Experimental evidence indicates that fetal exposure to xenobiotics with the potential to interfere with the endogenous steroid hormone regulation of fetal development may reduce birth weight. However, epidemiological studies are limited. The aim of the study was to investigate whether potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight.n = 582) were compared to births by women referred to an OHC on the suspicion of other exposures than EDC (n = 620), and to a sample of births by all occupationally active women in the same geographical regions , including 1,077 births of the referred women’s non-referred pregnancies.Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected of being exposed to occupational reproductive hazards were included in the study. A job exposure matrix enabled estimation of potential occupational exposure to EDC on the basis of job title. Births by women potentially exposed to EDC (No indications of reduced birth weight or increased risk of preterm birth were found among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight compared to the sample of occupationally active women but not compared to other women referred to an OHC.Potential maternal exposure to EDC at Danish workplaces is not related to low birth weight or preterm birth among women referred to occupational counselling. Occupational exposures might be too weak on the average to cause these adverse effects or counselling at the OHCs is effective in preventing them. Endocrine disrupting chemicals (EDC) are exogenous substances that cause adverse health effects through interference with the endocrine system , 2. EDC Denmark has had regulation on worker protection since 1873. According to the Danish Working Environment Act, the employer is responsible for ensuring a safe and sound working environment (Executive Order no. 1072 of 7 Sept. 2010). If a potentially harmful reproductive risk is present at the workplace, including exposure to EDC, pregnant women may be referred to an Occupational Health Clinic (OHC) by their general practitioner or midwife for reproductive risk assessment. This usually happens between 8 and 12 weeks of gestation. The clinics perform a risk assessment based upon available evidence in order to assess if the pregnant woman may continue in her job or whether there is a case for intervention in terms of actions to reduce or eliminate hazardous exposures, restructuring of job tasks, reassignment of job functions or – as the ultimate and least desirable solution - maternity leave due to reproductive risks that could not be resolved otherwise , 14. RefAssuming that pregnant women referred to an OHC have a more hazardous occupational setting compared to pregnant women in general, since they are referred on the basis of a concrete suspicion of a harmful risk factor, these women constitute a relevant population to investigate. The national and complete coverage of the Danish Birth Register enable comparison of birth weight and gestational age of births by women referred to these clinics to all births in the same geographical regions. The aim of the present study was to examine if potential occupational exposure to EDC during pregnancy is related to preterm birth and/or low birth weight.The study population consists of pregnant women referred to an OHC for occupational counselling in two Danish regions (Copenhagen and Aarhus) in the 26 year period from 1984 to 2010. A sample of all occupationally active women giving birth in the same time period and the same geographical regions, constitute an external reference group. We made restrictions as to those who were working at the onset of their pregnancy, mother’s age at delivery 16–45 years, birth weight 1,000–7,000 g and gestational age 154–310 days. Furthermore, one birth was chosen by random sampling among women with two or more deliveries in each of the groups, which left 1,202 women referred to an OHC , and 346,544 in the external reference group including 1,077 births of the referred women’s non-referred pregnancies.Among women receiving occupational counselling, 582 were referred on the basis of suspected exposure to EDC (defined below) and 620 were referred due to other exposures. These 620 pregnancies constitute an internal reference group.Statistics Denmark [the Medical Birth Registry [Information about the study population obtained from the OHCs was linked to data from  Denmark  and the Registry . These lunlikely, possible or probable [Exposure status of referred women was determined by using a job-exposure matrix (JEM) developed by van Tongeren et al. . The JEMprobable .. The seven substance categories in the JEM were combined into one overall group of EDC.Women referred to an OHC have been assigned a Danish occupational code. The code for each woman was translated into one of the job titles in the JEM. All women possibly or probably exposed to EDC in their occupation, according to the JEM, were combined into one group labelled potentially exposedEvery person with permanent residence in Denmark is given a unique 10-digit Personal Identification Number (PIN) . In the We examined the following outcomes: gestational age and birth weight, birth weight at week 40, preterm birth (<37 weeks) and low birth weight (<2500 g). The limits of preterm birth and low birth weight were set according to the WHO definition .Group 1 (D1-2) refers to top leaders, managers and employees with skills at the highest level. Employees with skills at medium level are classified into group 2 (D3). Group 3 (D4-8) contains employees with skills at basic level, and group 4 (D9-0) contains employees with unspecified working skills. Since the DISCO-88 codes were first registered in our data from 1991, only mothers giving birth hereafter are included in this variable.To classify the mothers into four groups of SES, DISCO-88 codes were used . DISCO-816–24, 25–34 and 35–45 years), year of birth , parity , SES , ethnicity (Danish/non-Danish) and smoking at any time during pregnancy (yes/no).We performed linear regression analyses of the effects of potential exposure to EDC (yes/no) on gestational age (days) and birth weight (grams) respectively while adjusting for a fixed set of potential confounding variables defined a priori: maternal age (In addition to linear regression of continuous outcomes we computed odds ratios (OR) for preterm birth and low birth weight according to exposure status by logistic regression analyses. We adjusted for maternal age, year of birth, parity, SES, ethnicity and smoking habits during pregnancy.All calculations were made by the statistical program SAS version 9.3 .Table Gestational age was approximately equal across the three groups Table  and lineth week of pregnancy was marginally lower in the group potentially exposed to EDC compared to the external references. However, the confidence intervals overlap, indicating no significant difference in mean birth weight , but not when compared to internal referents .The proportion of preterm births among the women potentially exposed to EDC was marginally larger than the proportion of preterm births among the women in the internal reference group Table , but theThere was no difference in the proportion of children with low birth weight born to the women potentially exposed to EDC compared to the internal references Table . CompareA sensitivity analysis only including first births did not show any differences of importance for gestational age and birth weight between the three exposure groups (data not shown).In this prospective follow-up study of pregnant women referred to an OHC for counselling, we found no indications of reduced birth weight or increased risk of preterm birth among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight when compared to the external references. This might reflect an anabolic effect of EDC (for instance an estrogenic effect), but without consistent findings in analyses using the internal references, we consider this a chance or spurious result.Women referred to an OHC are presumed to represent a high risk group, and constitute thereby a preferable basis for investigation compared to a population based study. The present study design enables comparison between women referred to an OHC potentially exposed to EDC and women referred to an OHC but unexposed to EDC. These two groups are highly comparable, since they are expected to be similar in most aspects except exposure status. Furthermore, use of register data provides a large study population contributing to enhanced statistical power.These reassuring results can be understood in several ways. First of all, Denmark has a long tradition of worker protection regulation and the Danish Working Environment Authorities regularly performs inspections at Danish workplaces. Thus, potentially harmful chemical exposures of pregnant women at Danish workplaces are in general considered well controlled and chemically induced birth defects are rarely notified to the National Board of Industrial Injuries . TherefoOne limitation of this study concerns the determination of exposure to EDC. The risk of EDC might go undetected in the present study due to misclassification associated with determination of exposure status. Using a JEM does not necessarily give an accurate picture of exposure since exposure might vary within job titles .The JEM of van Tongeren et al. divides the chemical substances into seven substance categories . In the Finally and importantly, EDC are also found in many consumer products and the exposure besides the occupationally induced might be profound which would diminish the association in the present study. We know very little about what factors pregnant women are exposed to at home .Pregnant women with potential occupational exposure to EDC were not at increased risk of delivering preterm or low birth weight babies. Findings may reflect that exposure levels are low without impact on the studied reproductive outcomes or that occupational counseling result in effective preventive actions.


