APOA5, hepatic lipase and PPARγ genes and investigated their association with birth weight and serial changes in BMI.Triglycerides is an independent risk factor for coronary artery disease (CAD) and is especially important in Indians because of high prevalence of hypertriglyceridemia in this population. Both genetic and environmental factors determine triglyceride levels. In a birth cohort from India, hypertriglyceridemia was found in 41% of men and 11% of women. Subjects who had high triglycerides had more rapid body mass index (BMI) or weight gain than rest of the cohort throughout infancy, childhood and adolescence. We analysed polymorphisms in APOA5 , PPARγ (Pro12Ala) and hepatic lipase (-514C > T) were studied by polymerase chain reaction (PCR) followed by restriction digestion in 1492 subjects from the New Delhi Birth Cohort (NDBC). We assessed whether these polymorphisms influence lipid and other variables and serial changes in BMI, both individually and together.Polymorphisms in APOA5 (-1131C) resulted in 23.6 mg/dl higher triglycerides as compared to normal allele (P < 0.001). Risk allele of HL (-514T) was associated with significantly higher HDL2 levels (P = 0.002). Except for the marginal association of PPARγ Pro12Ala variation with a lower conditional weight at 6 months, (P = 0.020) and POA5A S19W with a higher conditional BMI at 11 yrs of age (P = 0.030), none of the other associations between the gene polymorphisms and serial changes in body mass index from birth to young adulthood were significant.The risk allele of APOA5 was associated with raised serum triglycerides and that of HL with raised HDL2 levels. None of the polymorphisms had any significant relationship with birth weight or serial changes in anthropometry from birth to adulthood in this cohort.The promoter polymorphism in  There were 9169 pregnancies resulting in 8181 live births. Trained personnel recorded the weight and the length of the babies within 72 hrs of birth, at the ages of 3, 6, 9 and 12 months (±7 days) and at 6 months interval thereafter. There were many phases in this cohort study . More than 30% of the cohort was lost between the end of phase I and beginning phase 2, a time when unauthorized housing was demolished in South Delhi. In the current phase, between 1998-2002, 31.6% of the initial cohort could be located. 1526 subjects provided consent and participated. Close to 1/10th of these subjects had impaired glucose tolerance (10.8%), and 4.4% were diabetic. Another important finding was that 41% of men and 11% of women had hyper-triglyceridemia. Subjects who had high triglycerides had more rapid body mass index (BMI) or weight gain than rest of the cohort throughout infancy, childhood and adolescence [Interaction between genetic and environmental factors determines susceptibility of an individual to develop coronary artery disease. Triglyceride is an independent risk factor for coronary artery disease (CAD) and is especially important in Indians because of high prevalence of hypertriglyceridemia in this population. In a well-established birth cohort  of individuals born between the years 1969 to 1973 and followed up in many phases in terms of anthropometric measures and in 2002 for biochemical risk factors of diabetes and CVD, we have earlier demonstrated an inverse relation between thinness in infancy and the presence of impaired glucose tolerance or diabetes in 1492 young adults [APOA5 is an important determinant of triglyceride levels [APOA5 gene have been shown to be associated with raised triglyceride levels in different populations [PPAR-γ regulates a number of adipocyte genes involved in pathways of lipid metabolism. A "G" to "C" substitution in exon coding for PPAR-γ results in proline to alanine amino acid change (PPARγ Pro12Ala). The Ala isoform of PPAR-γ is less effective at targeting genes and is found to be significantly associated with dyslipidemia in obese [HL gene (C-514T) is associated with diminished lipase activity, dyslipidemia, and atherosclerosis [APOA5 gene polymorphisms: -1131T > C and S19W, PPARγ gene polymorphism- Pro12Ala and hepatic lipase C-514T polymorphism on lipid levels and also the relationship with serial changes in BMI from birth to adulthood in the NDBC.Triglyceride metabolism is both under genetic and environmental influences. It is likely that genes which influence triglyceride levels have different effects on people with different birth weight and or weight at infancy or childhood . APOA5 ie levels  and it'sulations . PPAR-γ in obese . Hepaticclerosis . We studThe study was carried