Non-nutritive sucking habits (NNSH) are very common during childhood. However, if these habits were maintained for 36 months of age or more, they are considered to be prolonged (PNNSH) and can cause occlusal, physiological and esthetic changes. There is controversy about their prevalence and whether perinatal, social, demographic and health characteristics influence their onset and duration. So, the objectives of this study are to estimate the prevalence of PNNSH and to evaluate perinatal, early life and school age factors associated with their occurrence in children.A sample of 1,463 children aged 7–11 years born in Ribeirão Preto (RP-1994) and São Luís (SL-1997/98), Brazil, was reevaluated at school age in 2004/05. Birth weight, gestational age and perinatal variables were obtained at birth. Type of feeding, occurrence and duration of finger and pacifier sucking were recorded retrospectively at school age. PNNSH were defined when persisted for 36 months of age or more. Crude and adjusted prevalence ratios (PR) were estimated by Poisson regression .Prevalence of PNNSH was higher in RP (47.6%) than in SL (20.2%) – (p < 0.001). Perinatal variables were not associated to PNNSH, whilst female sex  and bottle feeding for 24 months or more  were risk factors in both locations. Breast feeding for 12 months or more  was associated with lower prevalence of PNNSH in both places. In SL, children whose mothers lived in consensual union (PR = 1.62) and worked outside the home (PR = 1.51) showed higher prevalence of PNNSH compared to their counterparts.Prevalence of PNNSH was high especially in RP and was not associated with perinatal variables. In both cities there was an association between female sex, shorter breast-feeding duration, longer bottle feeding duration and higher prevalence of PNNSH. Sucking habits are actions acquired by the frequent repetition of conscious or unconscious neuromuscular activities regulated by reflex arches originating from psychological needs ,2. They Non-nutritive sucking habits (NNSH) are very common during childhood ,6. HowevBreast-feeding has been associated with a lower occurrence of these habits -13, wherMost of the studies on this subject have been conducted on small, convenience samples with a cross-sectional design and with little or no control for confounding factors ,11,12,16per capita income of RP is twice that of SL [The data used were from two cohort studies ,18 conduat of SL .The RP cohort consisted of 2,846 liveborns delivered by mothers residing in the municipality at the 10 city hospitals from April to August 1994, representing 99% of all live births during the period. Losses corresponded to less than 5% of births . The SL Samples of the two cohorts were reevaluated at school age, with the subjects being divided into five birth weight groups: very low birth weight , low birth weight , insufficient birth weight , normal birth weight , and high birth weight . Children in the weight groups including a smaller number of newborns  were oversampled in order to increase the study power. At reevaluation, RP children were 10 and 11 years old and SL children were seven to nine years old. The children in the two cities were searched and located in the schools. All parents or persons responsible for VLBW, LBW and HBW children and for one in each three children in the IBW and NBW groups were invited to participate in the study by telephone or mail. In SL, after exclusion of multiple births (n = 50), stillborns (n = 48) and infants who died in the first year of life (n = 65), 926 children were eligible for follow-up. Of these, 673 were evaluated, five of them being VLBW, 76 LBW, 19 HBW, 134 IBW, and 439 NBW, representing a follow-up rate of 72.7% .In RP, after exclusion of multiple births (n = 65) and infants who died in the first year of life (n = 48), 1,150 were eligible for follow-up. Of these, 790 were evaluated, 24 of them being VLBW, 145 LBW, 174 IBW, 419 NBW, and 28 HBW .Sample size calculations were performed in Epi-Info software, version 7.0 . A sample of 676 children in each city has an 80% power to detect significant prevalence ratios (PR) equal to or higher than 1.22, considering a 50% prevalence of PNNSH and a 1:1 ratio between exposed and unexposed individuals, with a 5% probability of type I error. Furthermore, a sample of 637 children in each city has an 80% power to detect significant prevalence ratios (PR) equal to or higher than 1.38, considering a 50% prevalence of PNNSH and a 1:9 ratio between exposed and unexposed individuals, with a 5% probability of type I error.In addition, power calculations were performed in Stata 13.0 software  using data from São Luís because the sample size there was smaller than in Ribeirão Preto. Contrasting 81 low birth weight children with their 592 non-low birth weight counterparts, the power to detect significant prevalence ratios (PR) equal to or higher than 1.38, considering a 50% prevalence of PNNSH, with a 5% probability of type I error was 89.49%. Contrasting 115 children with breast feeding duration ≥12 months with 275 children breastfed for <6 months, the power to detect significant prevalence ratios (PR) equal to or higher than 1.38, considering a 50% prevalence of PNNSH, with a 5% probability of type I error was 87.69%.The children were reevaluated at school age by means of a standardized questionnaire applied to the parents or persons responsible for them, containing questions about child’s social, demographic, general and oral health characteristics.The dependent variable, PNNSH, was defined as pacifier and/or finger sucking maintained for 36 months of age or more ,24. The The independent variables collected at birth and used for analysis were: maternal age (in completed years), maternal schooling (in completed years of study), monthly family income (minimum wages), maternal marital status , maternal smoking during pregnancy (yes if she smoked at least one cigarette a day), mother’s work outside the home (yes and no), and parity , preterm birth , LBW (yes if <2500 g) and child’s sex. The following variables were obtained at school age: duration of breast-feeding , duration of bottle feeding  and current occupation of the family head .Due to the oversampling of VLBW, LBW and HBW cases, the estimates were corrected by weighting using the variables "birth weight" and "preterm birth". Complex sample design was considered in all statistical analyses (sampling stratified by birth weight and application of sampling weights) .The associations between the dependent variable and the remaining variables were determined by the chi-square test with α = 0.05. Crude and adjusted prevalence ratios (PR) with their respective 95% confidence intervals (95%CI) were calculated by Poisson regression with robust adjustment of variance since the prevalence of PNNSH was more than 10% in both cities . We testTwo models were fitted: Model 1 was adjusted for birth variables and Model 2 included birth and school age variables. The tables show the unweighted absolute frequencies and the weighted proportions of the variables. Each variable presented percentage of missing values <5% in both cities. So, we performed analyses excluding missing values. The Stata 9.0 package was used for statistical analysis.At birth, consent for the study was requested from the hospitals’ directors and mothers were interviewed after giving informed verbal consent. At school age, the parents or persons responsible for the children signed the informed consent form after reading the plain language statement. The study was approved by the Research Ethics Committees of the University Hospital, Ribeirão Preto Medical School, University of São Paulo (HCFMRP-USP) and of the University Hospital of the Federal University of Maranhão (HU-UFMA).The prevalence of PNNSH differed significantly between the two cities, being higher in the more developed city – RP  than in the less developed one – SL . Missing data regarding PNNSH was observed in 14 subjects in RP and 19 in SL.The percentage of teenage mothers was higher in SL (29.3%) than in RP 16.6%) whereas the percentage of maternal age ≥35 years was higher in RP (11.5%) than in SL (4.6%). Low schooling (≤4 years of study) was observed in 21.6% of RP mothers and in 15.9% of SL mothers. However, a higher percentage of high (>11 years) schooling level was observed in RP (13.1%) compared to SL (1.8%). Percentage of children from families earning ≥6 minimum wages per month was higher in RP (44.2%) than in SL (19.9%). While in RP 2/3 of the mothers were married, consensual union predominated in SL. The prevalence of smoking during pregnancy was almost five-fold higher in RP than in SL. More than 1/3 of RP mothers reported that they worked outside the home, compared to 1/5 of SL mothers. The proportion of five children or more was quite close in the two cities, and being an only child occurred in 40.3% of cases in RP and in 46.5% in SL. Preterm birth (14.9% in RP and 8.7% in SL) and LBW rates (10.6% in RP and 5.8% in SL) were higher in RP than in SL. Boys represented a little more than half the sample in both cities  and the proportion of bottle-fed children during 24 months or more was expressive, especially in RP (59.4%). In RP, 43.4% of the family heads were unskilled manual workers, as compared to 58.0% in SL , who were primiparae or who gave birth to boys compared to the eligible group that did not participate. There was no difference between participants and non-participants regarding maternal age or marital status. Differences in birth weight and preterm birth were observed due to the study’s complex sampling design and were corrected by weighting .Recall errors or telescoping effect may have been present because feeding habits and PNNSH were recorded retrospectively. Interactions terms were not added to the models. Sample size calculation and power estimation did not take into consideration the weighted estimates derived according to "birth weight" and "preterm birth" and were based on the chi-square test and not on Poisson regression. Thus the real study power might have been somewhat lower than estimated.The present study is highly relevant by investigating a topic that has not been fully elucidated yet, by being a population-based cohort study involving two socioeconomically contrasting regions and due to the fact that VLBW, LBW and HBW were oversampled, a fact that increased the study power. In addition, it revealed that some factors commonly reported to be associated with finger and pacifier sucking at some time in life, such as maternal schooling ,16, mateThe prevalence of PNNSH was high, especially in the more developed location, and perinatal variables  were not associated with it. Shorter breast-feeding duration and longer bottle feeding duration were consistently associated with a higher prevalence of PNNSH. Nutritional suckling feeding habits at the beginning of life seem to be predictors of PNNSH at school age.The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.MMN, CSAF and FFPF analyzed the data and wrote the manuscript. AAMS, MCPS, MAB and HB conceived the research questions of the study, supervised the data collection of the study and were involved in critical revisions. Besides, they had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. EBAFT was involved in critical revisions and data analysis. All authors have read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/14/743/prepub


Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent.We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight , length , and head circumference .Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes.We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length . Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length .This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations.Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environ Health Perspect 124:1084–1092; http://dx.doi.org/10.1289/ehp.1409362 Organophosphorous (OP) pesticides, a widely used class of insecticides, have been the subject of concern in recent years because of their potential for developmental and neurobehavioral toxicity . Two comSeveral OP pesticides have been associated with reduced fetal growth in rodent studies , but stuPON1 gene whose allele frequencies vary significantly in different racial groups , whereas SNPs at the 192 position in the coding region affect the catalytic efficiency of that enzyme in detoxifying OP pesticides with 192QQPON coding for the enzyme with the lowest efficiency , measurement of OP exposure , variability in OP mixtures , and patterns of exposure  across studies. Other challenges to integrating these disparate results include the diverse racial/ethnic compositions of these cohorts, which contribute to differing frequencies of key genetic modifiers, among other sources of heightened susceptibility. For example, paraoxonase (PON) is an enzyme that plays a key role in metabolism and detoxification of some OP pesticides . Paraoxol groups . SNPs atficiency .PON1 genotype and race/ethnicity, we pooled data from four previously published longitudinal studies—the CHAMACOS, HOME, Columbia, and Mount Sinai cohorts. We hypothesized that DAP metabolites would be inversely associated with fetal growth, and that this effect would be especially prominent in infants with the susceptible PON1 genotypes with lower enzyme concentration and catalytic efficiency.To explore relationships between prenatal OP exposure and birth outcomes and potential modification by the The study sample combined participants from cohorts that measured urinary DAP metabolites during pregnancy. DAP concentrations from the CHAMACOS, HOME, and Mount Sinai cohorts have been previously reported . DAP conFor the main analysis, we excluded women with hypertension, diabetes, and other pregnancy complications that might affect fetal growth; twins and multiple births; stillbirths and neonatal deaths; and women providing urine samples that were dilute (< 10 mg/dL creatinine). The pooled data set included 1,235 women with urinary DAP measures during pregnancy and birth outcome data from each cohort: 484 women from the CHAMACOS study, 328 women from the HOME study, 82 women from Columbia, and 341 women from Mount Sinai. Informed consent was obtained from all women, and study procedures were approved by the institutional review boards at each research institution.In each cohort, mothers were interviewed during pregnancy in their preferred language (English or Spanish). Data collected in common across the four cohorts included demographic information , behavioral factors , and pregnancy health . Household income was not collected in one cohort (Mount Sinai) and thus could not be included in the pooled data set; because maternal education level was collected in all cohorts, it was used as a proxy for socioeconomic status.Infant weight, length, and head circumference at birth were abstracted from medical records at each location. Gestational age at birth was calculated by maternal report of last menstrual period (HOME study) or abstracted from medical records . Because Columbia and Mount Sinai measured OP exposure in a late stage of pregnancy, there was a truncated range in gestational age outcomes and few preterm births in these cohorts, limiting power to detect associations with gestational duration. Thus, gestational age at birth was examined as a covariate in the models of fetal growth, but not as an outcome in the pooled analyses.10-transformed for analysis. For the Columbia and Mount Sinai cohorts, the results of the single urinary measurements were used; for the HOME and CHAMACOS studies, the two measurements during pregnancy were averaged. The correlations between the two ΣDAP concentrations during pregnancy were 0.16 and 0.25 for CHAMACOS and HOME, respectively.In each cohort, spot urine samples were collected from pregnant women at the time of interview. This included two urine samples from women in the CHAMACOS  and HOME  cohorts and one urine collection from women in the Columbia  and Mount Sinai  cohorts. All urinary DAP measurements were conducted by the same laboratory at the Center for Disease Control and Prevention using gas chromatography–tandem mass spectrometry (GC-MS/MS) and quantified using isotope dilution calibration . Limits 192PON1 and –108PON1 genotyping was conducted separately at each research center using polymerase chain reaction (PCR)–based methods using umbilical cord blood for children and maternal blood. Genotyping methods have been previously published for the CHAMACOS cohort , and mixed-effects models did not have significantly better performance based on likelihood ratio tests (α = 0.05), so estimates from mixed-effects models are not reported.10 transformed) variables. All models controlled for cohort, sex, self-identified race/ethnicity , country of origin (USA vs. other), maternal education (< high school vs. ≥ high school), parity (primiparous vs. multiparous), smoking during pregnancy (yes vs. no), marital status (married/living together vs. other), and maternal age (continuous) . We compared models with and without the cross-product terms using Wald tests to examine overall categories of each potential modifier rather than category-by-category tests of interaction. We considered interaction to be statistically significant at α = 0.1. Stratified analyses were conducted according to cohort, race/ethnicity, and maternal and child PON1 genotype using separate models to obtain stratum-specific estimates. Because of the small size, the race/ethnicity category of “other” was omitted from stratified models, although it was included in the models with interaction terms. PON1 genotype was the most commonly missing variable, so the sample size was reduced for these interaction models .Creatinine-corrected, urinary DAP metabolites were considered as continuous (logtinuous) . Covariaa) limiting analyses to nulliparous women, b) limiting to term births, c) treating values < LOD as LOD divided by the square root of 2, d) classifying women identifying as Hispanic black (e.g. Dominicans) as black rather than Hispanic, e) including women with pregnancy complications such as hypertension and diabetes, f) using DAP concentrations that were not corrected for creatinine, and g) using only one (late pregnancy) DAP measurement from the HOME and CHAMACOS cohorts. All analyses were conducted in Stata 13.After constructing final models, we conducted sensitivity analyses including The four cohorts differed on every characteristic measured, including racial/ethnic composition, country of origin, maternal education, and marital status . The Colp-values ranged from 0.11 to 0.85; No associations were seen between total urinary ΣDAP, ΣDEP, or ΣDMP and birth weight, length, and head circumference in the pooled cohort . AssociaPON1 genotypes, so we present results stratified by child  was seen for race/ethnicity , sex da for non-by child  and mateIn models stratified by race/ethnicity , higher PON1 SNPs differed among the four cohorts . Interaction terms for genotype × DAPs were statistically significant in the models of ΣDEP on birth weight (p = 0.08) and ΣDAP and ΣDMP on length . With infant 192PON1 genotype, we observed negative associations of length and ΣDAP  and ΣDMP  among the RR group. Positive associations were seen with head circumference and ΣDAP  and ΣDMP  among the heterozygous QR group. No statistically significant associations were seen for DAPs and birth outcome stratifying by maternal PON1 genotype , except for a positive association of total ΣDEP and head circumference  in mothers with the 192QRPON1 genotype. Interaction terms for genotype × DAPs were statistically significant in the models of ΣDAP and ΣDMP on head circumference (p = 0.09 for both), again with positive associations seen in the heterozygous 192QRPON1 genotype, although no associations were statistically significant. Maternal 192PON1 genotype was not available for Columbia participants, and no maternal PON1 genotypes were available for HOME participants.The distribution of maternal and child  cohorts  and was thnicity . Analysegenotype , revealen = 638) or term births  or when women with pregnancy complications (n = 103) were included (data not shown). Results were also similar when the DAP concentrations were uncorrected for creatinine, when values < LOD were assigned LOD divided by the square root of 2, and when only one late pregnancy measure of urinary metabolites was used for each woman (data not shown).In sensitivity analyses, results did not change substantively when the sample was limited to primiparous women , suggesting that we cannot completely discount the possibility of residual confounding.We hypothesized that we might see inverse associations of urinary OP metabolites with birth outcomes in mothers or children with the more vulnerable genotype . In the enotypes . Howeverenotypes . In the genotype . We had In addition to racial and ethnic differences, the cohorts also varied in sources and routes of OP pesticide exposures, including food, home pesticide use, and agricultural drift or take-home exposure. Thus, urinary DAP concentrations may reflect different exposures in each cohort, limiting their interpretation in the pooled data set. In the farmworker CHAMACOS population, urinary DAPs likely represented a combination of agricultural, residential, and dietary exposure, a different mix of pesticides than would be experienced by the low-income, urban Columbia and Mount Sinai populations who were presumably exposed only through residential and dietary routes, or the more affluent HOME study participants who were enrolled after the residential ban and likely exposed mainly through diet. The HOME participants had relatively high DAP levels considering that their exposure was mainly dietary, suggesting that they may have had higher fruit and vegetable consumption, a very different route of exposure than women who may be exposed from home pesticide use.Not all of the six urinary DAPs were equally detected. The proportion of women with values below the detection limit in the pooled sample ranged from 9% for DMTP to 78% for DEDTP. Individual OPs do not necessarily devolve to all three DE or DM metabolites—for example, malathion devolves to DMP, DMTP (dimethylthiophosphate), and DMDTP (dimethyldithiophosphate), whereas oxydemeton-methyl devolves only to DMP and DMTP —and it iAlthough urinary DAPs are a useful biomarker of OP pesticide exposure, they have limitations. OPs have short half-lives in the body and show considerable intra-individual variability over time; thus, urinary DAPs represent short-term rather than ongoing exposure. DAPs are nonspecific metabolites, and not all pesticides that devolve to the same metabolite are equally toxic; for example, both oxydemeton-methyl and malathion devolve to DMP metabolites, but the former is much more toxic . AlthougOne strength of this study is its large sample size, which allows for better examination of race/ethnicity and genetic variability than in the more homogenous, individual cohorts. Methodologies were similar between cohorts and tests of interaction by cohort failed to reject the hypothesis of homogeneity by cohort. Analyses in our pooled cohort confirmed earlier findings of associations of OP exposure (as measured by DAPs in urine and chlorpyrifos in blood) with decreased birth weight in non-Hispanic black women, but not in whites or Hispanics . In gene–108CCPON1 and 192RRPON1 genotypes. However, this study also illustrates the limitations of pooling data when the population demographics and exposure patterns for biomarkers of exposure with a short half-life differ across cohorts. Although pooling data from multiple cohorts is tempting, careful consideration must be given to the interpretation of the exposure measures in each cohort and whether rank order is maintained and remains meaningful across the pooled cohort. In some cases, individual cohort studies with homogeneous populations may be preferable to pooled data.Overall, this study does not support associations of OP pesticide exposure during pregnancy with decreased weight, length, or head circumference at birth, except in black women and possibly infants with the Editor’s Note: In the Advance Publication, the symbols in the figure legends for (749 KB) PDFClick here for additional data file.