The present study identified that Myanmar mothers were highly exposed to cadmium. Prenatal maternal cadmium exposure was associated with an occurrence of low birth weight.Arsenic, cadmium and lead are well-known environmental contaminants, and their toxicity at low concentration is the target of scientific concern. In this study, we aimed to identify the potential effects of prenatal heavy metal exposure on the birth outcomes among the Myanmar population. This study is part of a birth-cohort study conducted with 419 pregnant women in the Ayeyarwady Division, Myanmar. Face-to-face interviews were performed using a questionnaire, and maternal spot urine samples were collected at the third trimester. Birth outcomes were evaluated at delivery during the follow up. The median values of adjusted urinary arsenic, cadmium, selenium and lead concentration were 74.2, 0.9, 22.6 and 1.8 μg/g creatinine, respectively. Multivariable logistic regression revealed that prenatal cadmium exposure (adjusted odds ratio (OR) = 1.10; 95% confidence interval (CI): 1.01–1.21;  Pregnant women and their fetuses are more vulnerable to adverse effects from the exposure of environmental toxic substances ,2,3. MeaThe toxicological effects of heavy metals could alter the physiological changes during pregnancy, the critical phase of fetal cell division and differentiation ,9. As anThe associations between prenatal exposure to environmental heavy metals and adverse birth outcomes have been evaluated to varying degrees over the last decades. In many studies, prenatal arsenic, cadmium and lead exposure were inversely associated with anthropological parameters of newborns, such as birth weight, birth length, and head circumference ,15,16,17Adverse birth outcomes such as a low birth weight and preterm delivery are closely associated with various lifelong mortality and morbidity risks ,23. GeneIn Myanmar, southern and central regions were confirmed to be highly contaminated with arsenic in the ground water ,28,29,30Environmental heavy metal exposure is an emerging public health issue in Myanmar. Previously, arsenic contamination has been confirmed in Myanmar ,29. WithThis study is part of a birth-cohort study conducted in Kyaunggone and Kyonpyaw townships of the Ayeyarwady region in 2016. These townships have been confirmed for high levels of arsenic contamination in ground water . A totalUrinary arsenic, cadmium, lead and selenium concentration were measured using octapole collision/reaction cell inductively coupled-plasma mass spectrometry . Original urine samples were 20-fold diluted with 1% nitric acid  and 2% 1-butanol  and filtered through a 0.45 μm pore membrane  connected to a disposable plastic syringe. Inductively coupled plasma (ICP) multi-element standard solution  was prepared by a gravimetric method. The detection limit (DL) was calculated as 3 times the standard deviation (SD) of procedural blanks. The average DL values for arsenic, cadmium, lead and selenium were 0.239, 0.025, 0.843 and 0.362 μg/L, respectively. The values under the DL were assumed as a half value of the DL. Analytical quality was assured by the repeated analysis of the samples against National Institute for Environmental Studies (NIES) Certified Reference Material No. 18 Human Urine  and Seronorm Trace Elements Urine . The certified values of Seronorm Trace Elements Urine for arsenic, cadmium, selenium and lead are 142 μg/L (acceptable range: 130–154 μg/L), 4.6 μg/L (acceptable range: 3.8–5.4 μg/L), 58.6 μg/L (acceptable range: 52.4–64.8 μg/L), and 40.3 μg/L (acceptable range: 35.1–45.6 μg/L), respectively. NIES No.18 Human Urine certified only for limited elements and this study could apply the certified values of arsenic (137 ± 11 μg/L) and selenium (59 ± 5 μg/L). The measured values of the reference materials were within the acceptable ranges. Urinary heavy metal concentration was then adjusted for creatinine. The urinary creatinine concentration was measured by an in vitro colorimetric Jaffe method using a commercial kit .The pretested questionnaire covered variables including sociodemographic characteristics, anthropological measures, smoking status, pregnancy and obstetric history. Delivery records included information regarding birth, such as the birth weight, the baby’s sex, the mode of delivery, the gestational age and other biological attributes of both the mothers and newborns. Smoking status was categorized as “no exposure at all” or “have or ever been or passively exposed”. In this study, a normal pregnancy outcome is defined as a term delivery without any complication. A low birth weight refers to a birth weight of less than 2500 g at term , and prep-value of less than 0.05.Data analysis was performed using Stata 13 . The urinary heavy metal concentration was converted to μg/g creatinine after adjusting for creatinine concentration over the entire analysis. A descriptive analysis was conducted to present means, medians, the interquartile range (IQR), the SD and percentage. A Wilcoxon rank-sum test was applied to compare the exposure levels among different birth outcomes. Multiple logistic regression models were used to identify the associations between prenatal heavy metal exposure and adverse birth outcomes. In the models, the dependent variable was either low birth weight (0 or 1) or preterm delivery (0 or 1). The independent variables included the creatinine-adjusted heavy metal concentration as continuous variables. Potential confounders were also included in the models on the basis of rational associations in previous studies ,13,19,35This study was approved by the Research Ethics Committee of the Graduate School of Medicine, the University of Tokyo (No. 11186) and the Department of Medical Research, Myanmar (ERC No. 009316). A material transfer agreement was obtained through the University of Medicine 1, Yangon, Myanmar. All the participants were voluntary, and informed consents were obtained after the explanation of the purposes of the study.A total of 493 participants were enrolled during the first visit. Of these, only 419 participants had complete information of delivery and urine samples for analysis in this study . The bacp = 0.020). It was also significantly different between normal deliveries and both preterm and low-birth-weight deliveries (p = 0.014). There was no significant difference from other heavy metal exposure levels.p = 0.017). The association was found to be consistent  even after adjusting with maternal age, maternal education, the baby’s sex, smoking status, the gestational age, being primigravida and antenatal visits in multivariate logistic regression. The gestational age  and being primigravida  were also found to be strong predictors of a low birth weight. There was no significant association between the maternal heavy metal concentration and preterm delivery, as shown in This study evaluated the effect of prenatal heavy metal exposure on adverse birth outcomes among the Myanmar population. Overall, the maternal urinary cadmium concentration was statistically different between normal deliveries, low-birth-weight deliveries and deliveries with both preterm and low birth weight. After adjusting for the confounders, this study revealed that a higher maternal urinary cadmium concentration increased the likelihood of a low birth weight but not preterm delivery.This study firstly examined the maternal urinary heavy metal concentration. The median value of maternal urinary arsenic, cadmium, selenium and lead concentration values were 74.22, 0.86, 22.51, and 1.75 μg/g creatinine, respectively. In comparison with the previous reports, the urinary arsenic concentration among the Myanmar population was much lower than those in the Argentinian population (median = 230 μg/L), the Bangladesh population mean = 336.7 μg/L), the Nepalese population (mean = 196 μg/g creatinine) and the Indian population (mean = 290 μg/L) .7 μg/L, ,38,39. IThis study is the first to report a comparatively higher concentration of cadmium among the Myanmar population. Despite smoking being a major source of cadmium exposure, there was no significant association between the smoking status and urinary cadmium concentration in this study. Therefore, it is suggested that the main source of cadmium exposure in Myanmar is diet, either water or food. In the previous study comparing the cadmium content in different food items, the GM for cadmium in rice (50 ng/g) was significantly higher than that of wheat-derived food such as bread (16 ng/g), flour (19.3 ng/g) and noodles (4 ng/g) . Other sSeveral studies have discussed the effect of heavy metal exposure on anthropometric measures of newborns ,16,47,48A low birth weight is considered as a significant public health concern as it has been highly associated with neonatal mortality and disease risk in adulthood . This stThis study also attempted to identify the associations between prenatal heavy metal exposure and preterm delivery. However, in this study, prenatal heavy metal exposure was not significantly associated with preterm delivery. This finding is consistent with the previous report, which stated that the arsenic concentration in drinking water was not significantly associated with an increased risk of preterm delivery in Taiwan . In the This study drew on many important strengths. The study was a birth-cohort prospective design including broad information on potential confounders. The study was conducted at three public general hospitals of the study area to minimize selection bias. The concentration of heavy metals was measured using a sensitive, robust and well-validated method (ICP-MS) and assured with certified reference materials. Multiple important heavy metals were adjusted for rather than the focus being on the exposure of only one heavy metal. This is the first study to report the effect of prenatal heavy metal exposure on birth outcomes among the Myanmar population. Some limitations of this study should also be considered. The present study failed to control the prenatal exposure of other toxic chemicals that may collectively affect birth outcomes. The nutritional intake was not fully considered in this study, although it is an important predictor of a low birth weight . The infThe present study provides baseline information concerning environmental heavy metal exposure among the Myanmar population. This study also indicates that Myanmar mothers were comparatively highly exposed to cadmium, which should be counted as a public health threat. Prenatal exposure to cadmium was positively associated with the likelihood of a low birth weight in Myanmar. Along with the previous evidence, these results suggest a follow up on whether the effect of early-life exposure on birth weight could increase the health risks in later life. This study clearly highlights the need to consider other health risks of cadmium exposure beyond birth outcomes among the Myanmar population.


Increased contraceptive use has been associated with a decrease in high parity births, births that occur close together in time, and births to very young or to older women. These types of births are also associated with high risk of under-five mortality. Previous studies have looked at the change in the level of contraception use and the average change in these types of high-risk births. We aim to predict the distribution of births in a specific country when there is a change in the level and method of modern contraception.We used data from full birth histories and modern contraceptive use from 207 nationally representative Demographic and Health Surveys covering 71 countries to describe the distribution of births in each survey based on birth order, preceding birth space, and mother’s age at birth. We estimated the ecologic associations between the prevalence and method-mix of modern contraceptives and the proportion of births in each category. Hierarchical modelling was applied to these aggregated cross sectional proportions, so that random effects were estimated for countries with multiple surveys. We use these results to predict the change in type of births associated with scaling up modern contraception in three different scenarios.We observed marked differences between regions, in the absolute rates of contraception, the types of contraceptives in use, and in the distribution of type of birth. Contraceptive method-mix was a significant determinant of proportion of high-risk births, especially for birth spacing, but also for mother’s age and parity. Increased use of modern contraceptives is especially predictive of reduced parity and more births with longer preceding space. However, increased contraception alone is not associated with fewer births to women younger than 18 years or a decrease in short-spaced births.Both the level and the type of contraception are important factors in determining the effects of family planning on changes in distribution of high-risk births. The best