out from blood samples of the NDBC subjects n = 1492) stored at -70°C which were collected during the period 1998 to 2002 (Details published elsewhere [492 storeAPOA5 -1131T > C polymorphism was genotyped by ARMS (Amplification Refractory Mutation System)-PCR method described by Chandak et al [PPAR-γ Pro12Ala polymorphism, mutagenically separated PCR was performed. A 230 bp product identifies the Pro allele and 250 bp product the Ala allele. To assay the C-514T HL polymorphism in the promoter region, a 299-bp fragment containing the restriction site was PCR-amplified. The amplified DNA was digested with Nla III generating two fragments of 229 bp and 70 bp in subjects with "T" allele. Positive and negative controls were included in all RFLP runs. For quality assurance of data generated, 10% samples were regenotyped at CCMB and a near 100% concordance was observed. This validates the data generated on all the samples and hence the association analyses conducted on the genotypic and allelic frequency is robustDNA was extracted by salting out method . APOA5 -All biochemical parameters were analyzed for normality. Appropriate transformations were required for skewed variables prior to analyses. Allele frequencies were computed by allele counting. Concordance of genotype frequencies with Hardy Weinberg equilibrium (HWE) was tested with χ2 goodness of fit. We investigated the relationship between genotype and all biochemical and clinical variables by ANOVA and the linear differences in genotype associations by trend test. These genotypic associations were also tested with the dominant and recessive models. We generated weight, height and BMI internal sex-specific standard deviation (SD) scores. We modeled the progress of the median, spread and skewness of the measurements as age increased. For each subject we interpolated values linearly between successive SD scores to estimate SD scores at 6 months and at birthdays from 1 to 21 years. The interpolated values were used if measurements were made within 6 months (up to 1 year), 1 year (age 2 years), 1.5 years (age 3 years) and 2 years . Back-transformation provided estimates of measurements at these ages. In order to measure changes in early-life BMI and height (growth), we used the conditional SD scores method. We divided growth into three periods: birth to 2 years (infancy), 2-11 years  and 11 years to adulthood (adolescent growth). To describe growth during each interval, for example between 2 and 11 years, we regressed SD scores at the end of the interval (11 years) on SD scores at the beginning (2 years) and at all preceding time points , and expressed the residuals as SD scores. This produces uncorrelated variables describing change between specific ages . We also conducted multiple linear regression analyses for evaluating the associations after adjustment for confounders.APOA5 (-1131T > C) (18.7%), followed by PPAR-γ (Pro 12Ala) (11.2%). APOA5 (S19W) minor allele was rare (4.0%). The genotype frequencies at all the polymorphisms did not deviate from the Hardy-Weinberg equilibrium (p > 0.05).The allelic and genotype frequencies of the four evaluated SNPs are depicted in Table The inter-relationship between the four polymorphisms and lipid variables for both sexes combined is depicted in Table APOA5 (-1131T > C) SNP and serum triglyceride level was considerable . Serum cholesterol was also significantly higher in subjects with CC genotype (p = 0.007 for linear trend). Associations with other lipid variables were not significant. In view of the low minor allele frequency (MAF) of APOA5 S19W, a combined analysis of heterozygous (SW) and homozygous subjects for W allele (WW) was considered to be more pertinent. Although triglyceride concentration tended to be higher and HDL concentration lower in subjects with minor allele, the differences were not statistically significant by recessive model . No consistent significant associations were observed between APOA5 (S19W) polymorphism and any of the other evaluated outcome measures.A significant difference in triglycerides was evident with subjects having "CC" genotype showing the highest mean triglyceride levels (p < 0.0001 for linear trend). This association remained significant when males (p < 0.001) and females (p = 0.046) were analyzed separately. The age, sex and BMI adjusted effect size per allele of the linear association between PPAR-γ (Pro 12Ala) and any of the evaluated outcome measures. The significant association with serum triglyceride in dominant model (p = 0.029) was not evident in recessive model (p = 0.671).For