level (> 250nmol/L)   according Helsinki declaration. All participants gave informed consent before entering the study. Our gathered data were confidential and no extra cost was constrained on our participants.Among 107 mothers, 5 mothers were excluded because of mothers' refusal, preeclampsia and insulin dependent diabetes mellitus.Mean maternal serum vit D level in all 102 mothers with mean age 26.20 years and mean gestational age 38.73 weeks, was 31.46 nmol/L (4.3- 94 nmol/L). Some demographic characteristics are shown in Of all mothers, 48% had vit D deficiency, 27.5% had vit D insufficiency and 24.5% were in normal range. Mean maternal serum vit D level in those with LBW newborns was significantly lower than in those with normal birth weight newborns (p=0.001). Maternal serum vit D status in both groups are demonstrated in < 33cm were born to mothers with vit D deficiency in compare to 39 cases with HC > 33Cm, of which 20 were vit D deficient, 15 insufficient and 4 sufficient. Chi Square analysis signified the reverse relationship between maternal vit D deficiency and head circumference (p = 0.007).All 13 neonates with head circumference (HC)Maternal vit D deficiency in neonates who were born by NVD, were lower than C/S delivered babies (p = 0.027).There were no significant statistical differences in maternal vit D level between neonates with height ≤ 47 cm and neonates with height > 47 .Mean maternal age was higher in vit D deficient mothers based on ANOVA Analysis (p = 0.031). However, based on Logistic regression test, maternal serum vit D deficiency caused neonatal LBW  regardless of mothers’ age, and old age had no effect on both neonates’ birth weight (P = 0.44) or maternal serum vit D level (p = 0.8).Regarding ethnicity, prevalence of vit D deficiency in Lor, Kord and Turk mothers was significantly higher than that in Fars mothers (p = 0.039).There were no relationship between mother's parity or education and maternal vit D deficiency  respectively.2+ homeostasis and parathyroid hormone. Few studies have been conducted to detect vitamin D status in mothers in Iran. In recent study, nearly half of our mothers had vit D deficiency. In another study which has performed in our country, vit D deficiency was found to have widespread incidence, especially in rural women (61.1%) in compare to the urban ones (46.2%)  . Hypovit (46.2%) . We found a significant correlation between LBW and maternal vit D deficiency. Our finding was compatible with study from Bodnar et al. They showed a positive relationship between vit D deficiency in white mothers and neonatal LBW, however; this finding was not seen in black mothers . Morley Safety of vit D supplements and fortification have been proved by some articles. Mothers using vitamin D supplementation (400-4000 IU/day) in 12-16 weeks showed lower preterm risks . It seemShin et al. have suggested that inadequate vit D intake during pregnancy is related to low neonatal birth weight and shorter infant height , 13, howLow 25-(OH)-vit D level could be correlated with some mothers' diseases such as preterm labor, gestational diabetes mellitus and preeclampsia that affect on fetal growth -11, but <33cm. In consistent to our results, Aghajafari et al. indicated a significant association between small for gestational age infants  and mother's vit D insufficiency (We saw that mothers with vit D deficiency gave birth neonates with head circumference (HC) ficiency . On the ficiency .Although a significant difference was found between the mode of delivery and mother’s vit D status, our finding was against investigationfrom Dror et al. .No relationship was found between mother’s education and the level of vit D, unlike the Scholl et al. study, in which reluctance to use prenatal multivitamins and other dietary supplements was reported among illiterate women .In addition, some studies emphasize that the ethnicity and race both have a role in vit D deficiency in women and neonates . In our Although our study did not evaluate the effects of maternal nutrition, supplemental intake and the amount of sunlight exposure on the vit D status, we speculate that these factors should be considered in future studies.In conclusion as high prevalence of vit D deficiency has been seen among women especially in developing countries, this study shows that neonatal low birth weight (LBW) could be related to maternal vitamin D deficiency. Modifying maternal nutrition behavior and vit D level could be beneficial on prevention of low birth weight, however more research in this field seems contribute to an improvement in maternal and neonatal health.