Birth weight is an important determinant of child survival and development. So far, the prevalence and traditional maternal feeding practice correlates of low birth weight have not been explored well in Ethiopia. Therefore, the purpose of this study was to determine the prevalence and associated factors of low birth weight among mothers who delivered at governmental hospitals, Northern, Ethiopia.p < 0.05. For the qualitative study design, following iterative hearing of the discussions verbatim interpretation was done & categorized in to themes and finally triangulated with the quantitative results.A cross-sectional mixed study design was carried out in 3 zonal hospitals among 308 mothers and their respective live born baby consecutively using interviewer administered piloted questionnaire and 3 focus group discussions were conducted for the qualitative part. The mothers were interviewed and assessed within 6 hours of delivery; all babies were weighed on standard beam balance from Aug 2 to Sep 12. Data were entered, cleaned and analyzed using SPSS version 16.0. Bivariate and multivariate logistic regression was employed to identify the predictors at The prevalence of low birth weight was found to be 14.6 % (95 % CI = 12.56-16.61) and the mean and standard deviations of the birth weights were 3094.9 ± 587.6 grams. Low birth weight was associated with rural place of residence (AOR = 4.34 (95 % CI = 1.99-9.48)), preterm birth/gestational age less than 37 weeks (AOR = 18.5 (95 % CI = 4.94-69.4)), presence of any chronic medical illness (AOR = 5.3 (95 % CI = 1.12-25.45) and maternal weight <50 kg (AOR = 2.26 (95 % CI = 1.06-4.80)). It was found that tradition of selection and preference of nutritionally poor food items during pregnancy was deep-rooted in the community.The prevalence of low birth weight was found to be high and it was associated with rural place of residence, gestational age <37 wks, presence of any chronic medical illness & maternal weight <50 kg. Emphasis should be given to nutritional counseling and disease specific ANC provision by skilled health professionals; Discussions with the community and religious leaders are mandatory aspect on the tradition of feeding of pregnant mothers to tackle the problem. This study also calls for community based further studies. The World health organization (WHO) defined low birth weight (LBW) as weight at birth of less than 2,500 grams. This practical cut-off for international comparison is based on epidemiological observations that infants weighing less than 2,500 grams are approximately 20 times more likely to die than heavier babies . The preLow birth weight is associated with many socio-economic factors such as residence , mother’s age and occupation, birth order, the family’s income and many maternal conditions such as nutritional status, mother’s educational and health status . Known fMore than 20 million infants worldwide, representing 15.5 percent of all births are born with low birth weight, 95.6 percent of them in developing countries. The level of low birth weight in developing countries 16.5 % is more than double the level in developed regions that is 7 % .In Ethiopia different studies have reported the prevalence of LBW from live birth hospital records, the prevalence of low birth weight was around 11 % , increasInstitution based cross-sectional concurrent quantitative-qualitative study design was used to describe the magnitude and associated factors of LBW and the socio-cultural factors were described using qualitative study design.Tigray forms the northernmost reaches of Ethiopia, and is located between 36 degrees and 40 degrees East longitude. Its North-South extent spans 12 and half degrees to 15 degrees north. It is bordered by Eritrea in the North, Sudan to the West, Amhara national state to the Southwest and Afar of Ethiopia to the East. Tigray has an estimated population of 4,565,000. The region has health service coverage of 83 %. Central zone is one of the six zones and it is around 1024 KMs away from Addis Ababa, capital of Ethiopia. Has a total population of 1,245,824, of whom 613,797 were men and 632,027 were women; 176,453 or 14.16 % are urban inhabitants [The study was conducted from Aug 2 to Sep 12, 2013.Mothers/newborn pairs at governmental hospitals of Tigray, Northern, Ethiopia and study units were mothers and their respective newborn found during the data collection in central zone of Tigray.All mothers that gave birth in the hospitals of central zone were included and mothers suffering from severe medical or surgical condition, twin delivery, mothers with unknown last menstrual period (LMP), and still birth, at the time of enrollment were excluded from the study.The required sample size was determined using single-population proportion with the following assumption: 22.5 % of prevalence of LBW in Ethiopia , 95 % ofA consecutive sampling technique was employed among mother-newborn pairs in the study area. For the qualitative aspect of the study, members of the FGD were selected purposively.The tool was designed to have four part that include socio-demographic characteristics , obstetric health  anthropometric measurements , socio-cultural patterns of feeding, .Quantitative: The data were collected using a structured pre-tested interviewer guided questionnaire which was prepared by reviewing similar literatures. Six data collectors who were midwives  that can speak the local language (Tigrigna Language), were recruited and two supervisors were selected from each woreda Health Office according to their research experiences.Qualitative: In order to explore the socio-cultural pattern of the community a total of three focus group discussions (FGD) which consists of 7-8 individuals in each group , was conducted using semi-structured, open-ended questionnaires in order to provide more insight in to the culture of feeding of pregnant mothers in the study area. The members of each FGD were selected purposively by the supervisors and the principal investigator and moderated by principal investigator with the assistance of trained note taker and tape recorder.To assure the quality of the data properly designed data collection instrument and training of data collectors were done. The enumerators and the supervisor were given training for two days on procedures, techniques and ways of collecting the data including calculating gestational age, measuring weight, height and MUAC. The collected data were reviewed and checked for completeness by principal investigator & supervisors each day. The questionnaire was initially prepared in English and then translated in to Tigrigna. The Tigrigna version was again translated back to English to check for any inconsistencies or distortions in the meaning of words & concepts. The questionnaire was pre tested prior to the actual data collection on 15 respondents that were not included in the main survey. The babies were weighed on beam balance up to 20 g accuracy within 2 hrs of delivery and all mothers were interviewed and examined within 6 hrs of delivery. The measurements were made on the participants wearing a minimum amount of clothing. The weights of pregnant women were recorded at the early first trimester during their first visit and continued in every visit by using a beam balance with an accuracy of 100 g. A standard WHO Mid upper arm circumference (MUAC) measuring tape was used to measure maternal mid upper arm circumference. The weight gain during pregnancy was estimated by subtracting the early first trimester weight from the last measured weight before delivery. Height was measured in cm using calibrated measuring steel attached to the beam balance. The pregnant women were asked to maintain an upright and erect posture with her feet together a horizontal headpiece was lowered onto the women’s head. Chronic medical illness has been operationalized as having any of the following illnesses: hypertension, diabetes mellitus, congestive heart failure, HIV during the course of current pregnancy.Formal letter of permission was obtained from Bahir Dar University ethical committee and Tigray Regional health bureau. The respondents were informed about the objective and purpose of the study and verbal consent was obtained from each respondent during data collection.p < 0.05 identified as independent predictors of LBW. The Hosmer-Lemeshow goodness of fit test provides an evidence for model fit with the predictor (p = 0.415). Multicollinearity effect has been checked in the multivariate model and all the variables were having a standard error <2.0. In regard to qualitative section of this study, the tape-recorded and the notes taken during Focus group discussion (FGD) were transcribed and then translated from Tigrigna to English in verbatim way. After the interviews listened for many times, the transcripts were reduced, coded and categorized in to themes, and finally triangulated with the quantitative results.Data were entered and analyzed using SPSS version 16.0 computer software package. Bivariate analysis was done with 95 % confidence interval to infer association, controlling the effect of confounders using multivariate logistic regression model. Variable which were found statistically significant at The study included 308 mothers/newborn pairs who delivered in governmental hospitals of central zone of Tigray, Northern Ethiopia; having a response rate of 100 %. The mean age of the study participants was 26.90 years (SD ± 5.86). Out of the respondents majority 254 (82.5 %) mothers were between 18-34 years of age. Two hundred ninety eight (96.8 %) of the respondents were married, 85 (27.6 %) mothers are unable to read and write and less than ten percent 24 (7.8 %) mothers did complete college and above. Related with the religion of respondents 295 (96.1 %) were Orthodox Christians (Table One hundred seventy nine (58.1 %) of the mothers had history of contraceptives use. The type of pregnancy that the mothers had, wanted and planed accounts for 274 (89 %), the unwanted and unplanned category accounts 16 (5.2 %). Concerning to inter-pregnancy interval, 268 (87 %) were delivered more than two years ahead of the index pregnancy. Almost all participants 303 (99 %) had history of antenatal care (ANC) follow up, of whom 215 (69 %) had 2-4 follow up and 57 (18.5 %) had greater than four visits during the current pregnancy. A significant number of mothers (92.5 %) have received dietary counseling during the ANC follow up (Table With regard to the birth weight of the