HL (C-514T), HDL2 was higher in subjects with the minor allele (p = 0.002 by linear trend and p < 0.0001 by recessive model). This association remained significant in males when analyzed separately whereas it was weaker in females (p = 0.011). The significant association between C-514T variation in hepatic lipase and HDL2 subfraction persisted even after adjustment for age, gender and BMI (p = 0.002). There was a significant association of minor allele with serum triglyceride (p = 0.029 and p = 0.008 dominant model). No consistent significant associations were observed between polymorphism at PPAR-γ) and impaired glucose tolerance or diabetes (Table PPAR-γ (Pro 12Ala) SNP and hypertension (p = 0.042).There was no significant association with any of the four polymorphisms and the presence of hypertension , With the dominant model, except for three, no other associations were significant. The APOA5 (-1131T > C) minor allele was significantly associated with a higher BMI at birth (p = 0.001) and lower conditional BMI at 2 years (p = 0.05). HL (C-514T) minor allele was significantly associated with lower conditional BMI at 2 years (p = 0.034).Participants had a mean (SD) of 23 (5.5) observations between birth and the age of 21 years. Association between BMI at birth and conditional BMI at later ages and gene variants is given in Table HL C-514T. There was evidence of a significant negative (p = 0.022) interaction between -1131T > C polymorphism in APOA5 and C-514T polymorphism in hepatic lipase for their age, sex and BMI adjusted association with serum triglyceride levels . However, the combination of a minor allele of APOA5 or hepatic lipase with the minor allele of the other gene (hepatic lipase or APOA5) was associated with a decline  in serum triglyceride level  subjects had a minor allele of both APOA5 -1131T > C and APOA5, hepatic lipase and PPARγ and serial changes in body mass index from birth to adulthood. In our study, APOA5 1131T > C minor allele was associated with significantly higher triglycerides and that of HL C-514T was associated with higher HDL2. PPAR gamma Pro12Ala variation was associated with a lower conditional weight at 6 months in heterozygous subjects and those homozygous for minor allele. APOA5 S19W was associated with a higher conditional BMI at 11 yrs in heterozygous subjects and those homozygous for minor allele. None of the other associations between the gene polymorphisms and serial changes in body mass index or weight from birth to young adulthood were statistically significant.To the best of our knowledge no study has evaluated the relationship of polymorphisms in APOA5 -1131T > C was more prevalent than the S19W polymorphism in the NDBC . Chandak et al [APOA5 in 20% and that of S19W in 3% in Pune Indians whereas the allele frequency for both SNPs in UK white subjects were 4% and 6%. The reported prevalence of -1131C allele from other parts of the world varies between 6.4% in American Caucasian males [The minor allele frequency of an males  and 34% an males  and 15.8We observed that the presence of the -1131C allele was associated with 23.6 mg/dl higher fasting triglyceride concentrations and 9.9 mg/dl higher post-prandial triglycerides. The reported effect size on triglyceride concentration of the less common "C" allele varies from about 30% in Caucasians  to 36% iWe observed a minor allele frequency of 22.9% for C-514T polymorphism in hepatic lipase. The minor allele frequency of 0.15-0.21 has been reported among Caucasians, 0.45-0.53 among Africans and 0.47 among Japanese suggesting considerable ethnic differences. However, a meta-analysis of 25 studies involving nearly 25,000 subjects reported an overall T allele frequency of 25.3% . Plasma APOA5 and hepatic lipase on triglycerides and HDL2 sub-fraction, we investigated the interaction between these SNPs in determining triglyceride levels. It was interesting to note the attenuation of the effect of APOA5 variant on triglycerides in the presence of polymorphism in hepatic lipase and vice versa. Mutation in either of the gene in the presence of a normal genotype in the other gene was associated with higher triglycerides as compared to mutation in both the genes. We could not assess the dietary fat intake, which may interact with HL and APOA5 polymorphisms to determine APOA5 and HL activity.Since the only significant effect we found were that of APOE, APOC3 and PPARγ2 gene polymorphisms on lipid levels in people with low birth weight. Low birth weight was associated with higher total cholesterol, LDL cholesterol, and apoB/apoA in males