Previous studies have shown that adverse conditions during fetal and early life are associated with lower performance on neurocognitive tests in childhood, adolescence and adult life. There is, however, a paucity in studies investigating these associations into old age. The aim was to investigate the impact of early life factors on cognitive function in old age by taking advantage of the potential for a linkage between a community survey and historical birth records.A historical cohort study employing a linkage between a community survey of people aged 72–74 years with the participants’ birth records (n=346). Early life factors included anthropometric measures taken at birth, birth complications, parental socioeconomic status, and maternal health status. The main outcome was a z-scored composite cognitive score, based on test scores from Kendrick Object Learning Test, Trail Making Test A, a modified version of the Digit Symbol Test, Block Design, a modified version of Mini-Mental State Examination and an abridged version of the Controlled Oral Word Association Test (COWAT). The separate cognitive tests were also individually analysed in relation to measures identified at birth.Higher parental socioeconomic status  was associated with a higher value on the composite cognitive score  and higher Digit Symbol and Trail Making Test A performance. Higher head circumference at birth was associated with higher COWAT and Trail Making Test A performance. Both higher parental SES and head circumference at birth predicted cognitive function in old age independently of each other. There were no other consistent associations.In general we found little evidence for a substantial role of early life factors on late-life cognitive function. However, there was some evidence for an association with parental SES status and head circumference on certain cognitive domains. Age-associated cognitive decline and mild cognitive impairment in old age is a major public health challenge  and lower performance on tests of neurocognitive function in childhood, adolescence and adult life  which has been described in more detail elsewhere , date of birth, place of birth and parents’ names (when available) of HUSK participants were retrieved. This information was used to trace the participants born in Bergen to the birth records from the public maternity ward (“Fødestiftelsen i Bergen”) presently stored at the Regional State Archives of Bergen. In the second decade of the 20th century, about one quarter of all births in the Bergen area took place in the official maternity ward . The proportion of deliveries taking place at hospitals increased steeply when the new Women’s Clinic (“Kvinneklinikken”) was inaugurated in 1926, replacing the old maternity ward. The pertinent birth records for the present study were those detailing births between 1st of January 1925 and 31st of December 1927, and these records have been employed previously in a similar study design : birth weight (kg), birth length (cm), head circumference (cm) at birth, ponderal index , mother’s pelvic size . The following binary variables were derived from individual free text fields: any recorded disease in the mother (yes/no), family history of coronary heart disease (yes/no) and tuberculosis , the state of mother’s teeth (poor/good), mother’s condition after birth (poor/good), complications during birth  and episiotomy, uterine rupture, discoloured amniotic fluid, abnormal fetal souffle and placenta praevia; yes/no), mother’s general somatic state at discharge (poor/good), marital status (married/unmarried), socioeconomic status , and type of payment for the hospital stay .HUSK included a cognitive test battery consisting of six tests. The cognitive tests are in wide use internationally and have been well validated, including the Norwegian versions of MMSE and KOLT Kendrick . Two assThe Kendrick Object Learning Test is designed to assess episodic memory performance Kendrick . The maxThe Trail Making Test A is a test of visual conceptual and visuomotor tracking Reitan . The tesThe modified version of the Digit Symbol Test measures perceptual and psychomotor speed, focused attention and visuomotor coordination Wechsler . In the The Block Design test investigates visuospatial and motor skills Wechsler . In the The Modified version of the Mini-Mental State Examination is designed to test various aspects of cognitive function, including orientation, instant recall and memory  composite cognitive scale was constructed by summing the separate standardized scores for each of the tests. The composite cognitive score constitutes the main outcome in this study.During the late 19th century and early 20th century, Bergen city expanded geographically, and went from a semi-rural city to a city with more modern characteristics. Primary industry which had dominated gave way for an expanding secondary and tertiary industry  and participants without . Level of educational attainment was divided into “compulsory only” (up to ten years) and “post-compulsory” (11 years or more), while general health was divided into “poor” and “good”. As APOE gentotype has been associated with cognitive function  a power analysis indicated that we would be able to detect a small to medium effect size for continuous outcomes (a correlation of 0.13), and mean differences (Cohen’s d of 0.35) at a power of 80%  given our sample size . The permission to collect and store the data from HUSK was given by the Norwegian Data Inspectorate. All participation in HUSK was voluntary, and all potential participants received written information about the project before they met for examination. The participants gave their written statements of informed consent, including the specific consents to use information from HUSK in health research and to link this information with other relevant data sources. This specific study was reviewed and approved by REC.No systematic differences were found between the HUSK participants we were able to trace, compared to the rest of the participants with regards to gender, educational attainment, self-reported health, or the cognitive tests Table . The samOut of the 136 crude associations investigated, only 10 7.4%) were significant at α=0.05 (Tables % were siIn this study investigating the association between the environment present around birth and cognition in old age, we found little evidence to support a substantial influence. We only found weak support for any anthropometric measures obtained at birth being predictive of cognitive function in old age. Specifically, only head circumference was associated with a better performance on COWAT and TMA in old age in the unadjusted model. This is contradictory to a previous paper which found no association between head circumference at birth and adult cognitive function, but a positive association between adult head circumference and adult cognitive function (Gale et al. Important strengths of this study included access to birth records from the 1920s and the possibility to link this information to a population-based health survey in the late 1990s, enabling a 72–74 year follow-up. Data sources for both exposure and outcome status contained detailed information, and the gathering of information is unlikely to be biased in any particular direction. Considering the birth records, these were used at the time in the education of midwives under the supervision of the head physician with a high level of attention to quality, and included detailed anthropometric measures, as well as information about maternal health and circumstances, the birth process and the early post-natal period. Another strength, is that the cognitive examination part of the HUSK study included cognitive tests investigating several different cognitive domains ranging from episodic memory, executive function visuospatial and motor skills and verbal fluency.A key limitation is that a relatively small proportion of the HUSK sample could be traced to their birth records. There are several potential reasons for this: the birth records were only available for a subgroup as not everyone who participated in HUSK was born in the Bergen area, and some were born at home or at other hospitals. Based on a conservative estimate, at least one-third of the HUSK sample would not be within the catchment area of the public maternity ward at the time of birth. The sample that was traced was representative of the participants in the HUSK cognitive examination. The results of the analysis are therefore likely to generalize to others of this generation and residence. However, it cannot be assumed that the traced participants were representative of people born in the location from which the early life records were taken. In particular, the representativeness of the birth cohort in HUSK might well have been influenced by intervening migration and survival effects because of the long follow-up. Healthy survivor effects (Baillargeon & Wilkinson We found little evidence to support a substantial association between intrauterine or birth environment and cognitive function in old age in general. The only anthropometric measure which to a certain degree predicted cognition in old age was head circumference, and parental SES was the only exposure which was associated with the composite cognitive score. Both a higher head circumference and SES seemed to predict a higher cognitive function in old age independently of each other. One potential explanation for this is that early SES and head circumference are predictors of two different aspects of later cognitive function Stern . The assThe lack of a substantial association between intrauterine or birth environment and cognitive function in old age, may be also be a reflection of a diminished impact of these early factors as other influences comes into play across the lifespan (Zhang et al. In conclusion, we found little evidence to support a substantial association between intrauterine or birth environment and cognitive function in old age in general. There were, however, some findings relating socioeconomic status and head circumference at birth and cognitive functioning in old age that warrants further investigation.