newborns 263 (85.4 %) were above or equals to 2500 gs and the weight of children less than 2500 gs were 45 (14.6 %). The mean and standard deviations of the birth weights were 3094.9 ± 587.6 grams. Among the total respondents, 113 (36.7 %) had less than 50 kg of weight ). The risk of having LBW baby was more than two folds higher in mothers who had a body weight less than 50 kg when compared to mothers having body weight > = 50 kg ).Gestational age of the fetus on the risk of having low birth weight babies, the odds of being LBW in babies born before gestational age of 37 weeks was 18 times higher when compared to babies born at gestational age of 37 weeks and more ).Of the maternal obstetric factors the presence of any chronic medical illnesses during current pregnancy was assessed and it was found to be associated significantly with LBW. The odds of being LBW in babies born from mothers with history of chronic medical illnesses during their current pregnancy were found to have greater than five times chance of delivering LBW baby when compared with mothers with no history of chronic medical illnesses )  in the FGD were from rural and 3 (14 %) of the participants were Muslim followers, and the rest 18 (86 %) were Christian and the urban dwellers account for 14 (66 %) their ages ranged from 19-45 yrs.Three identified central themes under which the rest were included: Culturally prohibited foods and reasons of prohibition during pregnancy, feeding preferences and culturally recommended foods for pregnant mothers and fasting beliefs and practices during pregnancy and child birth.Food items like that of meat, fat, and butter are not encouraged for a pregnant mothers to eat frequently, because these food types leads the fetus to grow larger beyond the birth canal could tolerate and lead to severe complications during child birth” 33 yr old mother multi-para.“Majority of respondents described that the presence culturally prohibited food items and their practices have the tendency to affect their feeding patterns during the course of pregnancy. It is considered as refusals if they are not carried out as prescribed by their ancestors. This was supported by many of the respondent when they recited their practice and tradition of feeding.in addition to animal products honey shouldn’t be eaten during pregnancy because it leads to a pain full false labor that persists longer and it is also the main cause of constipation during the course of pregnancy.” 39 years old multi-para mother“…Another discussant added on this position as follows:“I was afraid of eating eggs, meat, and much cow’s milk while pregnant and I used to replace them with vegetables and some cereals products, this is because my parents advise on my feeding sequence to avoid the unnecessary growth of the fetus in my womb…” A 21 yrs old primi motherSimilarly an FGD participant also disclosed her fear as follows:“I used to prefer eating Injera (Ethiopian staple food), bread and vegetables, infrequently milk and animal products while I was pregnant, but soon shifted to porridges and frequent feeding of animal products after birth because I was told that animal products are not good during pregnancy to consume frequently” A 32 years old multi-para“…food items that are considered preferable based on advice of elders during pregnancy generally are all kinds of cereals their products like wheat flour and vegetables especially those that are eaten cooked”.A 29 years old woman claimed: “Frequent consumption of linseed in the late weeks of pregnancy is helpful in softening and lubricating the body of expectant mother, there by facilitate the course of child birth”A 42 years old and mother of 5 children added On the issue of food types which were considered safe and right for a pregnant woman during the course of pregnancy and child birth were almost supported by the study participants.“We have strong social ties in every aspect of life and it is difficult to ignore the advice of our elder family members & neighbors regarding the diet during pregnancy, we still obey their experiences since it could have truth in some instances and I sometimes strictly follow it despite the advice of health professionals and I always felt frightened to take much animal products” A 26 years old mother of two childrenOn the other hand respondents were seen to face difficulties on which food stuffs to consume during pregnancy regarding the sources of information at hand.Other discussants said the traditionally recommended foods were more accepted in the community many respondents listed them among the local foods to be similar as above. Financial concerns were common among participants; especially those who were unemployed that explain the preference of food depends on their income.“I was not fasting all the fasting hours during the course of my pregnancy but I never took non-fasting foods like meat, eggs and milk during the fasting time because I do not need to breach the rules of my religion and isolate myself from my family for this reason…”The respondents view regarding fasting during pregnancy was also incorporated in this study, there are few contradictions among the discussants on postponement of fasting after delivery. A 43 years old multi-para said Older parents and religious rules will never accept you to eat non-fasting foods whatever your pregnancy status rather they strongly advocate to fasting and have strong link with church, you did not obey this it is considered as a sinful act…”Women participating in the FGD frequently relied on parents, relatives and religious rules for support during pregnancy. Participants were asked for their perception what if they did not fast. “If someone disobeys the religious rules(if a woman is not fasting) either the mother will face problems during child birth or the child will be born with ill health that’s why I prefer to stick with it because I do not want to have unhealthy baby”.Another discussant added similar outlook “…I will never ask my religious father to such a permission (to having non-fasting foods) while pregnant because such permissions are allowed for conditions beyond your capability and for seriously ill individuals”.The issue of fasting among Christian followers is a bit different, that the majority of the discussants did not accept to taking non-fasting foods during pregnancy. A 41 years old woman claimed “…Generally, healthy and varied diet is important during pregnancy and the diet must provide sufficient energy and nutrients to meet the maternal daily requirements & the growing fetus. Pregnant women should try to consume plenty of iron- and folate-rich foods, and Vit.D throughout pregnancy, the important fatty acids and amino acids are crucial for fetal development of the brain, nervous system and retina  that fouIn this study an attempt has made to determine the prevalence and associated factors of low birth weight in the study area. Results of this study revealed that maternal weight, gestational age, residence, and presence of chronic medical illness were found to be significant predictors for low birth weight. The prevalence of low birth weight was found to be 14.6 %, which is similar with the LBW levels of sub-Saharan Africa countries , 7. ThisThe place of residence of the mothers was independently associated with the occurrence of low birth weight. Mothers residing in rural area were greater than 4 times more likely to have LBW babies when compared to those mothers who live in urban. This is consistent with the study done in Jimma zone and Tanzania , 12 thisThe qualitative part of this study design depicted that the culture of preference of nutritionally poor food items during pregnancy; it was profound and largely performed based on their family, parents and religious leaders despite medical advice. This predisposes mothers to miss timing nutritious food items and malnutrition during conception. The condition of malnutrition is also supported by the quantitative results of this study that showed the presence of maternal malnutrition as recognized on the anthropometric measurements that larger numbers of mothers were unable to achieve the average MUAC of pregnant women and weight during pregnancy.The use of qualitative study design to explore the effects of socio-cultural variables in this study.The involvement of midwives during anthropometric measurements during the survey and medical records were cross checked to confirm important variables such as patients’ hypertensive status, obstetric history, and antenatal history.Inability to include mothers who deliver at home and the presence of selection bias.A recall bias may be introduced during data collection time as some of the variables need a recall to situations happened few weeks/months back to the actual data collection time.This study depicted that the prevalence of LBW was found to be higher, pertaining the maternal factors associated with LBW, it has concluded LBW was found to be affected by rural place of residence, presence of any chronic medical illnesses, preterm birth  and maternal weight <50 kg. The qualitative part of this study found a strong influence of the socio-cultural beliefs in the nutritional intake of pregnant women. It particularly suggested that the presence of prejudice on animal products for fear of complications related to large baby during child birth. Preference nutritionally poor food items and miss timing of nutritious foods during pregnancy and child birth was also prominent accentuating the occurrence of low birth weight.Based on the findings of this study the following recommendations are forwarded:Attendants of ANC should receive disease specific counseling by skilled health personnel with emphasis given to mothers with chronic medical illnesses. Policy makers and health planers should optimize programs of community based nutritional promotion programs giving due attention to rural segment of the community. The zonal and woreda health offices should work on the adequacy of nutritional counseling given to expectant mothers with due emphasis given to mothers lower than 50 kg in weight. The tradition of feeding of pregnant mothers was determined by paramount influence of religious leaders & the community as a whole therefore, there is a need to intensively discussions on the issue of prohibited foods with regional health bureau to averting this problem. Community based further studies are also needed to identify the effects of seasonal variations of nutrition on the effects of birth outcome.