predictions for how birth risk changes with increased modern contraception and for different contraception methods allow for more nuanced predictions specific to each country and can aid better planning for the scaling up of modern contraception.The online version of this article (10.1186/s12889-017-4741-6) contains supplementary material, which is available to authorized users. The Lives Saved Tool (LiST) was designed to estimate the impact of a small set of interventions on child mortality. Over time the scope has increased to include a broader range of interventions and outputs . For the last 5 years, LiST has also sought to accurately capture the effect of family planning on child survival . The LivFamily planning may also influence mortality through redistribution of births to types with lower risk of child mortality. There is an extensive literature that links births under different conditions to increased mortality risk . These “Family planning could potentially reduce mortality among children under-five by reducing the proportion of births in these high-risk categories. For example, women might use contraception to delay pregnancy, resulting in more time between pregnancies. Stover and Ross  recentlyAn interesting finding from this analysis  was the The user of FamPlan can develop models using various options, setting goals for contraception, reducing unmet need, and by changing contraceptive method-mix. Based on these inputs FamPlan re-estimates births and the distribution of births into risk categories defined by mothers’ age, parity and birth spacing. These values are then passed to the Lived Saved Tool, where categories of risk are linked to sub-optimal birth outcomes  and from there to increased risk of neonatal mortality and later stunting and then to mortality risk. This work builds on the work of Stover and Ross  and furtWe used data from Demographic and Health Surveys (DHS) carried out in low- and middle-income countries to inform the type of birth we expect on average with changing mCPR and total fertility rate (TFR). We examined all publicly available surveys from DHS phase II and later, including 207 surveys covering 71 countries. These surveys represent an extensive library available to the public for research purposes starting in the early 1980s, including information about the timing and circumstances of recent births as well as current contraceptive practices among women of child-bearing age .% permanent, the percent of women using permanent methods of contraception  among those that use modern contraception and % long acting and reversible, the percent of contracepting women who used IUDs or implants. We described the risk category for each birth in the 3 years prior to each survey. Assessment of risk was based on three characteristics: birth spacing, mother’s age at birth, and parity. We divided birth spacing into four categories based on mortality risk: preceding birth space less than 18 months, preceding space 18 to 24 months, preceding space 24 to 36 months, and preceding space 36 months or longer. We described mother’s age in three categories: less than 18 years, 18 to 34 years, and 35 or more years. For parity, we categorized births as first births, second to fourth births, or fifth and later births. We predicted average changes in birth risk across surveys with three different models with increasing complexity. In the first model we predicted changes in birth risk with changing mCPR using a log linear regression for each risk category. For the second model we estimated these relationships between mCPR and percent of births in each category using log linear regression while adjusting for method-mix. For the third model, we modelled associations between the national percent of births in each risk category and rates of mCPR using multilevel log linear regression with random effects for country of survey. We transformed the percent in each risk category with the natural logarithm as the independent response. For each birth risk category, and the expected percent of births in that category pi in country i, the relationships between percent at risk (pi), mCPR, and method-mix are modelled in this framework bybi is specific to each country, and regression coefficients β0, β1, β2, and β3 are associations common to all countries. In each dimension of risk , several pi are modelled for each category. The resulting predicted percentages are scaled to cover 100% of births.Method-mix in each survey was specified by pi used empirical Bayesian methods for multilevel data to further refine predictions of birth risk distribution with the random effect bi [This model for each fect bi . Althougfect bi , althougfect bi , 20 and fect bi . A hierafect bi  and McCufect bi . These pfect bi , while iWe also examined the relationship between birth risk distribution and mCPR in order to demonstrate the relative advantage of country-specific methods. We estimated the average linear association across survey data, and compared with results from hierarchical modeling with country-specific effects. We examined the predicted birth risk distribution for a selection of low- and middle-income countries. We also predicted the percent of births in each of the categories described above in these countries for three scenarios: (A) increasing mCPR with permanent methods, (B) increasing mCPR with long acting and reversible methods, and (C) increasing mCPR with short-term methods, that is, modern methods that are not permanent or long acting such as condoms, injections, and pills. We examine these scenarios for an increase in mCPR of 10% from the most recent estimated mCPR.A summary of the average percent of births in each of these categories from the 3 years prior to survey is shown in Table The estimated associations between mCPR and percent at risk for three different models are shown in Table At the crudest level, model 1 indicates no statistically significant association between mCPR and short birth intervals (<18 months) and births to younger women aged less than 18 years. Association with other categories was statistically significant and in the expected direction. For example, fewer births to older women and births with high parity are associated with increased mCPR. However, for birth interval, increased mCPR is associated with reduced percent of births with the optimal preceding interval of 24–35 months. Only the proportion of births with preceding interval of 36 months or more is positively associated with prevalence of mCPR. These relationships change when method-mix is introduced (Model 2). Specifically, the association between short birth interval and prevalence of mCPR changed direction and became statistically significant. Model 3, which accounts for country specific random effects, showed similar results as models 1 and 2. All parameter estimates for the hierarchical model are included in Additional files Finally, as a way to visualize the impact of different contraceptive methods on the distribution of births into risk categories, we predicted the percent of births in each category described above for three scenarios: (A) increasing mCPR with permanent methods, (B) increasing mCPR with long acting and reversible methods, and (C) increasing mCPR with short-term methods. We made these predictions for Zambia and Nicaragua, starting from the most recently estimated mCPR , with predominantly methods that are not permanent or long term, scaling up by 10% among women age 15 to 49 years. Estimated distributions of birth space, birth order, and mother’s age are shown for Zambia in Fig. We have used recent mCPR and contraception method-mix from nationally representative household surveys to predict the distribution of high-risk births for unobserved ranges of mCPR. This analysis confirmed at a crude level, as in the earlier analyses reported by Stover and Ross , that thThis work builds on previous research on contraceptive method-mix , allowinThe analytical methods in this analysis examined a relationship between mCPR and proportion of high-risk births that is common across countries, while using hierarchical methods for a specific country to predict how birth risk will change with increased mCPR or with a change in the contraceptive method-mix. This method takes systematic advantage of national data to make predictions within each country. Stark differences were observed between the mCPR rates as well as the distribution of high-risk births for surveys from different regions in our analysis. Specifying the type of contraception being used allows more specific predictions for the percent of high-risk births, and random effects for surveys from the same country gives that country’s data more influence in their prediction than surveys from other countries.These country specific predictions including contraception method-mix can be incorporated into the framework of the Lives Saved Tool. Every country with a recent national survey including a full birth history has an estimated random effect for each birth risk category Additional file 2:Graphics for the predictions in the scenarios as shown for Zambia and Nicaragua for 71 countries are included. (PDF 111 kb)Additional file 3:Additional predictions for how birth spacing will change with mCPR ranging between 20 and 80% for similar scenarios are shown for 71 countries. (PDF 1962 kb)


Previous epidemiologic studies have considered the effects of individual air pollutants on birth outcomes, whereas a multiple-pollutant approach is more relevant to public health policy.2.5) and polycyclic aromatic hydrocarbons (PAH) (a component of PM2.5) exposures on birth outcome deficits, assessed by the single vs. two-pollutant approaches.The present study compared the observed effect sizes of prenatal fine particulate matter (PM2.5 and PAH were monitored in the second trimester of pregnancy. The exposure effect estimates (unstandardized and standardized regression coefficients) on birth outcomes were determined using multivariable linear regression models, accounting for relevant covariates.The study sample included 455 term infants born in Krakow to non-smoking mothers, among whom personal exposures to PM2.5, in terms of standardized coefficients. In the two-pollutant approach, the negative effect of PM2.5 on birth weight and length, adjusted for PAH exposure, lost its significance. The standardized effect of PAH on birth weight was 10-fold stronger  than that estimated for PM2.5 .In the single-pollutant approach, each pollutant was inversely associated with all birth outcomes. The effect size of prenatal PAH exposure on birth weight and length was twice that of PM2.5. Though in the single-pollutant models PM2.5 had a significant impact on birth outcomes, this effect appears to be mediated by PAH.The results provide evidence that PAH had a greater impact on several measures of fetal development, especially birth weight, than PMThe online version of this article (doi:10.1007/s00420-016-1192-9) contains supplementary material, which is available to authorized users. The number of epidemiologic studies on the adverse impact of air pollutants on population health has grown rapidly over the last decades; and they have provided strong evidence that both short and long-term exposures to airborne pollutants are associated with greater mortality and morbidity risks in adults and children  of PM  and ultrafine (PM0.1) mode , this creates problems in interpreting results for public health policy in causal terms.To date, few studies have used individual  estimation of fetal exposure to air pollutants; most have relied on proxy exposure data to certain pollutants, which were routinely monitored within a given residential area and often based only on one or two monitoring stations. Moreover, in many studies the main pollutant exposure was limited to PM, which irrespective of its size range, is in fact a multi-pollutant agent containing a varying mixture of chemicals. As TSP, PMUp to now, worldwide public health policies regarding air pollution hazards have generally been directed at controlling single pollutant exposures, although the polluted air we breathe is a complex mixture of pollutants in solid and gaseous states. The single-pollutant studies are relatively straightforward to conduct, and their results are easy to understand. However, this approach fails to consider the total population health responses resulting from the simultaneous exposure of two or more pollutants and does not account for the relationship between given pollutants in the context of specific health risks.2.5 and PAH) is the better predictor of birth outcomes and to test the hypothesis that prenatal PAH exposure is the main etiological agent responsible for adverse birth outcomes. In the present analysis, data from our prospective birth cohort study in Krakow (2000–2004) were analyzed , medical and reproductive history, occupational hazards, alcohol consumption, and