Exposure to air pollution has adverse effects on cardiopulmonary health of adults. Exposure to air pollution in pregnancy may affect foetal development. However, the evidence of such effect remains inconsistent. We investigated the effects of exposure to air pollution during pregnancy on birth outcomes.2 exposure and birth outcomes.This study, based within the Norwegian Mother and Child Cohort Study (MoBa), includes 17,533 participants living in the two largest cities in Norway: Oslo and Bergen, and their two surrounding counties: Akershus and Hordaland. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy using continuous monitoring station data. Birth outcomes were birth weight, low birth weight, gestational age, and preterm delivery obtained from the Medical Birth Registry of Norway. Information on lifestyle factors was collected from MoBa questionnaires completed by mothers during pregnancy. Linear and logistic regression models were used to analyse the associations between pregnancy NO2 and birth weight −43.6 (95%CI −55.8 to −31.5) g per 10 μg/m3 NO2. However, after adjusting for either area or the combination of parity and maternal weight, no substantive effects of air pollution exposure were evident.We found a statistically significant negative association between pregnancy exposure to NOExposure to air pollution during pregnancy was associated with decrease in birth weight, but area-related and lifestyle factors attenuated this association. We found no statistically significant associations of air pollution exposure with gestational age, low birth weight or preterm delivery.The online version of this article (doi:10.1186/s13690-016-0138-8) contains supplementary material, which is available to authorized users. The ass2 for the specific areas of Norway that we studied: two city areas (Oslo and Bergen) and their two surrounding counties . The selected areas represent the most populated areas in Norway and also include the territories with highest levels of ambient air pollution. Each of these four areas has different land use practices, road network density, industrial activities and landscape specifics. To our knowledge, previously the associations of modelled air pollution exposure with pregnancy outcomes were studied in Norway only in Oslo [2.5 with an increased risk of low birthweight at term but no significant decrease in birth weight [With the development of new methods, epidemiologic studies have been able to provide more individualized exposure assessment by using dispersion or land use regression (LUR) models for estimating air pollution exposure at residential addresses. In this paper we built LUR models for traffic-related air pollutant NO in Oslo , 7. In t in Oslo . Oslo daWe investigated the effects of exposure to traffic-related air pollution during pregnancy in selected urban and county areas of Norway on birth outcomes, including birth weight and the length of gestation.N = 22149). We excluded consequently participants with missing pregnancy NO2 exposure information (N = 3876), multiple births (N = 664) and non-live births (N = 76). Only data on singleton live births were used in the analysis. Total number of participants from the studied areas with non-missing air pollution exposure data was 17533 (born from 2001 to 2009), of which 4669 from Oslo, 7554 from Akershus, 3869 from Bergen and 1441 from Hordaland (Table th April 2011.The Norwegian Mother and Child Cohort Study (MoBa) is a prospective population-based pregnancy cohort study conducted by the Norwegian Institute of Public Health , 9. PartN = 718, 9.5 %), we used data from ultrasound measurements to determine gestational age. We also studied binary outcomes: low birth weight (<2500 g) and preterm delivery (<37 completed weeks of gestation).For assessing birth outcomes we used continuous MBRN variables birth weight (grams) and gestational age (weeks). Air pollution can potentially affect the size of developing foetus. Therefore estimating gestational age was based on the last menstrual periods as estimates based on ultrasound assessments are dependent on early foetal growth . If infoThe following characteristics were also extracted from the MBRN: sex of the child , parity , mother’s age at birth (years), marital status . Questionnaire information was used to determine: maternal education ), maternal smoking during pregnancy , maternal weight at the beginning of pregnancy (kg), maternal height (cm). Exposure to air pollution was estimated at the registered address at delivery. Women who did not change their address during pregnancy were used in a sensitivity analysis. Area variable was defined by the location of the address at delivery: Oslo, Akershus, Bergen, Hordaland.2 levels were built for the studied areas in order to account for regional specifics. In the models we used air pollution measurements conducted in 2010 for Oslo and Akershus, and in 2011 for Bergen and Hordaland. Measurement campaigns included three rounds of approximately two weeks duration with NO2 measurements  within a one year period. Measurement sites were selected to represent the range of residential exposure for each study area. For the analysis we included sites with no missing data, and no geocoding mismatches.Estimating air pollution exposure