We found OH-PAHs were inversely associated with brain-derived neurotrophic factor (BDNF) (p < 0.05), and interquartile range (IQR) increases in OH-PAHs were associated with >16% BDNF decreases. Additionally, OH-PAHs were positively associated with activated leukocyte cell adhesion molecule (ALCAM) and C-reactive protein (CRP) (p < 0.05), and IQR increases in OH-PAHs were associated with >20% increases in CRP. We also found significant associations between these cytokines and HRV (p < 0.05), and IQR increases in BDNF and CRP were associated with >8% decreases in HRV. Our results indicated PAH exposure was associated with plasma cytokines, and higher cytokines were associated with decreased HRV, but additional human and potential mechanistic studies are needed.Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤−2, and  PM2.5 is a complex mixture and has been reported to be associated with increased risk of cardiovascular morbidity and/or mortality14The increase in fossil fuel-based energy production has led to massive amounts of fine particulate matter 6791111315Most existing epidemiological studies just have assessed associations between inflammatory markers and particulate air pollution as a whole mixture instead of specific constituents or internal exposure. In addition, some studies assessed these associations with small sample sizes1218p > 0.05). The distribution of these characteristics, urinary OH-PAHs, plasma cytokines, and HRV indices of 489 subjects in the validated stage were showed in As shown in q-value <5%] and 15 were lower  in the exposed samples  and selected 4 marked cytokines for validation from these 19 differentially expressed cytokines: brain-derived neurotrophic factor (BDNF), activated leukocyte cell adhesion molecule (ALCAM), CRP, and macrophage stimulating protein (MSP)  . Of thesin (MSP) .p ≤ 0.030). 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxyfluorene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and the sum of OH-PAHs (ΣOH-PAHs) were positively associated with the concentration of ALCAM . Most of the PAH metabolites, except for 9-hydroxyfluorene and 4-hydroxyphenanthrene, were positively associated with the CRP . Notably, urinary 1-hydroxypyrene was significantly associated with decreased BDNF, as well as increased ALCAM and CRP . We also observed significant associations of OH-PAHs (without creatinine-standardized) with BDNF, ALCAM, and CRP, respectively . Whereas CRP concentration was 51.03% higher  per IQR increase in 1-hydroxypyrene, 28.81% higher  per IQR increase in 1-hydroxynaphthalene (1.43 μg/mmol creatinine), 49.81% higher  per IQR increase in 2-hydroxynaphthalene (1.50 μg/mmol creatinine), 20.36% higher  per IQR increase in 2-hydroxyfluorene (0.69 μg/mmol creatinine), 25.50% higher  per IQR increase in 1-hydroxyphenanthrene (1.01 μg/mmol creatinine), 39.81% higher  per IQR increase in 2-hydroxyphenanthrene (0.30 μg/mmol creatinine), 23.80% higher  per IQR increase in 3-hydroxyphenanthrene (0.36 μg/mmol creatinine), and 42.85% higher  per IQR increase in ΣOH-PAHs (8.15 μg/mmol creatinine)  .p < 0.042); ALCAM was associated with lower HF ; and CRP was associated with lower standard deviation of all normal to normal NN intervals (SDNN), r-MSSD, low-frequency  power, and total power (TP) . When we further adjusted for the other 3 cytokines, the same trend of difference was observed (p = 0.052) and 21.29% , respectively, in association with an IQR increase in BDNF (8.00 ng/mL). And one IQR increment in CRP (1.74 ng/mL) was associated with decreases of 11.00%  in SDNN, decreases of 8.09%  in r-MSSD, decreases of 22.67%  in LF, decreases of 22.98%  in HF, and decreases of 16.54%  in TP, respectively  increase in PM2.5 exposure2.5 (13.6 μg/m3) was associated with decrease of 24.9% in SDNN in subjects in the upper 20th percentile of CRP. Significantly stronger effects of PM2.5 exposure on HRV was observed among the subjects with elevated CRP levels, even at ambient exposure levelsAdditionally, we found the positive associations between CRP and OH-PAHs and the associations of increased CRP with decreased HRV, suggesting that individuals with systemic inflammation are more susceptible to adverse effects of PAHs on the cardiac autonomic function. Evidence has showed people exposed to high levels of ambient air PM may increase CRP levelsp-values sometimes is unreasonable for some data, there are two concerns with this analysis: p-value’s under the null hypothesis is satisfied with (1) independent and (2) following uniform  distribution. And Bonferroni correction is controversial, in part because the choice of a denominator is arbitrary (given that the set of hypotheses that should be considered is not obvious). Besides that, statistically significant correlations were not observed between OH-PAHs and between each metabolite and the sum of all OH-PAHs. Meanwhile, we also cannot eliminate the possibility that the findings from the present study are by reason of chance or bias.Our study has several strengths. We have examined the associations of PAH exposure with cytokine changes and of these PAH-related cytokines with HRV in a relatively large sample size. The detection of the plasma cytokines was done in one key laboratory, and blinded duplicate samples were examined for quality assurance. In addition, we employed 10 urinary OH-PAHs as substitution for environmental PAHs exposure. Moreover, existing results from previous studies on the associations of circulating BDNF with cardiovascular events have not been consistent; our findings provide further evidence and clues to indicate the role of BDNF in the process of cardiovascular events. However, there are several limitations that should be noted when interpreting our results. First, our study is a cross-sectional study in which we measured PAH metabolites, cytokine levels, and HRV indices at the same time point, and it is not possible to determine whether differences in cytokines expression preceded or followed PAH exposures or cardiac autonomic dysfunction. Second, our sample is primarily male subjects and middle-aged which may limit generalizability of study findings. Third, three PAH-associated cytokines and other undetected cytokines in the discovery stage should be further validated in different populations with different PAH exposure levels. Fourth, we did not perform multiplicity adjustment in our study, considering False discovery rate (FDR) adjusted In summary, our study has identified three PAH-associated cytokines and found these cytokines were associated with a marker of cardiac autonomic dysfunction, suggesting that cytokines may be linked to cardiac autonomic dysfunction and may also increase vulnerability to the autonomic effects of PAHs exposure. However, further confirmatory studies and mechanistic researches are needed.We selected 497 participants from 1628 coke-oven workers who were employed at the coke plant of a steel mill in Wuhan  for at least 1 yearCytokine selection and validation” in “Materials and Methods”), and measured their concentrations in the remaining 489 workers by enzyme-linked immunosorbent assays (ELISA). For the cytokines that were significantly associated with at least one PAH metabolite, we further evaluated their associations with HRV indices. This study was reviewed and approved by the Medical Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. The methods were performed in accordance with the approved guidelines and regulations. The patients provided written informed consent before obtaining their biological materials.The present study was divided into two stages: discovery and validation stage. As ΣOH-PAHs had the highest correlation coefficients with 10 individual urinary OH-PAHs , we usedWe used gas chromatography-mass spectrometry to determine the concentrations of 12 urinary OH-PAHs: 10 were non-carcinogenic metabolites , and 2 were carcinogenic metabolites (6-hydroxychrysene and 3-hydroxybenzo[a]pyrene) which were always below the limits of quantification and were excluded from further analyses6www.raybiotech.com) in 8 exposed and 16 control plasma samples individually according to the manufacturer’s instructions. This quantitative array platform is a combination of seven forty-cytokine Quantibody arrays and uses the multiplexed sandwich ELISA-based technology. Briefly, multiple cytokines specific capture antibodies were first bound to glass surfaces. After incubation with the plasma samples, the target cytokines were trapped on the solid surface. Then we added biotin-labeled detection antibodies specific for different cytokines, which can recognize different isotope of the target cytokine.In the discovery stage, we determined the quantitative concentrations of a total of 280 cytokines  with Humq < 5.00%) between exposed and control group; 3) with signal values higher than 500 in each individuals; 4) were found to be involved in inflammation processes and/or be related to PM/PAH-mediated cardiovascular risk based on an extensive literature review. Four cytokines met these criteria: BDNF, ALCAM, CRP, and MSP. The concentrations of these four cytokines were measured by ELISA method in 489 workers in the validation stage. The concentrations of BDNF and CRP were measured using commercially available ELISA kits  according to the manufacturer’s instructions, and the detection limits for BDNF and CRP were 0.2 ng/mL and 0.01 ng/mL, respectively. The concentration of MSP was determined using Human MSP ELISA Kit ab100612 , the detection limit for MSP was 0.8 pg/mL. The concentration of ALCAM was examined using ELISA Duoset from R&D Systems (DY656): briefly, a 96-well microplate was coated with 100 μL per well of capture antibody at a concentration of 2 μg/mLWe selected cytokines based on the following criteria: 1) showed at least a 2-fold higher (FC ≥ 2) or lower (FC ≤ −2) expression in the exposed group compared with the control group; 2) with highly significant differences in expression  with a 1024 samples/second sampling rate for 10 minutest-test (for continuous variables) and chi-square test . The cytokine antibody array data were analyzed using Significance Analysis of Microarray (SAM) 3.00 algorithmhttp://statweb.stanford.edu/~tibs/SAM/index.html). SAM assigns a d-score to each cytokine on the basis of a multi-comparison analysis of expression changes and indicates significance by FC and q-value. In the validation stage, the associations between creatinine-adjusted urinary OH-PAHs concentrations and plasma cytokines, and between PAH-associated cytokines and HRV indices, were evaluated using multiple linear regression models with adjustment for age (continuous), gender (binary), BMI (continuous), smoking status (binary), pack-years of smoking (continuous), alcohol use status (binary), working years (continuous), and exercise (binary). Percent change in each cytokine and in each HRV index are presented with the increase of an IQR in PAH exposure levels and in cytokine concentrations, respectively, based on the following calculation formulas: [10(β × IQR) – 1] × 100%, with 95%CI {10[IQR × (β ± 1.96 × SE)] – 1} × 100%, where β and SE are the effect estimate and its standard error. We defined statistical significance as p value <0.05. Additionally, we have validated all these related linear regression models with linearity, no auto-correlation, no multicollinearity, normality on residuals, and homoscedasticity.We conducted data analysis using SPSS, version 18.0 . The levels of 10 creatinine-adjusted non-carcinogenic OH-PAHs, four plasma cytokines, and five HRV indices were natural logarithm (ln) transformed to improve normality and stabilize variance. In the discovery stage, the differences of general characteristics between control and exposed groups were analyzed using Student’s How to cite this article: Yang, B. et al. Exposure to Polycyclic Aromatic Hydrocarbons, Plasma Cytokines, and Heart Rate Variability. Sci. Rep.6, 19272; doi: 10.1038/srep19272 (2016).