smoking practices of others present in the home. After birth, maternal and child hospital records were reviewed to obtain data on complications of delivery. Weight, length, and head circumference (HC) at birth were recorded for all infants. Gestational age at birth was defined as the interval between the last day of the mother’s LMP and the date of birth. Finally we analyzed data of 455 children as preterm births (<37 weeks of gestation age) and outliers (PM2.5 and PAH concentrations above 95% of their distributions) were excluded from analysis.The prospective cohort study design and detailed selection of the population are previously described  measured particle mass. The PEMS is designed to achieve the particle target size of ≤2.5 μm at a flow rate of 4.0 L min with an array of 10 impactor nozzles. Flow rates were calibrated (with filters in place) before the monitoring and were checked again with the battery pack change on the second day and at the conclusion of the monitoring. Pumps operated continuously at 2 L/min over the 48 h period. To modify the sampler to achieve the 2.5-μm size cutoff at 2 L/min, five of the nozzles were blocked. Particles were collected on Teflon membrane filter . The combination of low pressure drop (permitting use of a low-power sampling pump), low hygroscopicity (minimizing bound water interference in mass measurements), and low trace element background  of these filters makes them highly appropriate for personal particle sampling. Dust air samples were analyzed by the Department of Environmental Health, School of Public Health, Harvard University (JD Spengler).a)pyrene, benz[a]anthracene, chrysene/is chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, indenopyrene, dibenzanthracene, and benzoperylene—as described , with recovery means ranging from 91 to 117% and recovery standard deviations from 18 to 31%. We did not adjust air concentrations for spike recoveries. Two laboratory technicians analyzed all PAH samples using the same technique. Measurement agreement of the duplicate PAH samples was >90% over the 2-year exposure assessment period. The detection limit for each target PAH was 1.0 ± 0.2 ng/sample; 100% of the air samples were above the detection limit for all PAH except for DA (73% >detection limit).The air extracts were analyzed at Southwest Research Institute (SWRI) by gas chromatography/mass spectrometry for pyrene and the eight carcinogenic PAH— benzo(n = 84), indoor air was monitored over six weeks during the third trimester concurrent with the personal air monitoring over 48 h The prenatal personal air concentrations were significantly correlated with indoor levels of PAH (sum of the 8 carcinogenic PAH)   was calculated as sum of all nine monitored PAH. Correlations between PAHtotal and monitored PAH compounds were between 0.94 and 0.99.For quality control (QC), each personal monitoring result was assessed for accuracy in flow rate, time, and completeness of documentation. Samples not meeting QC criteria for adequacy were not included in the analysis. We validated 48 h personal monitoring as an indicator of longer-term, integrated exposure in two ways. In a subset of NYC cohort study (2.5 and PAH concentrations above 95% of their distributions) were excluded from analysis. We constructed several models with exposures to PM2.5 or PAH treated as continuous. Crude effects were estimated and subsequently adjusted to confounders. All maternal factors included in multivariate analyses were related to birth outcomes in bivariate analysis. Next, we assessed the effects of PM2.5 and PAH exposure on each birth outcome by multiple linear regression, controlling for potential confounders . We tested season of birth for confounding because of its association with exposure and potential association with fetal growth. Season of birth was introduced in the regression models as a dummy variable, with summer defined as the reference level. Because the distribution of the air pollutants was skewed, the PM2.5 and PAH values were log transformed before entry into the regression models. To estimate the overall effect of PM2.5 and PAH each pollutant model was run in turn (single pollutant models) and then independent effect of each pollutant was modeled by including both PM2.5 and PAH in the same multivariable model (two-pollutant model). The interaction term between PM2.5 and PAH was statistically non-significant in all outcomes (p > 0.3), so it was not included in final models. As PM2.5 and PAH were significantly inter-correlated , we tested multicollinearity between log transformed measures using Variance Inflated Factors (VIF). VIFs were equal to 1.51, which is an acceptable level for inclusion in the same model  and outliers  measured in pregnant women during the second trimester varied between 27.3 μg/m3 in the non-heating season (May–September) and 43.4 μg/m3 in the heating season (October–April) . The median level of PAH measured in the heating season was sevenfold higher compared with that in the non-heating season.Personal PM2.5 were lower in the non-heating season  than in the heating season  . Figure 2.5 ratios calculated for each participant in the study across the seasons, and between individual participants within each season.Pairwise correlation coefficients between PAH and PM2.5 and PAH (ln-transformed) on birth outcomes, where the unstandardized coefficients and the standardized effect size of the exposure (Beta coefficients) were appraised. All potential confounders, except from environmental tobacco smoke, introduced in the models were statistically significant. Full models are available in supplemental materials (Tables S1-S3).Table 2.5 and PAH exposures were found individually to be inversely associated with birth weight. Newborns experienced a birth weight deficit of 78.8 g (unstandardized coefficients) with an increase of PM2.5 by one ln unit; the corresponding birth weight deficit in newborns exposed in the prenatal period to PAH amounted to 81.9 g by one ln unit. However, the standardized PAH effect size was twice that of PM2.5 (β = − 0.21 vs. β = − 0.10).Both PM2.5 showed a mean birth weight deficit of 12.7 g per increase of PM2.5 by one ln unit; the corresponding birth weight deficit attributed to PAH exposure in the prenatal period amounted to 77.0 g. The standardized and adjusted size effect of PAH in the two-pollutant model was highly significant and about ten times stronger  than that attributed to PM2.5 . The latter model results suggest that the negative effect of PM2.5 on birth weight in the single-pollutant model may have been mediated by the PAH component of PM2.5.In the two-pollutant model the newborns exposed to PM2.5 showed an average deficit in length of 0.5 cm for an increase of PM2.5 concentration by one ln unit; the corresponding deficit in birth length in infants exposed to PAH amounted to 0.5 cm. In terms of the standardized Beta coefficients, however, the deficit for PAH was about twice  that attributed to PM2.5 . In the two-pollutant regression model for prenatal exposure to PM2.5 and PAH on birth length, infants prenatally exposed to PM2.5 showed a mean deficit of 0.20 cm for an increase in the concentrations of PM2.5 by one ln unit; the corresponding deficit with PAH amounted to 0.39 cm. However, the Beta coefficient for PAH exposure in the two-pollutant model was roughly three times  that for PM2.5 . As in the two-pollutant approach for birth weight, the effect of PM2.5 on birth length appears to have been mediated by PAH.Both exposure variables in the single pollutant models were inversely and significantly associated with birth length. The newborns exposed prenatally to PMβ = −0.20, p = 0.004 for birth weight vs. β= −0.17, p = 0.025 for birth length).The adjusted PAH effect size on birth weight and length estimated in the two-pollutant model appeared to be approximately the same strength  and length and HC at birth  than in the heating period , suggesting large seasonal variation in the PM2.5 chemical composition and implying that fine particles in the heating season were more heavily loaded with PAH compounds compared with the non-heating period. The mean PAH-PM2.5 ratio was about five times higher in the heating season compared with the non-heating season. Irrespective of season, PM2.5 concentrations explained only 33.5% of variability of PAH. Our observations are consistent with PM chemical composition data, which varies greatly across regions and seasons, affecting toxicity  after adjustment for potential confounding factors and exclusion of preterm newborns and outliers. Importantly, the PAH effect size on birth weight and length was twice that of PM2.5 on birth weight, adjusted for PAH exposure, lost its significance, suggesting that the PAH component of PM2.5 fraction is more biologically relevant to birth outcomes than PM. Some residual confounding by PM2.5 could have resulted since fine particles measured in the study contained other compounds  not detected by the PAH measurement procedures but known to have potential negative health effects. The standardized effect size of PAH on birth weight established from the two-pollutant model was highly significant and about ten times larger  than that attributed to PM2.5 ; and the standardized effect of PAH on birth length was two times greater than that for PM2.5. In contrast, PAH did not appear to have a greater effect on HC than PM2.5.In the two-pollutant models, the negative effect of PM2.5 and PAH (z score transformed), while prenatal PM2.5 exposure was associated with birth outcomes in a linear manner, equally through lower and higher ranges of exposure, the relationship between PAH exposure and all birth outcomes was curvilinear, suggesting that both exposure factors may lead to detrimental effects on the fetal development through different biologic mechanisms.Comparing the patterns of associations between PM2.5 and PAH might cause adverse pregnancy outcomes are not well established. PM2.5 might be a proxy measure of a complex of toxic agents present in the environment, including PAH, that could adversely affect fetal growth. Fine particles are also virtually always present in combustion processes that generate other toxic agents. Typically, the ambient fine particle fraction contains organic compounds, sulfates, metals, and soot Supplementary material 2 (DOCX 81 KB)


Maternal metabolism during pregnancy is a major determinant of the intra-uterine environment and fetal outcomes. Herein, we characterize the maternal urinary metabolome throughout pregnancy to identify maternal metabolic signatures of fetal growth in two subcohorts and explain potential sources of variation in metabolic profiles based on lifestyle and clinical data.1H nuclear magnetic resonance (NMR) spectroscopy to characterize maternal urine samples collected in the INMA birth cohort at the first  and third trimesters of gestation (n = 417 and 469). Metabolic phenotypes that reflected longitudinal intra- and inter-individual variation were used to predict measures of fetal growth and birth weight.We used 1H NMR signals arising predominantly from steroid by-products. We identified 10 significant and reproducible metabolic associations in the third trimester with estimated fetal, birth, and placental weight in two independent subcohorts. These included branched-chain amino acids; isoleucine, valine, leucine, alanine and 3 hydroxyisobutyrate , which were associated with a significant fetal weight increase at week 34 of up to 2.4 % in Gipuzkoa (P < 0.005) and 1 % in Sabadell (P < 0.05). Other metabolites included pregnancy-related hormone by-products of estrogens and progesterone, and the methyl donor choline. We could explain a total of 48–53 % of the total variance in birth weight of which urine metabolites had an independent predictive power of 12 % adjusting for all other lifestyle/clinical factors. First trimester metabolic phenotypes could not predict reproducibly weight at later stages of development. Physical activity, as well as other modifiable lifestyle/clinical factors, such as coffee consumption, vitamin D intake, and smoking, were identified as potential sources of metabolic variation during pregnancy.A metabolic shift between the first and third trimesters of gestation was characterized by Significant reproducible maternal urinary metabolic signatures of fetal growth and birth weight are identified for the first time and linked to modifiable lifestyle factors. This novel approach to prenatal screening, combining multiple risk factors, present a great opportunity to personalize pregnancy management and reduce newborn disease risk in later life.The online version of this article (doi:10.1186/s12916-016-0706-3) contains supplementary material, which is available to authorized users. Fetal growth restriction (FGR) or excessive growth (macrosomia) affect 15 % and 10 % of all pregnancies, respectively . Beyond Exploratory metabolic profiling