during pregnancy was based on the methodology developed for the ESCAPE project , 11. LUR2 level that was used for LUR modelling. LUR models were built separately for Oslo and Akershus. One model was built for Bergen and Hordaland together due to a low number of valid measurement sites for Hordaland. Predictors for building the LUR model were obtained from a GIS analysis of the N50 and VBASE maps (obtained in February 2013) providing information on land use, residential density, types of landscape and road network information. Predictor variables are listed in Additional file The mean exposures over the three measurement periods were averaged to obtain a yearly mean NO2 measurements were obtained from the Norwegian Institute for Air Research database “Luftkvalitet.info” for the period 2000–2012 in Oslo (used for Oslo and Akershus), and for the period 2003–2012 in Bergen . The daily estimates of exposure were calculated as the LUR-modelled yearly estimate multiplied by the ratio between daily NO2 routine monitoring station measurement and an annual average for the year when LUR measurement campaign took place. Daily NO2 exposure estimates were averaged separately for 1st, 2nd, and 3rd trimester, and also over the whole pregnancy. Exposures by trimester and the whole pregnancy exposure were highly correlated and therefore we decided to use one exposure estimate: the average NO2 exposure during the whole pregnancy.Yearly means of air pollution levels at residential address at birth were estimated using the resulting LUR models. Variables in models were truncated in accordance to the range of corresponding variables used for LUR model building. Negative modelled values were replaced with 0.01. In order to account for temporal variability, we used the ratio method of back-extrapolation to the period of each pregnancy using continuous routine monitoring station data . Daily N2 exposure and birth weight and gestational age. Logistic regression models were used to evaluate associations between pregnancy NO2 exposure and low birth weight and preterm delivery. The results are presented for both crude and adjusted models for a 10 μg/m3 increase in NO2. Adjustment variables were selected based on the literature analysis. Model 1 is adjusted for: maternal education, birth season, sex of child, maternal age, maternal marital status, maternal smoking during pregnancy, and maternal height. Model 2 contains Model 1 adjustment plus the area variable. Model 3 contains Model 1 adjustment plus parity and maternal weight. We performed stratified analysis by area , smoking status of the mother during pregnancy, parity, sex of child, maternal education level, and season of birth in order to explore potential effect modifiers. Sensitivity analysis of the results was performed in a subgroup of women who did not change address during pregnancy and in a subgroup of women for whom gestational age was determined from the last menstrual period – as a preferable method for assessment of potential effects of air pollution on the size of the developing foetus [We used linear regression models to analyse associations between pregnancy NOOverall birth weight was lower in cities (Oslo and Bergen) and higher in the two county areas , however, these differences were less prominent when comparing birth weight within each parity strata Table . Having 2 yearly means are presented in Table 2 model were area of water in the buffer of 500 m, distance to major road, and agricultural areas within the buffer of 1000 m. The model for levels of NO2 in Bergen and Hordaland included the following: lengths of major roads within the buffers 50 m, 50 to 100 m, 100 to 1000 m, inverse squared distance to port, high and low density residential land within the buffer of 1000 m, altitude, agricultural area within the buffer of 1000 m, and distance to the sea. The adjusted R2 of the models ranged from 59 to 87 % , and lowest in Hordaland county (6.3 μg/m3)  compared to those exposed to below 20 μg/m3 NO2, with estimated 60 g difference in means (p< 0.0001) between these groups   g per 10 μg/m3 NO2 (Table N = 15829) did not change substantially from the results in the main analyses.Comparing the overall birth weight distributions, we found a shift towards lower birth weight in children with pregnancy exposure to NOups Fig. . The sam47) Fig. . In the 2 and birth weight were seen only in children born in spring , Lee et al. 2003 (exposure between months 3 and 5) [Birth weight is associated with a variety of different factors: genetic and ethnic background, parity, maternal weight, socio-economic factors, medical conditions before or during pregnancy, and maternal lifestyle variables, most notably smoking during pregnancy . The rol3 and 5) , 14. How3 and 5) , 16 even2 and birthweight was attenuated and no longer statistically significant when adjusting for study area. Our area variable may reflect the spatial distribution of air pollution, representing by itself the proxy of exposure, or it may represent unmeasured factors in each study area which also influence birth weight and pregnancy length. The area means for modelled NO2 range from highest in Oslo to lowest in Hordaland (Table 2 levels on local scale. Areas may differ by mean levels of air pollution exposure, as