with APOE ε3 ε4 genotype whereas in males the genotype was associated with lower HDL and higher triglycerides. There were no associations between low birth weight and blood lipids in any PPAR-γ2 genotypes. Effect of APOE genotype on total cholesterol, LDL and ApoB has also been reported by others in children with low birth weight [in utero nutritional events. No group has examined influence of APOA5 polymorphism on association between birth weight and blood lipids till date. We failed to find any interaction between APOA5 and birth weight on lipids in our study. Limitation of the NDBC study is that we have not captured current dietary intake and current physical activity which may have an important bearing on lipid levels.We did not find any interaction between birth weight or early growth and the analyzed polymorphisms in determining lipid levels in later life. Ruiz et al  studied h weight ,24. The PPAR-γ Pro12Ala genotype on lipid levels. Data on interaction of birth weight and PPAR gamma in determining lipids has been inconclusive with one group underlying the influence of PPAR-γ genotypes on the association between birth weight and lipid levels among elderly people [PPAR-γ2 genotype on lipids [We did not find any significant interaction between birth weight and y people  and othen lipids ,26. ThesAPOA5, PPAR-γ and HL do not have any significant relationship with the birth weight and serial changes in anthropometry from birth to adulthood. The promoter polymorphism in APOA5 is associated with a raised serum triglyceride levels; the age, gender and BMI adjusted effect size being substantial. The promoter polymorphism in hepatic lipase is associated with higher HDL2 levels. An interaction between polymorphisms in APOA5 and hepatic lipase seems to influence the serum triglyceride levels which need to be further explored.In conclusion, our study shows that polymorphism in The authors declare that they have no competing interests.RL wrote the first draft of the manuscript and was responsible for the analysis. HPS, MS and KSR and SB helped design the study. GRC helped in study design and writing of manuscript. RA performed the gene analysis. SP and SB performed repeat analysis of SNP's for quality assurance, DG and SS carried out the statistical analysis, YS carried out the biochemical analysis. All authors helped in conduct of the study, contributed to the redrafting of the manuscript, and approved the final manuscript.


PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes.Background: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase  metabolite concentrations, with gestational age and birth weight.192PON1 and –108PON1 genotypes.Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (ΣDAP) with gestational age and birth weight. We also examined whether these associations differed according to infant 192QRPON1 and –108CTPON genotypes.Results: Among 306 mother–infant dyads, a 10-fold increase in ΣDAP concentrations was associated with a decrease in covariate-adjusted gestational age  and birth weight ; the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between ΣDAP concentrations and gestational age was stronger for white  than for black  newborns. In contrast, there was a greater decrease in birth weight with increasing urinary ΣDAP concentrations for black  than for white  newborns. Decrements in birth weight and gestational age associated with ΣDAP concentrations were greatest among infants with 192PON1/108 genotypes.Conclusions: Prenatal urinary ΣDAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and  Silent Spring  insecticides, in her book t Spring . In partt Spring . Althougt Spring .The developing fetus may be especially vulnerable to OP pesticides because of its small size, rapid growth and development, and limited ability to detoxify harmful substances . Animal PON1 gene affect the function, production, and efficiency of PON in the body; recent studies have focused on two alleles: 192PON1 and –108PON1 ; for 192PON1, they found DAP-associated reductions in gestational age for QQ infants, and weaker associations for the RR or QR groups. However, 192RRPON1 as the more susceptible group, reporting stronger negative associations between diethyl alkyl phosphate (DEAP) metabolites and birth weight, and between dimethyl alkyl phosphate (DMAP) metabolites and birth length, in mothers with the 192RRPON1 genotype (compared with those with QQ genotype). Paraoxonase (PON) is an enzyme that detoxifies several OP pesticides, including chlorpyrifos, parathion, and diazinon . SeveralPON1–108 . Brieflysticides . In epidPON1 distributions differ across racial groups  and to be low birth weight , both of which place newborns at risk for adverse health outcomes . Racial l groups .192QQPON1 or –108TTPON1 genotypes.The purpose of this study was to examine the relationship of prenatal OP insecticide exposure, measured using urinary concentrations of six DAP metabolites, with gestational age and birth weight in a birth cohort from Cincinnati, Ohio. We hypothesized that gestational OP exposure would be associated with shorter gestation and lower birth weight. We also hypothesized that the relationship between urinary OP exposure and birth weight/gestational age would be greatest among infants with Study sample. We used data collected from mothers and newborns enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, an ongoing prospective birth cohort. Subject recruitment and interviews for the HOME Study have been described elsewhere  for analysis. We measured six urinary DAPs—dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP), which are common metabolites of about 75% of the OP insecticides used in the United States—using a modification of the analytical method of Quality control (QC) materials, prepared at CDC from spiked pooled urine, were analyzed with standards, blanks, and study samples. The QC concentrations were evaluated using standard statistical probability rules . The lim10-transformed the averages to achieve a more normal distribution.We converted the metabolite concentrations from micrograms per liter to their molar concentrations (nanomoles per liter) and summed them to obtain overall concentrations of diethyl alkyl phosphates , dimethyl alkyl phosphates , and of all six metabolites (ΣDAPs). We used creatinine as a marker of urine dilution and obtained creatinine-standardized DAP concentrations by dividing metabolite concentrations by creatinine concentration . To avoiOutcome and covariate measures. We abstracted birth weight from medical records, and calculated gestational age from the mother’s self-reported date of last menstrual period. When this information was not available, we used the results of an ultrasound (n = 7) or a Ballard examination performed just after delivery (n = 3) to determine gestational age. Demographic factors  were obtained from subject interviews. We also characterized infant size using race-specific birth weight for gestational age z-scores  to determine whether infants’ growth was restricted relative to their length of gestation  were excluded from the analysis. Blood lead and serum cotinine were quantified using previously described methods at the CDC laboratories . Genotyping was conducted at the Cincinnati Children’s Hospital Medical Center DNA sequencing and genotyping core facility. We used the Applied Biosystems predesigned TaqMan assays  for rs662 (192Q/R) and rs705379 (–108C/T) with 15 ng of genomic DNA. The protocol was as per the manufacturer’s recommendations in 384 well format, including 16 blanks and 4 sets of 2 controls for QC purposes. Assay plates mixing reagents and DNA were prepared using a TECAN Evo200 robotic laboratory workstation  and amplified in an ABI 9700 thermocycler (Applied Biosystems). TaqMan results were read on an ABI 7900HT real time PCR system and exported in Excel format using the ABI SDS 2.4 software (Applied Biosystems). Genotype data was available for 312 of 344 (90.7%) of infants, with 300 (87.2%) having identifiable SNPs at both PON1 sites.Statistical analysis. For multivariable analysis, we used PROC GLM in SAS version 9.1 . We began with an a priori set of covariates that have been consistently associated with gestational age and birth weight: maternal age, education, race/ethnicity, and marital status; household income; gestational age at initiation of prenatal care; and parity. We also considered the following covariates: depressive symptoms (measured by the Beck Depression Inventory-II) (p < 0.2) with both DAP concentrations and birth outcomes were included in our multivariable analyses. Only blood lead and serum cotinine concentrations fit these criteria. Our final model included maternal age (continuous), race/ethnicity (black or white), and marital status (married or not married), household income (contiuous), parity , and blood lead and serum cotinine concentrations (log10-transformed). We did not include gestational age in the primary birth weight analysis because of its potentially being on the causal pathway. However, for comparison with prior results in other cohorts, we constructed gestational age-adjusted models in a sensitivity