offers a powerful means of capturing systems-level information that reflects both maternal genetic and environmental influences, hence helping to elucidate metabolic disturbances and pathways associated with fetal outcomes –9. Our rTo our knowledge, the present study represents the largest human investigation  in which metabolic profiling of maternal samples has been used to understand the progression of normal fetal growth. This study aimed to (1) characterize the maternal urinary metabolome throughout pregnancy, (2) identify maternal metabolic signatures of fetal growth in two subcohorts, (3) explain potential sources of variation in metabolic profiles based on lifestyle and clinical data, and finally (4) to determine the individual importance of metabolic signatures versus other maternal factors on birth weight.INMA (INfancia y Medio Ambiente) is a birth cohort study in seven regions of Spain that aims to examine the role of environmental pollutants in relation to child growth and development. All participants were singleton live-born infants from two INMA subcohorts located in Gipuzkoa (Basque Country) and Sabadell  . The womFetal growth scores or standard deviation scores (z-scores) were obtained using longitudinal growth curves calculated for each individual adjusting for constitutional factors known to affect fetal growth . Unconditional z-scores at a certain time point describe the size of a fetus at this time and conditional z-scores describe the growth of a fetus during the respective time interval, i.e., at 12–20, 20–34, and 12–34 weeks of gestation . Anthrop1H NMR spectroscopy  were calculated. All multivariate statistical analyses were performed using MATLAB.Metabolic profiles, as digitized spectra, were subjected to exploratory analysis where multivariate projection methods such as principal component analysis (PCA) provided an overview of the data and helped identify the main sources of biological and technical variation and potential outliers. Differences between first and third trimester samples were further explored through the application of orthogonal-partial least squares discriminatory analysis (O-PLS-DA). In order to avoid over-fitting the data, a 7-fold cross-validation was used and statistical parameters  and modelled separately. Coefficients from the regression models were multiplied by the logarithm of 1.5 to derive an effect estimate for a 50 % increase in metabolite levels . RegressP value under 0.05 (P adjusted for by FDR using the function “P-adjust” in R). In addition, correlation adjusted scores (CAR scores) were used to measure the correlation between metabolite levels and all the Mahalanobis-decorrelated predictors in one model  as implemented in the R-package ‘care’ [We considered the following growth-related parameters: maternal clinical parameters, maternal lifestyle in third trimester, dietary intake in third trimester and sociodemographic characteristics of both parents, all of which have been previously reported to be strongly associated with birth weight .In order to estimate the importance of different pregnancy determinants of birth weight, including the third trimester urinary metabolite panel selected at step 2, we again used CAR scores. A selection of baseline characteristics of the study participants are presented in Table 2X = 13.5 %, PC2: R2X = 5 %, in Gipuzkoa, PC1: R2X = 5.8 %, PC2: R2X = 3.9 %). Discriminatory metabolites were identified from the O-PLS-DA coefficients . Steroid hormone by-products increased by 3-fold in the third trimester, including 5β-pregnane-3α,20α-diol-3α-glucuronide , a progesterone metabolite , and a mixture of estrogen metabolites which had previously been uncharacterized in 1H NMR spectra of maternal urine. The identity of P3G was confirmed by chromatographic isolation of the target feature  after normalization for sample dilution, provided a clear separation of the two trimesters sampled during pregnancy Fig. , b. Thisnts Fig. , d on thP < 0.05) at 12–34, 20–34, and 34 weeks of gestation and birth weight  and 1 % in Sabadell (P < 0.05). Similarly, estrogens were consistently associated with greater fetal growth between 12–34 and 20–34 weeks and fetal weight at week 34 and at birth (P = 0.007 in Gipuzkoa and 3.10-5 in Sabadell). Progesterone by-products, were solely associated with anthropometric measures at birth in contrast to estrogens, with a 0.3–0.6 % associated increase in birth weight (P = 0.001–0.02). BCAAs, estrogens and, to a lesser extent, progesterone by-products were found to be consistently correlated to each other suggesting a common source of biological variation. Other metabolites involved in glucose metabolism, including alanine and choline, presented similar trends with fetal weight outcomes. 3-hydroxybutyrate/3-aminoisobutyrate were significantly associated in both subcohorts with increased placental weight (+0.9 %).Based on longitudinal fetal ultrasound measurements and birth weight, fetal growth was assessed . Of 64 urinary metabolites present during the third trimester, 10 were associated in both subcohorts with greater growth .Using first trimester metabolic profiles, only creatinine/creatine were associated in both subcohorts with fetal growth with a 1.2 % change in weight at 12 weeks . Variation in vitamin D (serum 25-hydroxyvitamin) and thyroid hormones (T3) were also related to levels of BCAAs, 3-HIB, alanine, and choline (only in Gipuzkoa). Sabadell first trimester metabolite levels associated with reduced fetal weight at weeks 12 and 20  were specifically explained by sociodemographic factors (up to 8 % of variance explained) and smoking exposures , lifestyle , active and passive smoking, dietary intake), sociodemographic and clinical markers . Represented as yellow branches on the circos plot, metabolite levels were inter-related with clinical markers  and lifestyle factors, in particular smoking  was 48 % and 53% in Sabadell and Gipuzkoa, respectively  increase in birth weight. Through analysis of rich data on lifestyle and clinical markers, we have demonstrated further understanding of the inter-relationships between fetal/birth weight and maternal urinary metabolites.1H NMR despite previously being identified as important urinary markers during pregnancy [A large proportion of the metabolites measured were affected by the time of gestation but steroid by-products of progesterone and estrogens were particularly increased between week 12 and 34 (ca. 3-fold). Surprisingly, our study was the first to confirm the identity of these metabolites via regnancy –20. Accoregnancy , 22, whiregnancy . This phregnancy . In addiregnancy , 25. de novo in humans. Their homeostasis is therefore maintained by degradation and dietary intake only. BCAAs are potentially particularly important during gestation as an energy source, or utilized for biosynthetic purposes. They can be oxidized to keto-acids, which are in turn decarboxylated to form acetyl-CoA and succinyl-CoA, which eventually enter the Krebs cycle (TCA cycle) and produce ATP. BCAA oxidation is particularly important in cases of fasting or even in patients with type 2 diabetes and obesity, where there is a switch from glucose to other substrates such as ketone bodies, glucogenic amino acids, and fatty acids for energy production [n = 10) compared to controls (n = 84) [BCAAs are essential nutrients that cannot be synthesizedoduction . Some stoduction , 28. Pre(n = 84) . Signifi(n = 84) . The imp(n = 84) , 28, 30.(n = 84) . We also(n = 84) –34, and Urinary metabolites of steroid hormones were positively associated with fetal growth in the late stages of pregnancy in our study, which corroborate previous findings . StartinN-acetylneuraminic acid. Creatinine is the breakdown product of creatine and creatine phosphate, which are amino acid derivatives involved with cellular energy production, principally in muscles. Creatinine excretion during pregnancy was shown to decrease, as also observed in this study, as well as levels in serum due to increased glomerular filtration rate [First trimester metabolic phenotypes could mainly predict fetal weight at weeks 12 and 20, but not at third trimester and birth and with little consistency across the two populations. In Sabadell, metabolites related to (1) mitochondrial processes such as energy production through the TCA cycle or lipid metabolism, including for succinate, citrate, and carnitine, or (2) to oxidative stress were negatively associated with fetal weight and growth but also correlated to sociodemographic status and smoking. Renal changes and inflammation may be at the origin of some of the markers of early fetal growth impairment observed such as excreted creatine/creatinine , 5-oxoproline, carnitine, and ion rate . Interesion rate . Previouion rate . Early eion rate , 42. TheOur study benefitted from the use of two independent subcohorts for validation, which gives a realistic representation of the population at large in comparison with matched case–control studies that aim to minimize population homogeneity. The use of longitudinal ultrasound measurements and individualized growth curves for measuring fetal growth enabled several potentially critical windows throughout pregnancy to be explored. We note some study limitations. We have concentrated on the application of untargeted NMR spectroscopic-based profiling. This approach is limited with respect to its analytical sensitivity and spectral overlap of metabolite resonances, which was apparent for the steroid hormones. However, we successfully integrated the NMR spectroscopic analysis with HPLC fractionation and UPLC-MS in order to annotate a number of steroid hormones. Our work could be complemented with LC-MS-based platforms to enhance overall coverage as well as quantification of targeted classes of metabolites. This study also relied on spot measurements of urine, which display greater intra-individual variability in comparison to 24-h urine collection or first morning voids. We have identified novel inter-relationships between fetal/birth weight, metabolites, and lifestyle/clinical factors, but the cross-sectional nature of these data do not allow further causal relationships to be inferred. Rather, these findings capture the metabolic signatures of a myriad of physiological , genetic, environmental, and other lifestyle characteristics associated with fetal growth, but not one individual lifestyle/clinical parameter could largely explain the variation of a single metabolite.Different statistical frameworks were used to define the first and third trimester differences, assumed to have a strong systematic effect on the maternal urine metabolome, and to define metabolite to clinical growth data relationships, which were assumed to be more subtle in a free living population. More specifically, multiple linear regression was chosen for step 2  because of the ease of interpretation of multiple linear regression and to enable adjustment for confounding factors, including sampling time and birth-related variables. In particular, it was important to be able to quantify the impact of metabolite levels on growth z-score.The first scan visit at 11–14 weeks is the most pertinent clinical screening for high-risk pregnancies that would benefit from personalized management. The addition of metabolic markers to clinical assessment could provide further information on the physiological status of the pregnant mothers, in particular in case of failure of placental function due to oxidative stress. Up to now, no single biomarker was found to be predictive and specific enough for abnormal fetal growth (FGR or macrosomia) for clinical use, including in this paper. Clinical assessment may benefit from a combination of markers, including Doppler ultrasonography  and algoThe present study represents the largest human investigation (n > 800) in which non-targeted proton NMR spectroscopy has been used to understand the changes in urinary metabolic phenotypes over the course of pregnancy in two independent Spanish populations. We identified, for the first time, 10 maternal urinary metabolites predictive of fetal growth using longitudinal data and birth weight, including BCAAs and steroid hormone by-products. We could explain a total of 48–53 % of the total variance in birth weight, of which urine metabolites had an independent predictive power of 12 % adjusting for all other lifestyle/clinical factors. These results highlight prenatal maternal modifiable factors, i.e., metabolic phenotypes that are associated with fetal development. The current study identified metabolic markers in the third trimester, and the metabolic pathways identified, in particular BCAAs, could be the subject of future investigations in humans. This novel approach to prenatal screening, combining multiple risk factors, presents a great opportunity to personalize pregnancy management and potentially reduce disease risk in the later life of the newborn.