well as by socioeconomic and lifestyle characteristics. For instance, social classes may be differently distributed within polluted areas depending on a region [In our study, the association between pregnancy exposure to NOnd Table , thus ada region . In the a region .Fig. 2SiAmong the potential area-specific factors that attenuate the association of birth weight with air pollution exposure, our study singled out the combination of parity and maternal weight. These factors may be related to lifestyle, socioeconomic situation, and health state of mothers, and can vary by study area. Specifically in Norway, families with more than one child tend to move out from large cities, which may explain the difference in distribution of parity by study area. Stronger associations of air pollution exposure with adverse birth outcomes have been reported in less economically advantaged classes , 20. In 2 exposure during pregnancy with gestational age and preterm delivery. This is in line with other studies also reporting no association of NO2 exposure with preterm delivery [Our study found no association of NOdelivery , 22.The important strengths of our study include standardized exposure assessment, detailed information on potential confounders, and a large study population. We highlighted the importance of area-specific factors that may confound the association between air pollution exposure and pregnancy outcomes. Our results suggest that these factors should be given a proper consideration in large multicenter studies. Further research is needed for identifying potential critical windows of exposure. In our data, exposures by trimester were highly correlated with whole pregnancy exposure. We assessed exposure at residence, but for more detailed individual exposure it is advisable to consider estimating exposures during travel and frequency of visits to city center. Most of our study participants did not move during pregnancy, but we did note a difference in distribution of multiparous women in our study areas, with higher proportion of them living in counties, and not in the cities. Besides the identification of the important confounders, such as parity and maternal weight, we might still have the residual confounding of unmeasured lifestyle factors in our data.2 during pregnancy was associated with a decrease in birth weight in some models. However, when adjusting for area-related and lifestyle factors this association was attenuated. We found no statistically significant associations of air pollution exposure with gestational age, low birth weight and preterm delivery.In this large pregnancy cohort with detailed information on lifestyle and pregnancy factors, land use regression modelled exposure to NO


Manganese (Mn) is an essential element for humans, but exposure to high levels has been associated with adverse developmental outcomes. Early epidemiological studies evaluating the effect of Mn on fetal growth are inconsistent.We investigated the association between maternal urinary Mn during pregnancy and the risk of low birth weight (LBW). Mn concentrations in maternal urine samples collected before delivery were measured in 816 subjects (204 LBW cases and 612 matched controls) recruited between 2012 and 2014 in Hubei Province, China.The median Mn concentration in maternal urine was 0.69 μg/g creatinine. Compared to the medium tertile of Mn levels, an increased risk of LBW was observed for the lowest tertile (≤0.30 μg/g creatinine) , and a significantly increased risk of LBW was observed for the highest tertile (≥1.16 μg/g creatinine) . A curvilinear relationship between maternal urinary Mn and risk of LBW was observed, showing that the concentration at 0.43 μg/g creatinine was the point of inflection. Similar associations were observed among the mothers with female infants and among the younger mothers < 28 years old. However, among the mothers with male infants or the older mothers ≥ 28 years old, only higher levels of Mn were positively associated with LBW.Lower or higher levels of maternal urinary Mn are associated with LBW, though only the association of LBW risk and higher levels of Mn was statistically significant. The findings also show that the associations may vary by maternal age and infant sex, but require confirmation in other populations.The online version of this article (doi:10.1186/s12889-016-2816-4) contains supplementary material, which is available to authorized users. Low birth weight (LBW), a birth weight less than 2,500 g, constitutes a significant public health problem in both developing and developed countries. The estimated 30 million LBW infants born annually  worldwide often face severe short- and long-term health consequences . LBW is Manganese (Mn) poses a particular challenge in that it is an essential nutrient for normal development, with involvement in bone formation, protein and energy metabolism, and metabolic regulation, but it is also a potential toxicant if overexposure occurs . Mn occuUnlike other toxic metals like lead, which have no beneficial use in the human body, the effects of Mn on fetal growth are likely to be more complex because it is both an essential nutrient and a potential toxicant, depending on the amount of exposure. Findings from studies evaluating