There is some evidence linking sub-optimal prenatal development to an increased risk of disability pension (DP). Our aim was to investigate whether body size at birth was associated with transitioning into all-cause and cause-specific DP during the adult work career.10 682 people born in 1934–44 belonging to the Helsinki Birth Cohort Study had data on birth weight extracted from birth records, and on time, type and reason of retirement between 1971 and 2011 extracted from the Finnish Centre for Pensions.Altogether 21.3% transitioned into DP during the 40-year follow-up, mainly due to mental disorders, musculoskeletal disorders and cardiovascular disease. Average age of transitioning into DP was 51.3 (SD 8.4) for men and 52.2 (SD 7.6) for women. Cohort members who did not transition into DP retired 10 years later on average. Among men, higher birth weight was associated with a lower hazard of transitioning into DP, adjusted hazard ratio (HR) being 0.94 . For DP due to mental disorders the adjusted HR was 0.90, 95% CI 0.81, 0.99. A similar but non-significant trend was found for DP due to cardiovascular disease. Among women there were no associations between body size at birth and all-cause DP (p for interaction gender*birth weight on DP p = 0.007).Among men disability pension, particularly due to mental disorders, may have its origins in prenatal development. Given that those who retire due to mental health problems are relatively young, the loss to the workforce is substantial. Disability pension (DP), considered as a permanent exit from the workforce due to a medical cause, has been increasing in Europe over the past decades and it has significant economic implications at both the individual and societal level . In 2011Research on underlying causes of transitioning into DP has mostly focused on socioeconomic status in childhood and adulthood, related health conditions ,5 and onrd trimester led to babies being born asymmetrically small for gestational age (A-SGA), and these babies had increased risk of DP. Based on these earlier findings we hypothesized that smaller body size at birth was associated with a higher risk of subsequent disability pension among men and women. Using data from the Helsinki Birth Cohort Study the aim of the present study was to investigate if birth weight was associated with transitioning into all-cause and cause-specific disability pension during the adult work career and whether childhood and adulthood socioeconomic status explained the potential association.We have previously shown in the Helsinki Birth Cohort that small body size at birth, a consequence of an adverse prenatal environment and suboptimal growth, is associated with a higher risk of coronary heart disease , mental t-test p>0.143). The study was approved by the Ethics Committee of Epidemiology and Public Health of the Hospital District of Helsinki and Uusimaa and that of the National Public Health Institute, Helsinki. Written consent was not given by the cohort members, however, the data were anonymized prior to analysis.The Helsinki Birth Cohort Study comprises 13 345 individuals born in Helsinki, Finland at Helsinki University Central Hospital or Helsinki City Maternity Hospital between 1934 and 1944 and who had data on birth anthropometry extracted from birth records . Of the th and 10th versions into the following groups: mental disorders (ICD 9 codes 290–319 and ICD 10 codes F00-F99), diseases of the musculoskeletal system (710–739 and M00-M99); cardiovascular diseases (CVD) (400–459 and I00-I99); diseases of the nervous system (320–359 and G00-G99); and all other diagnoses.All Finnish residents are covered by the pension system. Before reaching the statutory retirement age employees can apply for disability pension if, due to a medically confirmed illness, they are unable to continue working even after periods of rehabilitation, re-education or assistance . Using tBirth date, weight, length and birth order of the newborns were retrieved from the hospital birth records described in detail previously ,16,17. BBirth weight was standardized into a Z-score indicating the number of standard deviations by which an observation differs from the mean of the entire study cohort. To test for potential gender differences we first analyzed the interaction ‘gender*birth weight’ on DP in a Cox regression model and because the term was statistically significant (p = 0.007), subsequent analyses were stratified by gender. Nelson-Aalen cumulative hazards of retirement were calculated for the 40-year follow-up time in groups according to non-DP and DP due to mental disorders, musculoskeletal disorders, cardiovascular diseases and all other diagnoses.Using Cox proportional hazards models we estimated the hazards and their 95% confidence intervals for transitioning into DP during the 40-year follow-up for birth weight. Follow-up time was calculated as the number of days between date of birth and date of retirement. In these models non-disability pensioners were treated as censored cases while each disability pension category in turn was treated as an event. Separate analyses were conducted for the main disability pension diagnoses. The proportional hazards assumption was assessed using a test based on scaled Schoenfeld residuals to identify variables for which associations varied over time. Diagnostic investigations indicated that only the effect of birth weight on retirement due to mental disorders among women was not proportional over time. In the Cox models, after the crude model, we first adjusted for birth order and socioeconomic status in childhood and then for highest educational attainment and highest occupational class in adulthood. Cox models were stratified on year of birth to control for potential cohort effects. Modeling was performed with IBM SPSS version 22.0 except for the Nelson-Aalen Cumulative Hazard computation and Schoenfeld residual checks which were performed in the R statistical programming environment (version 3.0.3) using the survival-package (version 2.37–7).2 test p<0.001).Altogether 21.3% (23.5% men and 18.9% women) of the study members transitioned into DP during the 40-year follow-up period. The average age of transitioning into DP was 51.3 years (SD 8.4) for men and 52.2 years (SD 7.6) for women whereas those who transitioned into non-disability pension worked on average 10 years longer and retired at an average age of 61 years see . Birth wThe two leading causes of DP were mental disorders  and musculoskeletal disorders  and the other main causes were CVD and diseases of the nervous system. Nelson-Aalen Cumulative Hazards were calculated for non-DP and DP due to the main diagnoses  for the 40-year follow-up period . The cumCox regression models indicated that higher birth weight among men was associated with a lower hazard of all-cause DP in the follow-up, HR 0.93 (95% CI 0.88–0.98 for 1 SD increase in birth weight) . The ass3) instead of birth weight in the Cox regression models and found the associations to be similar. Then, we further adjusted the models for gestational age, mother’s BMI and age, but they did not attenuate the associations between birth weight and DP. We added the quadratic and cubic terms of birth weight in the Cox regression models but because these terms were not significant we did not include them in the final models. Finally, we included the 1800 persons in the HBCS who had died or migrated and did not retire in the Cox regression models as censored cases, but this did not change the results.We conducted sensitivity analyses by first using ponderal index Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


The high frequency of alterations of the stomatognathic system associated with premature birth may suggest that prematurity is an important risk factor in the development of this system. Prematurity has an incidence between 6-11% of births and is associated with factors such as genetic, maternal conditions  and antenatal care. In addition, undesirable situations, such as changes in enamel and the development of the skeletal structure, also appears to be associated with prematurity. This study aimed to look for changes in the stomatognathic system at five years of age associated with premature birth.We estimated the prevalence of developmental disorders of the stomatognathic system in the primary dentition of preschool children at five years of age. Changes in preterm infants (n = 32) compared with term born (n = 381) were evaluated . Clinical examinations and questionnaire with sociodemographic and health of mothers and children information. Gestational age, birth weight, head circumference, Apgar score and mechanical ventilation, were collected from the medical records to birth records. The explanatory variable was preterm .Results: Prevalence of 7.7% of preterm infants was found. Of these, 40.6% had atresic palate, 56.2% malocclusion and 21.8% enamel hypoplasia. Forty (9.6%) children were not breastfed at the breast, and 26 (65.0%) had some type of malocclusion, showing association between not breastfeeding with an abnormal development of the stomatognathic system. The group of preterm infants showed five times more changes in head circumference and three times more mechanical ventilation use at birth. Change in head circumference at birth and mechanical ventilation has a significant association between groups of preterm and term infants.Mechanical ventilation at birth directly contributed to an increased risk of developmental disorders of the stomatognathic system in preterm infants, especially dental hypoplasia. Non-breastfed children had a higher risk of developing malocclusion. Alterations in head circumference were related effective on dental malocclusion. The results suggest that changes in the stomatognathic system are influenced by premature birth and points to the imperative need of using methods of preventive. Premature birth, a major public health challenge in Brazil, occurs in 6-11% of births and is associated with the large majority of infant and childhood deaths. Premature delivery may result in high financial costs and potential social and economic problems for the affected families [The identification of factors associated with premature birth and the reduction of its harmful consequences is challenging due to the complexity and multi-causal relationships of the variables involved. Associations with genetic factors, obstetric care, nutritional status, infections, toxic exposure, antenatal care, demographic, psychosocial and environmental problems have been reported ,3. HowevPrevious population-based studies have not adhered to any specific standards; therefore it is difficult to compare results between studies. There is ample evidence that certain chronic diseases and unfavorable characteristics may originate during fetal life, e.g., cardiovascular disease and diabetes . HoweverEpidemiological studies on oral health in early childhood describe the changes in the stomatognathic system and help to establish preventive and educational programs that may control the symptoms and reduce the costs incurred . This stth to July 15th 2005. For a detailed methodology describing aspects of delivery and childbirth see our previous study [This research is characterized by being a living longitudinal study of a birth cohort, to estimate the prevalence of developmental disorders of the stomatognathic system in the deciduous dentition of 413 five-year-old pre-school children from Aracaju, Sergipe. These children were from a cohort of births registered in the four maternity hospitals in the metropolitan area of Aracaju (ESPHA) in the period from March 8us study . The finInitially, individuals were identified during visits to schools in the city of Aracaju, health units and Reference Centers. Specially trained staff interviewed mothers or guardians and completed survey forms containing the child’s overall development and detailing their socio-demographic, socio-economic, nutritional status and any behavioral, speech, hearing or associated diseases. Data collection was blind with regard to the children’s birth condition. The resulting data was divided according to gestational age: in preterm infants up to 36 weeks and six days (n = 32) and term infants, 37 completed weeks or more (n = 381). A paragraph that explicitly says the sample limitations in this research was added in the method. The limitation of sample numbers was mainly due to absence of children on their schools, with frequent medical certificates caused by common diseases. The professors state that these families go through long periods of unemployment or frequent employment changes of one or of all family members. To work around this reality, families seek amendment of the residential lease and the number of fixed or mobile phone and a plan of lower cost, which hampers its location. Another strategy used during the school year is the change of city and state, and often the child goes to live with relatives in other municipalities. This situation causes weakness of family bonding and of the school links, at least transiently. The economic reality of the family, possibly generates absenteeism and dropout of students in various phases of the school year, which possibly hinder the process of teaching and learning. This may also be a reason for the small proportion of the original cohort children that was found.The final number of children evaluated in this study was significant and became very relevant especially when compared with previous research, and we have larger sample than before ,8. The eThe tests for the evaluation of the stomatognathic system were conducted using a collection tool designed especially for this survey. Eligible participants were examined between March 2010 and January 2011. These children were assessed for palatal development by measuring intercanine distance, changes of enamel, malocclusion and abnormal number of dental units. Prior calibration was