White matter (WM) abnormalities associated with prematurity are one of the most important causes of neurological disability that involves spastic motor deficits in preterm newborns. This study aimed to evaluate regional microstructural changes in diffusion tensor imaging (DTI) associated with WM abnormalities.We prospectively studied extremely low birth weight  preterm infants who were admitted to the Neonatal Intensive Care Unit of Hanyang University Hospital between February 2011 and February 2014. WM abnormalities were assessed with conventional magnetic resonance (MR) imaging and DTI near term-equivalent age before discharge. Region-of-interests (ROIs) measurements were performed to examine the regional distribution of fractional anisotropy (FA) values.p = 0.022), the ipsilateral posterior limb of the internal capsule (p = 0.019), and the ipsilateral centrum semiovale (p = 0.012) compared to normal WM and WM abnormalities without CP. In infants having WM abnormalities with CP, early FA values in neonatal DTI revealed abnormalities of the WM regions prior to the manifestation of hemiparesis.Thirty-two out of 72 ELBW infants underwent conventional MR imaging and DTI at term-equivalent age. Ten of these infants developed WM abnormalities associated with prematurity. Five of ten of those with WM abnormalities developed cerebral palsy (CP). DTI in the WM abnormalities with CP showed a significant reduction of mean FA in the genu of the corpus callosum  contains supplementary material, which is available to authorized users. Despite the recent advances in both antenatal and neonatal intensive care, neurodevelopmental outcomes in those born prematurely have improved little over time. Many studies have reported that neurodevelopmental disorders observed in preterm infants comprise motor and cognitive impairment, language delays, behavioral disorders, and psychological problems –3.White matter (WM) abnormalities associated with prematurity are the predominant cause of neurological disabilities in preterm infants. Periventricular foci of necrosis in preterm infants are caused by multifactorial insults including hypoxia-ischemia, infection/inflammation and coagulation disturbance at a particular timing of brain development . Early pThe diffusion tensor imaging (DTI) of advanced MRI reflects changes in WM connection and myelination by the detection of water anisotropy according to the degree and direction of water molecule permeability in tissues. Fractional anisotropy (FA) is used to measure the directionality obtained in axon bundles as well as myelination. Increasing evidence has suggested that the low FA values in WM association areas are related to negative motor and cognitive functions in preterm infants .Nevertheless, few studies have been conducted to evaluate the correlations between WM connectivity as revealed by DTI and motor neurodevelopment of extremely low birth weight  infants with WM abnormalities , 8. TherThis study is part of a prospective research program on ELBW infants involving short- and long-term postnatal follow-up at the Hanyang Inclusive Clinic for Developmental Disorders in Hanyang University College of Medicine. The 72 ELBW infants (<1000 g) born and admitted to a level 3 Neonatal Intensive Care Unit at Seoul Hanyang University Hospital of South Korea between February 2011 and February 2014 were eligible for the study. The major exclusion criteria were congenital malformations or chromosomal anomalies. These infants were imaged during natural sleep without sedation using oral chloral hydrate.Prenatal and neonatal data were prospectively recorded, including gestational age (GA), birth weight, delivery mode, sex, twin status, Apgar at 5 min, maternal chorioamnionitis, and prenatal steroid use for each infant. Chorioamnionitis was defined by the presence of histologic chorioamnionitis or umbilical cord vasculitis of grade 2 or greater, using the grading system suggested by Salafia et al. . NeonataConventional magnetic resonance (MR) images and diffusion tensor images were obtained with a 3.0 T MRI scanner  with a six-channel SENSE head coil operating. Conventional MR images included sagittal and axial T1 spin-echo sequences  and axial T2 fast spin-echo (4500/90/3). The Philips Research Imaging Development Environment (PRIDE) Diffusion Registration tool (version 0.4) was used to calculate FAs of the diffusion tensor data after processing of the DT-MRI images. Region-of-interests (ROIs) measurements were performed to examine the regional distribution of FA values in 2-dimensional space. We reconstructed fiber-tracking in 3-dimensional space using PRIDE Fiber Tracking tool (version 4.1) and set 3 ROIs for the motor tract at the ventral part of the pons, the internal capsule and at the centrum semiovale to evaluate fiber connectivity. We didn’t include a tractography to analyze quantitatively but performed tractography itself to assess the connectivity and disruption of depicted motor tract.b = 800). Tracking was stopped when the FA in a pixel below 0.18 was reached to prevent streamlines from going into low anisotropy gray matter.Diffusion tensor images were sing a single-shot spin-echo planar sequence with a SENSE factor of two and an echo-planar imaging factor of 67 . Diffusivities were measured along 15 directions using an electrostatic gradient model , anterior internal capsule, posterior internal capsule, posterior thalamic radiation, and centrum semiovale Fig. .Fig. 1A Neurodevelopmental outcomes were assessed at a mean age of 18 ± 3.5 months (range: 15–23 months) with the Bayley Scale for Infant Development-III (BSID-III), which evaluates five distinct scales: cognitive; language, with receptive and expressive communication subtests; motor, with fine and gross motor subtests; socioemotional behavior; and adaptive behavior. The average BSID-III score in healthy infants and children is 100 ± 15.P-values < 0.05 were considered statistically significant. The study was approved by the Hanyang University Hospital Institutional Review Board, and written informed consent was obtained from the patients’ parents.Comparisons between groups were carried out by one-way Analysis of Variance or Kruskal-Wallis tests for comparison of continuous variables. Categorical variables were analyzed by Pearson’s chi-square test or Fisher’s exact test (both two-sided), as appropriate. To account for multiple comparisons, Bonferroni’s correction was considered. All statistical analyses were carried out using SPSS 17.0 (SPSS Inc.). n = 10) and refusals (n = 10), 32 patients who fulfilled the study criteria were enrolle. During the study period, 32 infants with available DTI data were evaluated for the regional distribution of FA values associated with WM injury with GAs ranging between 23 and 30 weeks and birth weights ranging between 760 and 1740 g. Thirty-two ELBW infants  underwent conventional MRI and DTI at a mean post-menstrual age of 36.5 ± 1.9 weeks. Ten of these infants developed WM abnormalities . Five of the ten infants with WM abnormalities  developed spastic CP . The infants enrolled in the DTI analysis were classified into three groups; no WM abnormalities, WM abnormalities without CP, and WM abnormalities with CP. Table P < 0.001).Seventy-two infants with ELBW were admitted during the study period, and 62 infants were included after parental consent was obtained. Eighteen infants were excluded due to instability during the MRI exam with poor results, and two infants were excluded due to insufficient data. Excluding deaths n = 0 and refp = 0.022), the ipsilateral posterior limb of the internal capsule (p = 0.019), and the ipsilateral centrum semiovale (p = 0.012) compared to those in no WM abnormalities group and WM abnormalities without CP group. Although there were no significant differences in the splenum of the corpus callosum between the study groups, the WM abnormalities with CP group had lower FA values compared to the WM abnormalities without CP group  and/or impaired cognition (four out of five children). The remaining five infants constituted the WM abnormalities without CP group. Four of these five children had normal development without delays of cognitive, motor and language functions as assessed with the BSID-III.This study demonstrated that DTI performed at term equivalent age shows different FA values in WM regions among infants with or without WM abnormalities associated with prematurity and/or CP. The motor outcome of the patients with WM abnormalities associated with prematurity was associated with low FA values in the DTI parameters of the genu of the corpus callosum, the ipsilateral posterior limb of the internal capsule, and the centrum semiovale at discharge in extremely low-birth weight infants.WM abnormalities associated with prematurity, which is the leading cause of CP, is estimated to occur in 10–15% of very low-birth weight  infants and is attributed to the developing brain’s vulnerability to hypoxic ischemic events . Follow-Great progress has been made in the past few decades in the approach to microstructural development with a novel tract-based analysis of DTI data in infants. DTI has good sensitivity and specificity to assess quantitative changes in the various brain microstructures during the developmental stage . ConventPartridge et al.  seriallyHowever, there have been few DTI studies about the predictive value of abnormal WM lesions prior to the manifestation of hemiparesis in preterm infants with high risk factors. Fundamental questions remain to be addressed to predict long-term developmental outcomes at term-equivalent age, limiting our ability to assess the therapeutic interventions needed during critical periods of development. DTI might add another piece to the puzzle of pathophysiology preceding developmental delay in high-risk preterm infants with WM abnormalities associated with prematurity. The early identification of candidates at risk of developing CP or abnormal WM maturation is helpful in selecting infants for potential therapeutic interventions in order to improve long-term outcomes. In the present study, infants having WM abnormalities in the presence of CP showed a decrease in the FA of diffusion tensor values at term-corrected age, particularly in the regions of the centrum semiovale, the posterior limb of the internal capsule, and the corpus callosum.Our findings are similar to the results of earlier studies. Murakami et al.  examinedThis study demonstrates low FA values of ROIs in DTI are related with later development of spastic CP in preterm infants with WM abnormalities. A quantitative approach using DTI in specific WM might provide prognostic values for the brain development in preterm infants. The value of DTI in predicting long-term infant neurodevelopmental outcomes should be analyzed in a larger cohort.