prenatal exposure to Mn and birth size have been inconsistent. Maternal exposure to elevated levels of Mn in water has been associated with a reduction in birth weight . HoweverThese studies on Mn exposure and infant birth weight were limited to only include normal birth weight infants or included only a few LBW infants in their study populations and therefore couldn’t estimate the risk for LBW. With the high rate of industrial development and urban expansion in China, elevated levels of Mn in air and soil have been reported in some areas , 18, whiThe subjects in this study were participants in the prospective Healthy Baby Cohort (HBC) study. This study was conducted at three major maternity hospitals in Wuhan, Ezhou, and Macheng cities, which are located in Hubei province, in the central of People’s Republic of China. Between November 2012 and April 2014, 16,293 women who gave birth at any of the three hospitals were recruited, and the participation rate was 78.7 %. Participant mothers received a detailed explanation of the study procedures and provided written informed consent at enrollment. The research protocol was approved by the ethical committee of Tongji Medical College, Huazhong University of Science and Technology, and the three study hospitals.In this study, cases were mothers who delivered a singleton live infant with a birth weight < 2,500 g. Controls were mothers who delivered a singleton live infant with normal birth weight between ≥ 2,500 g and < 4,000 g. Potential cases and controls were excluded if they gave birth to multiple infants, a stillborn infant, or an infant with a birth defect. Women who did not have urine samples available for analysis were also excluded. For each case selected, three consecutive individual controls were randomly selected and matched to one case by delivery hospital, infant sex, and maternal age at conception . If more suitable matched controls were available for one case, only the top three with the closest maternal age to the case were selected. A total of 204 cases and 612 matched controls were included in the analysis.Women were interviewed after delivery by specially trained nurses in the three hospitals. The questionnaire collected information regarding demographic factors, household income, education, smoking behavior, and alcohol consumption. Information on birth outcomes, reproductive history, disease, and pregnancy complications were abstracted from the medical records. The pre-pregnancy body mass index (BMI) of mothers was calculated using the self-reported weight before pregnancy and height, which was measured using a stadiometer. Gestational age was calculated by subtracting the date for the last menstrual period from the date of delivery. Infant birth weight was measured by delivery room staff using standardized anthropometric procedures.3 was added to the final volume of 5 mL for overnight nitrification. The resulting sample was digested by ultrasound at 40 °C for 1 h and then analyzed using inductively coupled plasma mass spectrometry . The standard Reference Material Human Urine  was used as an external quality control, and sample spike-recoveries were used to confirm analytical recovery, which was 95 %. A 3 % HNO3 blank was processed in each batch of samples to control for possible contamination. The samples were analyzed with an external calibration method, using eight standard concentrations ranging from 0 to 500 μg/L. The limit of detection (LOD) for Mn in urine was 0.05 μg/L. Field blanks were also included for quality control and the levels of Mn in the field blanks were < LOD. The urine samples below the LOD were given a value one-half the LOD. Lead, arsenic, cadmium, and thallium were also measured simultaneously because previous studies have suggested that these metals are potentially associated with decreasing birth weight . For mothers that gave birth to female infants, lower and higher Mn levels were associated with increased risk of LBW compared to the medium tertile , although the associations were not significant. For mothers that gave birth to male infants, a positive association with LBW was only observed for the highest tertile of Mn [adjusted OR = 1.88 ]. Also, there was no statistical evidence of heterogeneity in risk according to infant sex (P heterogeneity = 0.24). Moreover, we obtained consistent results with the restricted spline models, showing that a non-linear risk pattern in younger mothers and mothers who gave birth to female infants . For older mothers and mothers who gave birth to male infants, we observed a possible linear trend between maternal urinary Mn concentrations and risk of LBW .Results for stratified analyses by maternal age (<28 and ≥ 28 years) and infant sex are shown in Table a priori hypothesis, and supports the idea that Mn may contribute to adverse birth outcomes at both low and high exposure levels.In this nested case–control study, we observed an increased risk of LBW for maternal urinary Mn levels in the lowest tertile and highest tertile, though the associations with LBW risk were only significant for higher levels of urinary Mn. These associations were observed even after adjustment for known and suspected risk factors for LBW. We further identified a curvilinear relationship between