analysis.tory-II) , IQ, insWe assessed the form of the exposure–response relationship using locally weighted regression (LOESS) plots of log-transformed concentrations and outcomes. Because a straight line fit inside the 95% confidence bands, we concluded that it was appropriate to use a linear term to describe the relationship.p < 0.1 as the criteria for a statistically significant interaction.Based on our preliminary analyses, we observed that the pattern for associations of DAP concentrations and birth outcomes varied by race/ethnicity. Because almost all mothers identified themselves as either black or white (the “other” group contained only 15 mothers), we restricted our analyses to black and white mothers. We then ran race-stratified models to obtain effect estimates, and formally assessed interactions in separate models using cross-product terms between race and urinary OP pesticide metabolite concentrations, using PON1 genotype and OP pesticides, we ran several PON-stratified analyses, stratifying by 192PON1 or –108PON1. We also formally assessed interactions using dummy variables and interaction terms. Because race appeared to be an effect modifier and PON1 genotype can vary across racial groups, we also ran the PON1-stratified analyses separately for black and white mothers whenever possible given sample sizes.To examine gene–environment interactions between 10-transformed mean urinary creatinine concentrations as a covariate, as suggested by We also performed several sensitivity analyses. First, we examined whether mothers’ pregnancy medical conditions might confound the relationship between urinary DAP concentrations and birth outcomes. These included abruptio placenta, placenta previa, chorioamnionitis, preeclampsia, and pregnancy-induced hypertension. Next, we examined whether relationships between DAP concentrations and birth weight were evident for only term newborns (≥ 37 weeks) . We consn = 31, 9.0%) or were low birth weight .Mothers participating in the study were predominantly white, 25–35 years old, married, and primiparous . Househor = 0.22). ΣDMAP metabolite concentrations  were considerably higher than those of ΣDEAP metabolites . The median blood lead concentration was 0.66 µg/dL (IQR = 0.51–0.87), and the median serum cotinine level was 0.027 ng/mL (IQR = 0.01–0.18). In the final models, we dropped one mother because of a missing creatinine value, 22 because of missing covariate values, and 15 in the “other race” category, giving us a final sample size of 306.All mothers had detectable levels of at least one DMAP metabolite, and at least one DEAP metabolite was detected in 92.7% of women. The ΣDAP metabolites median was 81.3 nmol/L (IQR = 42–220) . ConcentPON1 genotype was also associated with maternal race/ethnicity in the study sample. Infants born to white mothers were more likely to have 192QQPON1 (51.4% vs. 12.7%) and –108PON1CT genotypes (45.7% vs. 20.0%) than infants born to black mothers. Infants with black mothers were more likely to have 192PON1RR (44.3% vs. 10.4%) and –108PON1CC (76.3% vs. 29.8%) genotypes .In multivariable analysis, a 10-fold increase in ΣDAP concentrations, which corresponds roughly to a shift from the 15th (29.5 nmol/L) to the 85th percentile (318.0 nmol/L) of the distribution, was associated with a 0.5-week decrease in gestational age  . Associap = 0.10. In contrast, ΣDAP concentrations were associated with a larger decrease in birth weight among black newborns than in white newborns, although the interaction was not statistically significant (p = 0.46). Once we adjusted for gestational age, however, we observed a slightly weaker but statistically significant inverse association between ΣDAP concentrations and birth weight for black newborns, and the interaction for ΣDAP concentrations and birth weight by race/ethnicity became statistically significant (p = 0.02). We also found a nonsignificant inverse relationship between urinary OP metabolite concentrations and birth weight for gestational age . The relationship was stronger among blacks  than whites .In race-stratified models, ΣDAP concentrations were associated with shortened gestation in white newborns, but not in black newborns . The intPON1-stratified models, we observed the strongest associations between ΣDAP concentrations and birth weight and gestational age in the heterozygous groups: 192QRPON1 and –108CTPON1 . Several interaction terms between PON1 genotypes and ΣDAP concentrations were statistically significant. Looking at models stratified by race and PON1 status, numbers of observations in many