performed between the chief examiner and the examiner’s assistant, in case there was any need for the replacement of the dentist. The validation of the calibration was measured using a Kappa test for standardization of tests resulting in a weighted kappa coefficient value of 0.659.The stomatognathic system was examined using the following instruments: tongue depressors, dental mirror (sterilized), spotlight and front chair for onsite examination. The examiner wore standard personal protective equipment . Evaluation followed a predetermined sequence: palatal evaluation was performed by clinical inspection ,with the examiner making notes about this evaluation sorting the palate between normal or atresic, in sequence, the intercanine distance was measured from the cusp tip, or the center facet of wear, of the canine on one side of the arch to the opposite canine with the help of a digital caliper as established by Moorees in 1966 [We evaluated the dentofacial alterations of occlusion in deciduous dentition using the standard proposed in the Project SB Brazil 2003 [The number of dentofacial changes was established as: 0 , 1 (anadontia) no tooth, no evidence of tooth yet to break or early loss; 2 , 3 (Twin pregnancy) used for clinical definition of a merger or twinning dental in the absence of radiographic examination complementary for diagnosis.Explanatory variables, such as the child’s head circumference at birth, the one-minute Apgar score and gestational age, were collected at the moment of birth through the completion of standardized questionnaires. The data for the mother and the newborn of the 2005 cohort were retrieved from the databases.Profile frequencies and socio-demographic variables were estimated and calculations of prevalence were carried out for each explanatory variable. Associations of categorical variables were assessed using the chi-squared test between the study group and the control groups. Multiple logistic regression was performed considering an explanatory variable, adjusted to a model for the response variable taking into account more than one explanatory variable. . The right to leave this study at any time, access to the results and complete confidentiality were all guaranteed. This study fulfills all ethical principles required and was approved by the Ethics Committee of the Universidade Federal de Sergipe (Case 138/2004).During the study period, we performed 413 examinations of the stomatognathic system. The two groups had similar distributions for birth weight, type of birth and gender. We evaluated 32 premature children (7.7%) and 381 at term  children had an abnormal head circumference. Premature children were more likely to have a head circumference outside of normal parameters  and required more mechanical ventilation , as shown in Table There was no statistically significant difference with regard to malocclusion between the two groups Table .Table 3The averege intercanine distance in the group of preterm infants was 33.59 mm, while in term infants it was 35.49 mm (p = 0.004) as shown in Figure Anomalies in the development of stomatognathic system are associated with premature birth. Unfavorable conditions of preterm birth seem to contribute directly to the occurrence of atresia of the palate and malocclusion.We found that 75% of preterm infants was bottlefed at an early age, which could be a contributing factor to the high prevalence of malocclusion. Our results showed that 56.2% of this population demonstrated crossbite and 40.6% had palate atresia.We could not confirm any significant changes in enamel in this population. However, other studies -10 have The prevalence of prematurity (7.7%) in the studied population is consistent with previous findings , which rThe stomatognathic system comprises static and dynamic oral structures that play important roles in neurovegetative functions , speech and facial expressions. Separately or in combination, anomalies resulting from prematurity may unfavorably affect the facial aesthetics ,13.Premature children suckling, which is usually not very vigorous, favors the introduction of nutritive and non-nutritive habits such as bottles, pacifiers and finger causing alterations on the morphology of hard palate, modifications on dental positioning and on tongue movement -16. In tIn this study, we report an association between pregnancy outcome and growth of the palate. We measured the intercanine distance, corroborating the previous report by Palmer , which rThe importance of breast feeding for harmonious growth of the masticatory system is directly related to the proper exercise of the facial muscles in the act of sucking, stimulating muscle tone and development of the temporomandibular joint, providing enough space for the tooth eruption . Our resLearning and refining the techniques required for sucking, swallowing, breathing properly with sucking and hatching and ingesting the correct volume of milk not only increases with gestational age, but also with food experience. The latter occurs late or inefficiently in preterm children, increasing the chance of developmental muscle and skeletal orofacial disorders due to low/ lack of stimulation -20.Structural alterations of skeletal development may also be related to local trauma arising from laryngoscopy or tracheal intubation, which is more common in premature infants ,21,22. AThere was a significant association between the head circumference measurement and mechanical ventilation at birth between the two groups, therefore we identified these as risk factors related to premature birth. Epidemiological surveys are useful for highlighting health problems in a population. Through studies like this, it is possible to plan, propose and develop effective treatments for the problems identified here. Therefore, this survey is useful for helping organizations to define health actions that may be required.The early introduction of artificial feeding, parafunctional habits and oro-tracheal intubation described in this study indeed occur very frequently. Regrettably, public health policies for preterm birth and its consequences are still far from the desired level and more actions are required to encourage improvements and an enhanced understanding of the disease/health process.The rates of change of tooth enamel are higher in preterm infants. Changes in head circumference, corrected gestational age, have effective relationship on dental malocclusion. Unfavorable conditions such as mechanical ventilation at birth directly contribute to an increased risk of developmental disorders of the stomatognathic system, the main change being found Enamel hypoplasia. Thus, it is necessary to develop preventive treatments for premature infants, which allow for the proper growth and development of the stomatognathic system. A first step would be to encourage breastfeeding, not only by the neonatologist but also by all health care staff, and to provide more guidance and advice to mothers and families during their child’s recovery process. This would minimize the chances of adverse consequences in premature births.


There was no significant change in median PI values in the following 8 min.Perfusion index is a continuous parameter provided by pulse oximetry and might be useful for evaluating hemodynamic changes at birth and identifying transitional problems. The objective was to describe perfusion index values in term infants immediately after birth. Perfusion index of 71 healthy term born infants were recorded during the first 10 min after birth, using a pulse oximetry sensor placed preductally. A Wilcoxon signed-rank test was used to compare between time points. No significant trend in perfusion index could be observed in term-delivered infants. There was a significant difference between 2 and 3 min (2.4 (1.6–5.0) vs. 2.3 (1.6–3.7), Conclusion: Perfusion index does not change significantly during transition at birth in healthy term infants born by normal vaginal delivery or cesarean section. Large variation in perfusion index causes monitoring this parameter to have limited value. PI is calculated as the ratio of the pulsatile signal  indexed against the non-pulsatile signal  and is a non-invasive indicator for peripheral perfusion [In recent years, pulse oximetry (PO) has been recognized as an easily applicable, non-invasive monitoring tool and is now routinely used in the delivery room to monitor transition at birth , 22, 24.at birth , 26, andat birth , 20, 31.erfusion . PI has erfusion  and voluerfusion , 12.2 and HR are used for clinical evaluation, but these parameters do not reflect the complete hemodynamic status of the infant at birth [During neonatal transition, significant respiratory and hemodynamic changes occur, influencing cardiac output as well as systemic and peripheral perfusion , 19, 25.at birth . Tissue at birth . Continuat birth  and the at birth , 13, PI We analyzed PO recordings of healthy term infants born via uncomplicated vaginal delivery or elective cesarean section who did not need medical support. The study was approved by the LUMC institutional review board and the parents were approached before birth for informed consent. Recordings of term infants born between February 2012 and March 2013 were reviewed retrospectively. Gestational age was determined by performing an antenatal ultrasound, which is standard of care in the Netherlands. Recordings were included if PI measurements were obtained shortly after birth and time of birth was indicated. Recordings were excluded if infants received respiratory support.2 were recorded by one member of the research team. During each delivery, a pediatric resident, a neonatal IC nurse, and one researcher were present. The researcher (JV) put the PO sensor on. The PO sensor  was always placed on the ulnar aspect of the right wrist providing preductal arterial values [2 were recorded at maximum sensitivity every 2 s from 2 min after birth until 10 min after birth or earlier if the infant was placed in the transport incubator. The recorded values were collected using the Spectra Physiological Recording Program  and stored on a laptop. Data were averaged for each infant at each 60 s interval, comprising of the data points of 10 s of data before and after each 60 s interval. Data were considered valid for analysis if PI, HR, and SpO2 were simultaneously present at a time point and the plethysmography pulse wave was confirmed to be artifact free. Limits of PI values identified to be unvalid were ≤0.02 and ≥20 and simultaneous absence of HR and SpO2 values [Directly after birth, the infant was placed under a radiant warmer. PI, HR, and SpOl values  and connl values . PI, HR 2 values .p = 0.05/2 = 0.025). A (two-sided) p value of <0.05 was considered as statistically significant.Data were analyzed using SPSS 20.0 for Windows . All variables were tested for normality using the Kolmogorov-Smirnov test. Data were presented as mean (SD) or median (IQR), where appropriate. For non-normally distributed data, a Wilcoxon signed-rank test was used to compare PI between time points within groups. To account for multiple comparisons between the time points, tests were performed using the Bonferroni corrected level  gestational age of 40 (1) weeks and a birth weight of 3575 (482) grams were recorded and analyzed. Thirty-nine infants were born after cesarean section and 32 infants were born after vaginal delivery. Median (IQR) Apgar score was 9 (9–9) at 1 min and 10 (10–10) at 5 min. 97 % of data (5860 data points) of the PI measurements were of good quality and were included.2 simultaneously was 110 s (110–126 s). HR and SpO2 were within ranges described by Dawson et al. (Table p < 0.001). There was no significant change in median PI values in the following 8 min  taken to acquire PI, HR, and SpO s 110–12 s. HR an2 and HR, we observed that PI decreases significantly during between 2 and 4 min after birth, after which remains stable, and no trend could be observed. Currently, the only non-invasive monitoring used in the delivery room is the measurement of heart rate. This does not reflect the complete hemodynamic status of the infant at birth [This is the first study reporting the course of PI of healthy term infants during transition at birth. Significant physiological changes occur during transition and although this is reflected by changes in SpOat birth . PI coulHawkes et al. found a moderate correlation with HR and found no significant correlation for PI with blood pressure values, lactate levels, and gestational age. Furthermore, no trend was observed during the first 10 min of life .The observed PI is similar to a previous study by de Felice et al., reporting no differences in PI values measured at 0–1 min and 1–5 min after birth . This coWe measured a lower preductal PI at 5 min after birth than de Felice et al. measured postductally in healthy term infants (4.4 (2.1) vs. 2.0 (1.4–3.5)) . This diDe Felice et al. suggested PI values <1.24 as an accurate predictor for severity of illness . Althoug2, a continuous monitoring could give the caregiver more information than a single value. Although we reported values of healthy term infants, comparison with term infants with transitional problems is needed to determine whether the PI is a useful parameter for hemodynamic evaluation of transition and clinical decision making.The nature of this study was retrospective. We intended to provide PI values for healthy infants during the first minutes after birth and infants that needed medical support were excluded. Therefore, this did not influence our findings. A limitation of our study is the performance of the PO which could explain the wide range in PI observed during transition . WhetherIn conclusion, we reported PI measurements in healthy term infants during the first 10 min after birth. There was a small but significant decrease in PI during the first 4 min, after which PI remained equal and variability was high healthy term born infants.