maternal urinary Mn level and risk of LBW, which was apparent in female infants. The observed relationship was consistent with our The number of studies on biomarkers of Mn has been increased during recent two decades, but the results on the representative biomarkers of Mn are contradictory, including Mn in urine, blood and hair. Some studies showed that urinary Mn may have limited use for occupational population as a direct measure of Mn exposure due to high variability within person over time , 31. HowIn the present study, none of our study participants had a urinary Mn level higher than the upper limit of normal urinary Mn values for adults 10 μg/L) . Table 5 μg/L . TCurrently, there are no recommended values or guidelines for ideal urinary or blood Mn levels during pregnancy. In this study, we used the medium tertile of urinary Mn as the reference group, and observed that both the lowest and highest tertile were positively associated with LBW. One explanation for the weaker association between the lowest tertile of Mn and LBW risk might be that the prevalence of Mn deficiency is low in our population. In a previous study, Eum et al.  assessedn = 125). Interestingly, in consistent with the studies, we also found a potential U-shaped relationship between maternal urinary Mn level and risk of LBW. However, the non-linear relationship may vary by maternal age and infant sex, and the non-linear pattern was apparent in mothers who gave birth to female infants.Some previous studies also investigated the relationship between maternal Mn exposure and infant birth weight. Vigeh et al.  reportedInfant sex is known to influence pregnancy outcomes, and female infants are usually at higher risk of LBW since male infants have consistently higher birth weight throughout gestation compared to female infants . HoweverWith respect to maternal exposure to higher levels of Mn being associated with LBW, one biologically plausible mechanism could be oxidative stress caused by high levels of Mn, leading to impairment of cellular function and growth . ExperimOne of the strengths of our study is that the nested case–control design provided the opportunity to include all of the LBW infants in the cohort, and the cases and controls were matched on potentially important factors in order to reduce the influence of confounding. The other strength of our study includes the availability of interview data and medical records from all participants, which allowed us to adjust for other potential risk factors for LBW.The limitation of this study is that Mn levels were measured in maternal urine at one spot time, which may not accurately reflect maternal Mn load or fetal exposure during the entire pregnancy. Biliary excretion is the main pathway by which Mn is excreted with most of the element ultimately being excreted in the feces , and uriOur nested case–control study found that both lower and higher levels of Mn concentration, as measured in maternal urine before delivery, was associated with increased risk of infant LBW. The associations were further observed to vary by maternal age and infant sex. This observation suggests that Mn levels during pregnancy may be important for fetal growth.


Type 2 diabetes (T2DM) is increasing in prevalence in Indigenous Australian children and adolescents. High rates of diabetes in pregnancy (DIP) in Indigenous Australians increases the risk of diabetes for the next generation. DIP is associated with neonatal adiposity, which correlates with long-term risk of obesity and diabetes. Indigenous Australians have high rates of low birth weight and increasingly, large for gestational age associated with DIP.The aims are: 1. To evaluate adiposity in babies born to Indigenous mothers and those of European background with DIP in the Northern Territory; 2. To evaluate the relationship between maternal factors and neonatal birth weight and body composition.Thus far 266 mothers and neonates from the PANDORA cohort  have been assessed. Neonatal anthropometrics were performed on all neonates, including skin fold measures. Calculations of fat mass were made using a validated equation (fat mass=0.39055(birth weight)+0.0453(flank skinfold)-0.03237(length)+0.54657).Significant differences were found in maternal characteristics between Indigenous and European background participants, including diabetes type , smoking in pregnancy  and location of residence . Gestational age at birth was significantly different (38.2 vs 39 weeks p<0.001), however birth weight was not significantly different (3380 vs 3428g). Indigenous neonates had greater subscapular  triceps  and flank skin folds . This difference remained significant for the flank skin fold only, after adjustment for diabetes type and maternal body mass index (BMI). There was no significant difference in calculated fat mass. On regression analysis, maternal BMI, smoking, nulliparity and T2DM were each independently associated with birth-weight z-score.Recruitment to PANDORA is ongoing. Preliminary data reveals higher skin fold measures, indicative of adiposity, in Indigenous neonates. There was no significant difference in fat mass. Smoking, BMI, nulliparity and T2DM were independently associated with birth-weight z-score, ethnicity was not independently associated.