Inclusion criteria: low risk gestation, cephalicpresentation, single childbirth, delivered at term. Scheduled and urgent cesareanswithout labor were excluded. A descriptive and inferential analysis of thevariables was performed. the birth plan was mostly fulfilled in only 37% of the women. The group of womenwhose compliance was low  had a cesarean section rateof 18.8% and their children had worse outcomes in the Apgar test and umbilicalcord pH; while in women with high compliance (75% or more), the percentage ofcesareans fell to 6.1% and their children had better outcomes. birth plans have a low degree of compliance. The higher the compliance, the betteris the maternal and neonatal outcomes. The birth plan can be an effective tool toachieve better outcomes for the mother and her child. Measures are needed toimprove its compliance. The birth plan is atool that contributes to this fact, since it is a written document that the womanpresents before delivery to the professionals who will assist her and reflect herpreferences, expectations and fears about her own birthing process. The birth planfacilitates communication with professionals, improves women’s satisfaction, andpromotes their participation and decision-making in their own birthing processJust like the informed consent document, the birth plan is a supporting document togather the user’s will. The free and informed decisions of the users must be respected,regardless of the form and title given to it, even if they are expressed onlyverballyThe use of birth plans is recommended by institutions such as the World HealthOrganization (WHO), as it encourages a more natural process of childbirth and avoidsroutine intervention procedures, such as early amniotomy, systematic episiotomy andothersIn Spain, in the 1990s, several associations emerged against excessive intervention inchildbirth care which, since the middle of the last century, has been institutionalizedand subjected to an important degree of medicalization-,However, the use of childbirth plans is not exempt from controversy and may give rise tosome degree of conflict with professionals, who may see diminished see their autonomyand professionalismOn the other hand, there are some studies that found a lower rate of cesareansectionsIn Andalusia, Spain, following the Humanization of Perinatal Care Project in Andalusia,the health system offers the possibility of presenting a childbirth planFrom the knowledge that many of the petitions that women reflected in their birth planswere not met, it was hypothesized that the greater the compliance, the better would bethe outcomes after childbirth. The objective of this study was to know the degree ofcompliance of the proposals reflected in the birth plans and to determine theirinfluence on the main obstetric  andneonatal outcomes . This is a retrospective, cross-sectional, descriptive and analytical study carried outin third-level hospitals of the Public Health System of Andalusia. A third-level publichospital was selected in each province, the one with the highest coverage. The sampleconsisted of women who presented a birth plan at admission to the referral hospitalbetween January 2009 and January 2013. Data were extracted anonymously from thecorresponding medical records. The following inclusion criteria were considered: lowrisk gestation, cephalic presentation, single childbirth, delivered at term. Scheduledand urgent cesarean sections without labor were excluded. The sample size was determinedusing the Epidat software version 3.1. The final sample consisted of 178 clinicalrecords of parturient women.Sociodemographic and obstetric variables were analyzed to determine the characteristicsof pregnant women and the degree of compliance with the birth plan. For this purpose,the birth plans were carefully examined and the four most requested preferences duringthe labor process were extracted, accounting each one with 25%. These four requirementswere: avoiding use of oxytocin during labor, avoiding early amniotomy, freedom ofmovement during labor, therefore without continuous monitoring, and avoiding episiotomy.The variables that were evaluated were: proportion of cesareans and vaginal deliveries,Apgar test at 1 minute and 5 minutes, and umbilical cord arterial blood pH, consideringpH < 7.20 as pathological.t-test for quantitativevariables. An error α of 5% (p ≤ 0.05) was assumed, showing the exactp-values for each statistical test.A descriptive and inferential analysis of the variables was performed using theStatistic PASW software version 19. The qualitative variables were expressed in number(n) and percentages (%) and the quantitative variables expressed as mean and standarddeviation (SD). We used hypothesis contrast statistical tests according to the type ofvariable. For bilateral contrasts, the chi-square test was used, with Fisher’s exacttest in qualitative variables and Student’s The permission by the ethics committee of the different hospitals ensured the access andcompilation of clinical records data. The final sample consisted of 178 women’s medical records. Regarding the generalcharacteristics, it is worth noting that the mean age was 33.00 ± 4.32 years, with aminimum age of 19 and maximum of 42 years. The percentage of women with universitydegrees was 49.3%, of which 45% are from the health and education sector.The obstetric outcomes showed that 75% of women were primigravidae, 73% had spontaneousonset of labor, while the remaining 27% had induced labor. Moreover, 43% of the womenhad an episiotomy, another 43% received oxytocin during delivery, 34% of the womenunderwent amniotomy, and 70% received epidural analgesia. Seventy-six percent of thewomen had continuous monitoring and the remaining 24% had intermittent monitoring, sothey had freedom of movement. Among those monitored continuously, 68% were monitoredexternally, while 8% were monitored internally. The outcomes at the end of delivery wereas follows: 67% of the women presented normal or spontaneous delivery, 19% hadinstrumented delivery, and 14% had a cesarean section. Data on the fulfillment of the birth plan  showed tp=0.023.Eighty-four percent of cesarean sections occurred in the group of women with 50%compliance or less, while in the group of women with a high degree of compliance, only16% of cesareans occurred. The data are shown in When comparing the degree of compliance of the birth plan with the outcomes obtainedaccording to the type of delivery, it was observed that the percentage of vaginaldeliveries increased as the fulfillment of the birth plan increased. Thus, whencompliance was 50% or less, the proportion of vaginal deliveries was 81.3%, while whencompliance was greater than or equal to 75%, vaginal deliveries reached 93.9%. Regardingthe proportion of cesarean sections, when adherence was low ,the percentage of cesarean deliveries was 18.8%; while when compliance was high (75% orhigher), the percentage of cesarean sections dropped to 6.1%; p=0.024). There were no significant differences in the 5 min Apgartest. Regarding neonatal outcomes , childre,-,Analyzing the results on the degree of fulfillment of the birth plan among the women whopresented it, the majority (63%) had the plan fulfilled or performed with mostly 50% oftheir requests, moreover, only 37% of the women had their birth plans fulfilled for themost part, and of these, only 8% had their plans fully fulfilled. It is logical to thinkthat postpartum satisfaction will be directly proportional to the degree of fulfillmentof the expectations met and fulfilled, as many authors suggest-,The reasons for this low degree of compliance may be multiple, but it is necessary tomention here two main ones. First of all, as already mentioned, the course of the laborprocess is uncertain and can be complicated at any time, or unforeseen events may arisewhich may lead to a breach of the birth plan requirements and a change in the course ofevents. On the other hand, a certain tension can be generated between the parturient andthe professional who assists her, due to the non-acceptance of the loss of professionalautonomy; in these cases, the birth plan may act more likely as a barrier-,Regarding the results found, it is noteworthy that 84% of cesarean sections occurred inthe group of women with adherence to plan less than or equal to 50%, whereas in thegroup with a high degree of compliance, 75% or more, only 16% of all cesarean sectionswere performed. In this sense, although no studies have been found that directlycorrelate the fulfillment of birth plans with the outcomes, there are some studies thatconcluded that women with birth plans had a lower risk of cesarean sections,The neonatal outcomes of the present study show that the higher the compliance of thebirth plan, the better the Apgar score and the umbilical cord pH range. Other studies donot show any differences in the Apgar test between newborns of mothers with or without abirth planThe limitations of this study were mainly the heterogeneity of the caregiverprofessionals, as well as the heterogeneity of the birth plans themselves, since in somecases the institutionalized model is presented and in others, an original manuscript bythe woman herself.In conclusion, the birth plan has a low degree of compliance, since only 37% of thewomen who presented it were mostly fulfilled. However, there is a direct relationshipbetween obtaining a higher degree of compliance of the birth plan by obtaining betteroutcomes for both the mother and her child. Thus, as compliance with the birth planincreases, the cesarean rate decreases and the outcomes in the one minute Apgar test andthe umbilical cord pH improve.Implications for clinical practice: the birth plan can be an effective tool to favor amore natural and physiological delivery process, better communication withprofessionals, greater control of the labor process, better obstetric and neonataloutcomes and greater satisfaction. Improving the degree of fulfillment of the birthplans is key in obtaining these outcomes. Policies are needed to encourage the use ofbirth plans and to improve its implementation and compliance.


Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There’s a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than population-based growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby. Birth weight and birth weight centiles were analysed for 88 women with SCD  and 176 controls (HbAA). Statistically significant differences were seen in the mean birth weight  and the mean birth weight centiles . We conclude that SCD is a risk factor for having a smaller baby. The clinical care for Sickle Cell Disease (SCD) has vastly improved the quality and longevity of those affected. Pregnancies in this cohort, however, still carry a greater risk of unfavourable pregnancy outcomes . The majn = 1,523, HbSC n = 331, unspecified SCD genotype n = 24,969) showed a greater relative risk (RR) of small for gestational age (SGA) when analysed against women with normal haemoglobin (HbAA)  [n = 118 HbSC and n = 110 HbAA pregnancies showed an increased rate of low birth weight (LBW)  [n = 55, HbSC n = 44, other SCD n = 11, unknown SCD genotype n = 3) based on data extracted from the United Kingdom Obstretric Surveillance Study (UKOSS) showed an overall higher prevalence of LBW in babies born to mothers with SCD  compared to HbAA mothers, as well as an increased rate of LBW in babies born to HbSS versus HbSC mothers  [A meta-analysis of 26,823 SCD pregnancies , ethnicity and the number of previous births; and infant outcomes: sex and gestational age at birth. Data were extracted from an electronic clinical database . The midwife attending the delivery had recorded data on the database. These data were used to generate a customised birth weight prediction, which was compared to the infant’s actual weight at birth using the UK Gardosi Bulk Centile Calculator Version 6.6 . This veData were only included from singleton pregnancies, because pregnancies involving more than one foetus are susceptible to considerable foetal growth and weight differences ,11. In aCustomised growth chart calculators control for healthy growth variations due to: ethnicity, parity, maternal habitus, gender and gestational age at delivery. Population-based growth charts thus do not accurately distinguish between permissible  and pathologically small neonates, whereas customised growth charts do . Customith centile for gestation [Women were matched by age at delivery, parity and ethnicity to control for birth weight variations pertaining to ethnicity and parity. Although this is a cohort study, the matching allowed the control population to be as representative of the study population in as many aspects as could be controlled for, so as to enable any differences in the results to be representative of the difference in haemoglobin status rather than normal physiology . The uppestation .The study population incorporated all eligible women with SCD and the control population included all eligible women without SCD. The SCD group was stratified according to SCD type into HbSS and HbSC. Statistical analyses were made comparing SCD group against the control group, and the stratified HbSS and HbSC groups against the controls, using Stata 14. Given the heterogeneity of SCD, the purpose of the latter was to enable specific analysis of the impact on haemoglobin status on foetal growth [Statistical differences and 95% confidence intervals were generated using logistic regression to analyse the birth weight and birth weight centiles in the study and control groups. Differences in the mean maternal age, BMI, gestational age and birth weight were estimated along with their 95% confidence intervals. T-value was performed to obtain the p-value for the difference, and the null hypothesis defined as a difference being equal to 0. For variables expressed as proportions  we performed logistic regression to identify any differences in the proportions for the SCD and HbAA group ,7,14,15.2 (22.5 kg/m2 in HbSS and 28.3 kg/m2 in HbSC groups) and 27.3 kg/m2 in the control group . There were no statistically significant differences in the rates of SGA or LBW amid the SCD and HbAA groups Birth weight and birth weight centiles were analysed for infants born to 88 women with SCD  and 176 controls (HbAA)  th centile) was significantly lower than the controls (42.2nd centile) with a difference of 9.4 centiles  The main differences between the SCD and control group were the mean birth weight and mean birth weight centile. The overall mean birth weight for the SCD pregnancies was 2918g compared to a mean birth weight of 3176g for the controls. The mean birth weight of the neonates born to SCD mothers was significantly lower at 258g below that of the HbAA counterparts . In keeping with this, the mean birth weight centile for the SCD deliveries (32.8th week of gestation) was 10.2% (n = 9) for the SCD group (95% CI = 5.3%-18.7%) and 9.1% (n = 16) for the control group (95% CI = 5.6%-14.4%) [The preterm birth rate  and mean birth weight centiles . Inadequate foetal development and/or premature labour can cause LBW [problems . Pregnanin utero .A neonate may exceed the threshold for SGA and still be growth restricted. IUGR reflects an infant who has been unsuccessful in attaining his or her personal optimal growth . Our finGestational age at delivery is influenced by: maternal age at delivery, socioeconomic status, pathology, number of previous births, demographics, a history of preterm birth and smoking. Mothers of Black and Asian ethnicity have been shown to deliver earlier compared to white counterparts . LBW hasOur SCD group had a significantly lower mean BMI than our controls Alarmingly, a number of the controls were overweight (BMI between 25 and 29.9) or obese (BMI ≥30) . The BMIth centile for birth weight for gestation at delivery and sex), and heart disease in later life, respectively [Maternal obesity during pregnancy exposes the foetus to increased morbidity and mortality in the short- and long-term, including perinatal death and being large for gestational age (LGA)  to optimise the baby’s prospects. Our findings emphasise the importance of regular detailed routine non-invasive monitoring for indicators of IUGR in the management of all SCD pregnancies .Our study identifies several areas for future research. Firstly, problems with the placenta may underpin the IUGR ,18. The Asymmetrical IUGR affecting the third trimester has been seen in SCD pregnancies . A studySecondly, the impact of SCD, notably HbSS on preconception BMI and pregnancy weight gain . ThirdlyThis study is the first to quantify the impact of SCD on birth weight and birth weight centiles using customised growth charts. We conclude that SCD is a risk factor for smaller babies .