Despite of higher pregnancy rate after frozen embryo transfer (FET) which is accepted by the majority of researches, the safety of this method and its effect on neonatal outcome is still under debate.The aim of this study was to evaluate pregnancy and neonatal outcome of FET compare to fresh cycles.In this study,1134 patients using fresh ET and 285 women underwent FET were investigated regarding live birth as primary outcome and gestational age, birth weight, gender, multiple status, ectopic pregnancy, still birth and pregnancy loss as secondary outcomes.Our results showed that there is no difference between FET and fresh cycles regarding live birth (65.6% vs. 70.4% respectively). Ectopic pregnancy, still birth and abortion were similar in both groups. The mean gestational age was significantly lower among singletons in FET group compared to fresh cycles (p=0.047). Prematurity was significantly elevated among singleton infants in FET group (19.6%) in comparison to neonates born after fresh ET (12.8%) (p=0.037).It seems that there is no major difference regarding perinatal outcome between fresh and frozen embryo transfer. Although, live birth is slightly increased in fresh cycles and prematurity was significantly increased among singleton infants in FET group. Introduction of embryo cryopreservation was a revolution in assisted reproductive technology (ART). Transfer of frozen embryos has been increasingly used during the past few decades, as it is a well-known part of ART nowadays. Frozen embryo transfer (FET) has several advantages and among them, the similar or even higher pregnancy and live birth rate compare to fresh cycles is of great importance . In addiFET also is a useful method for preserving extra good quality embryos in women with good response to ovarian stimulation, increasing elective single embryo transfer and avoiding multi-gestations as well as ovarian hyperstimulation syndrome. Regardless of cryopreservation technique improvements, safety aspects and its impact on the health of children born are uncertain. et al showed a higher prenatal mortality rate among singletons born after FET  , 11. In Study populationTo study the impact of FET on neonatal outcome, in a cohort study, 300 women using FET and 1150 women undergoing fresh embryo transfer were compared. Participants remained in the cohort until the livebirth occurred. The study was conducted at Yazd Madar Hospital over a 4-years period between December 2010 and December 2014. This study was approved by the Ethics Committee of Research and Clinical Center for Infertility, Yazd University of Medical Sciences.Data CollectionData were collected from the hospital records. In addition a telephone questionnaire consists of data on maternal and neonatal factors was administered by a trained nurse based on patients and their husbands’ information. Patient’s data included maternal age at birth, duration and causes of infertility. The primary outcome was live birth. The secondary outcome variables were perinatal data contains gestational age, birth weight, gender, twin status, stillbirth, ectopic pregnancy (EP) and spontaneous abortion.th centile for gestational age. LBW: <2500 gr at birth. Stillbirth: Fetal death more than 20 wks of gestational age. EP: Finding of extra uterine pregnancy by laparoscopy or ultrasound. Spontaneous abortion: Loss of pregnancy before 20 wks of gestation. The increased miscarriage rate in this survey is thought to be due to pregnancy loss calculation, according to chemical pregnancy in women with an initial positive β-hCG test.Outcomes were defined as followed: Preterm birth: <37 wks of gestational age at delivery. Small for gestational age (SGA): Birth weight less than 10Ovarian stimulation protocolTwo protocols were used for ovarian stimulation: GnRH agonist long protocol and GnRH antagonist protocol as described previously , 16.Embryo cryopreservation techniques and transfer protocolsAll embryos were morphologically evaluated on the second day after oocyte retrieval. Number of blastomeres and cytoplasmic fragmentation was assessed. Two embryos with good or excellent quality were transferred in fresh cycles, only in women over the age of 40 and regarding patients’ request, 3 embryos were transferred. All the extra embryos with less than 30% fragmentation were cryopreserved by vitrification method. During two step loading protocols, embryos were loaded with equilibration solution containing 7.5% dimethyl sulfoxide (DMSO) (Sigma-Aldrich) and 7.5% ethylene glycol (EG)  in Ham’s F-10 media supplemented with 20% patient serum for 5-15 min at room temperature. Once the primary shrinkage and recovery, embryos were aspirated and placed into the vitrification solution 15% EG, 15% DMSO and 0.5 M sucrose  in Ham’s F-10 medium supplemented with 20% patient serum for 50-60 sec at room temperature. The embryos then were loaded by a thin glass capillary tube into the cryotop and the samples were immediately submerged into liquid nitrogen for at least 2 months. For thawing, cryoprotectants were removed step by step using embryo thawing media  by insertion the Cryotop in thawing solution (1 M sucrose) for 50-60 sec and next into dilution solution (0.5 M sucrose) for 3 min, after that embryos placed in another dilution solution of 0.25 M sucrose for 3 min, all at room temperature. The thawed embryos were placed 4-5 times into washing solution (Ham’s F-10 +20% serum) before incubation. After embryo transferred to culture medium, they considered morphologically survived by 50% or more intact blastomeres and no injury to zonapllucida. Only intact or partly damaged embryos were transferred.Endometrial preparation was performed using oral Estradiol Valerat  at the dose of 6 mg per day from the second day of menstrual cycle until the endometrial thickness reached more than 8 mm, and then 100 mg progesterone in oil  was injected or Cyclogest 400 mg  was used daily. Estradiol and progesterone administered continuously until observation of fetal heart activity by ultrasound. Embryo transfer was done 3 days after the beginning of progesterone injection using a Labotect  or Cook catheter .Statistical analysist test. The Chi-square test was used to compare non-continues variables. Statistical significant was set at a p<0.05. Adverse or protective effects of FET on perinatal outcome versus fresh cycles are expressed as odds ratio.The Statistical Package for the Social Science version 20 for windows  was used for data analysis. Differences between normally distributed continuous variables were measured by Student’s 1150 women using fresh ET and 300 women undergoing FET were initially enrolled the study. Sixteen women in fresh and 15 women in FET group were excluded because of refusing to participate or loss to follow up. Patents basic characteristics were not significantly different .It is shown that FET cannot increase the chance of live birth (65.6% vs. 70.4% in fresh group) OR=0.80 (CI: 0.61-1.05) (p=0.120) . 79.1% oThe mean gestational age at the time of delivery was lower among singletons in FET group than fresh cycles (37.34±2.47 vs. 37.77±1.90 respectively) and the difference was statistically significant (p=0.047). Whereas, the mean gestational age of twin and triple pregnancies was significantly higher in FET group compared to fresh embryo transfer. There were no statistical differences in the mean live birth along with singleton and twin newborns between groups. Only triple pregnancies had a considerable higher birth weight in FET versus fresh cycles (p=0.028) . As it is presented in In this study, we compared perinatal outcomes after FET with fresh ET cycles. The main finding was that live birth slightly increased in fresh group without significant difference. As secondary outcomes, EP, spontaneous abortion and still birth did not differ between FET and fresh cycles. In our previous study, live birth regardless singletons or multiples was significantly lower in FET group . Howeveret al and Jun found no significant alteration in EP between FET and fresh cycles  between fresh cycle and FET group. In our previous survey only singleton pregnancies showed a significant higher sex ratio in FET group compare to fresh embryo transfer . Similarnception .In conclusion, according to our results, it seems that there is no major difference regarding perinatal outcome between fresh and frozen embryo transfer. Our data revealed that live birth did not differ significantly between FET and fresh cycles with a slight elevation in fresh group. The other outcomes including EP, spontaneous abortion , still birth and SGA were similar in both groups. Our findings showed that FET significantly increases the risk of prematurity and LBW in singleton pregnancies.