In low income countries, many low birth weight newborns often miss the chance for survival sooner or later. Others who survive would also face increased risks in later life. Though not adequately documented in Ethiopia, maternal factors pose the main risk. This study was aimed to estimate the proportion of low birth weight among term singletons without congenital malformations and factors associated with it in Wolaita Sodo town in South Ethiopia.P < 0.05 were reported.We did a facility based survey involving 432 postpartum women with their term newborns. Data was collected through face to face interview from March to April in 2016. The outcome measure was newborn birth weight. Bivariate logistic regression was applied to look for crude associations. Multivariate logistic regression analysis was done to adjust for potential confounders to identify independent predictors. Adjusted Odds Ratio (AOR) and 95% confidence intervals (CI), and statistical significance at The proportion of term low birth weight was 8.1% in the study area. Women who had less education , house wives  and not frequently consuming fruits during pregnancy  had a higher risk of having term low birth weight newborns. We documented a lesser odds of those from rural settings to have low birth weight newborns as compared to their counter urban equivalents .Dietary counselling to pregnant mothers specific diet and nutrition including fruit diets in particular might contribute to reduce the risk of term low birth weight. Better education might have enabled women to prefer diets and their job engagements might also have capacitated them to decide on dietary preferences.The online version of this article (10.1186/s12884-018-1789-y) contains supplementary material, which is available to authorized users. If a newborn weighs less than 2500 g at birth, it is termed as low birth weight (LBW) . A low bAn estimated 13% all babies each year in Sub-Saharan Africa (SSA) are born LBW . AccordiIn Ethiopia, most commonly used data on birth weight of the newborns are often based on national survey indirect indicators. However, the national data is known for its limitations including sampling strategies which would not be assumed to be representative of the socio-economic disparities and cultural diversities across the country. Though the proportion of skilled childbirth attendance is increasing in Ethiopia, we lack adequate evidence on maternal factors which would potentially predict birth outcomes of the newborns. This is so limited particularly in South Ethiopia which is characterized by a diverse culture and dietary practices. Thus the proportion of low birth weight in health facilities has been least documented in South Ethiopia.A densely populated Wolaita area in south Ethiopia –19, manyWolaita Sodo town is an administrative capital for the Wolaita zonal administration in South Ethiopia. It is located at 380 km south from Addis Ababa. The town has 3 sub-cities; 11 lower administrative units. It had a census projected population of 110,659; 48% were female.One government hospital and another private one, 3 health centres, 11 health posts and 21 other private health facilities deliver health services to the population in the town. Out of all facilities; only health centres and hospitals are staffed to attend skilled childbirth [We did a facility based cross-sectional study involving postpartum mothers and their newborns through birth records from March to April in 2016.All postpartum mothers and their newborns in government health facilities in Wolaita Sodo town were the source population. Consecutively recruited 432 mother-newborn-pairs were studied. Term newborns (born at 37 weeks or later of gestation) and singletons were included. Birth outcomes such as congenital malformations, multiple births, and stillbirths, and postpartum mothers with unknown last normal menstrual period were excluded.A sample size of 451 was calculated with the following assumptions: 22.5% expected proportion of low birth outcome which was taken from similar Ethiopian study , 95% conBirth weight of a term singleton newborn was an outcome measure. It was considered low birth weight if the newborn weighed less than 2500 g. Birth weight measurement was taken within an hour after birth .Socio-demographic and socio-economic: maternal age, educational status, occupation, residence, family income and newborn’s sex .Diets and supplements: consumption of any additional meals and supplements such as iron and folic acid during pregnancy .Maternal morbidity and previous obstetric histories: history of hypertension, diabetes mellitus and infections during pregnancy , pregnanMaternal health service utilization: antenatal care (ANC), gestational age at first ANC visit, and dietary counselling in ANC , 23. WheMaternal nutritional status: Mid Upper Arm Circumference (MUAC) of mothers. Whereas, MUAC less than 23 cm centimetres defined the women as undernourished .We adopted a structured questionnaire from relevant articles and related literatures  were aged 20–34 years. The majority 374 (86.6%) had some level of formal education and 187 (43.3%) were housewives. About two-third, 291(67.4%) were urban and a third were rural residents (Table One hundred eighty (41.7%) of mothers were primiparous. About a third, 83 32.9%) of the women gave birth to the current newborn within two years (≤24 months) after a previous child birth. Thirty four mothers (7.9%) had previous abortion and 18 (4.2%) had still birth. One hundred twenty-five (28.9%) mothers had some medical problems during recent pregnancy. The majority, 396 (91.7%) had at least a visit for antenatal during recent pregnancy; 376 (94.9%) of made their first visit during first trimester of gestation. A little higher than half, 210 (53%) had at least four ANC visits and 290 (73.2%) mothers affirmed for getting dietary advice during ANC follow-up  mothers had MUAC less than 23 cm (undernourished). Three hundred fifty-five (92%) took iron and folic acid supplements at least once and 264 (61.1%) got less than 90 tablets during recent pregnancy. About two-third, 293 (67.8%) consumed at least one additional meal to their usual meals. Mothers involved in this study frequently consumed cereals 258 (59.7%) from food groups (Table 8.4% mothThe proportion of term low birth weight in this study was 8.1% 35/432). The mean weight of the newborns was 3532 g with standard deviation of 565. Mothers with less formal educational status and housewives had about six times at higher risk of giving birth to low birth weight newborns  and . Mothers who consumed fruits rarely (less frequent than daily) had also a higher risk to give birth to term LBW . On the other hand, rural residents had a lower risk of giving birth to low birth weight newborns as compared to those from the nearby urban dwellers   and elsewhere (10.6%) , 29. It % and elsIn consistent with studies from India, Tanzania, and Sudan, lower level of maternal education was documented in this study as a positive predictor of low birth weight , 6, 33. Unlike many other study findings, this study documented that rural residents had a lower risk to have low birth weight babies as compared to those from nearby urban settings. This finding disagrees with similar study findings from Tigray (Northern Ethiopia) and Bale (South east Ethiopia) hospitals in Ethiopia , 11, 35 Housewives had much higher odds of giving birth to low birth weight babies as compared to those who had some occupational engagements. This finding is in difference with similar studies South East in Ethiopia as well as Tanzania , 34, 35.Mothers who did not consume fruits daily during pregnancy had much higher odds of giving birth to low birth weight as compared to those who did so. This was in agreement with a similar study in Nepal . This miThis study was limited to health facilities in scope and used a crossectional data. Thus mainly maternal side predictors of term low birth weight were assessed. Moreover, the time allotted for recruiting participants was limited though we assumed standard procedures of sample size calculation. The estimate might be better representative if a longitudinal follow-up data were used. Certain level of recall bias was expected with regard to menstrual dates and dietary habits; health workers conscious on cultural issues collected the data to reduce recall bias. Though all mothers attending delivery service with ANC follow up were ahead screened for HIV, we could not access this information due to limitations out of our scope. We have no data on other covariates such as food security and a reliable wealth data.Though it would or would not be possible to bring all child bearing or potential mothers with less education to school; alternative opportunities of empowering women could be done. Occupational engagements of the women might also contribute to empower them on decision making capacities particularly on diet and health care.Skilled counselling to diet during pregnancy including intake of fruits would benefit the women. Formal education when feasible and alternatively equivalent approaches targeting on diet and health care utilization would benefit. Moreover, we recommend community based data of birth weight through longitudinal studies for a better estimation of the prevalence of low birth weight.Additional file 1:Questionnaire: Term low birth weight study, Wolaita Sodo. (DOCX 23 kb)