of the categories were too small to produce stable point estimates. However, in almost all cases we observed the strongest associations between DAP metabolites and birth outcomes appearing in the heterozygous groups. We found no evidence for main effects of PON1 genotype on either birth weight or length of gestation (data not shown).In Sensitivity analyses. Medical conditions were associated with birth outcomes and DAP urinary concentrations (n = 9), placenta previa (n = 1), chorioamnionitis (n = 1), pre-eclampsia (n = 15), or pregnancy-induced hypertension (n = 9) had shorter gestations and lower-birth-weight newborns than the rest of the study population (data not shown). These mothers also had higher median DAP urinary concentrations than mothers without the conditions  attenuated the effect estimates for a 10-fold increase in ΣDAP concentrations for both gestational age  and birth weight , but the patterns were consistent with our primary results. Stratifying full-term births by race produced results that were similar to those for preterm and term births combined: Associations with birth weight were stronger among black newborns than white newborns, whereas estimated effects for gestational age were stronger in white newborns than black newborns. We did not find any suggestion of an interaction between child sex and ΣDAP concentrations for either gestational age or birth weight (p > 0.3).Restricting analyses to full-term births  did not change the pattern of results (data not shown). Finally, associations obtained when using ΣDAP concentrations from individual spot urine collections were slightly attenuated compared with the average of the 16- and 26-week collections, for both the 16-week  and 26-week samples .Using non-creatinine-standardized ΣDAP concentrations modestly attenuated the observed estimates: In the full group, the gestational age coefficient was –0.3 weeks  and the birth weight coefficient was –100 g . Adjusted coefficients in all secondary analyses were closer to the null without creatinine adjustment, but the pattern with respect to race remained the same (data not shown). Likewise, excluding women with urinary creatinine values < 20 mg/dL  the estimated z-score decrease of 0.4 associated with a 10-fold increase in ΣDAPs corresponds to a decrease of about 160 g .It is unclear why OP insecticides would be associated with shorter gestation in white newborns, but not black newborns. Although black mothers had higher levels of urinary OP pesticide metabolites than white mothers, these metabolites are a nonspecific measure of exposure to various OP insecticides; different OP pesticides may act through a variety of mechanisms, some affecting length of gestation and others affecting fetal growth. Blacks and whites might differentially be exposed to these different formulations of pesticides. Maternal race/ethnicity may also be acting as a proxy for a combination of conditions—socioeconomic factors, genetic susceptibility, psychological stressors, and environmental toxicants—only some of which were measured in our study. We examined several possible confounders, including income, education, maternal depressive symptoms, maternal IQ, insurance status, area of residence, prenatal care, Excluding mothers with specific medical conditions, especially those who had placental abnormalities or chorioamnionitis, attenuated the association of urinary DAP concentrations and perinatal outcomes. Excluding women with hypertensive conditions, which were more common in black mothers than in white mothers, strengthened the associations to a negligible extent.PON1 polymorphisms we examined, the heterozygous groups (192QRPON1 and –108CTPON1) generally showed the largest estimated decreases in birth weight and gestational length associated with log10-transformed ΣDAP concentrations. These results were unexpected, but > 200 polymorphisms of PON1 have been identified, and it may be unreasonable to expect two PON1 polymorphisms to explain the amount of PON produced or its efficiency in detoxifying certain chemicals  OP pesticides, particularly for dietary exposures . UrinaryPON1 status might shed more light on PON-mediated susceptibility than infant PON1 genotypes alone. Other strengths of this study are that we presented data from a racially and demographically mixed birth cohort in a sample, intentionally enriched with black women, from the Cincinnati metropolitan area. We also controlled for a wide range of confounders, including continuous measures of lead and tobacco exposure, and pregnancy medical complications, and our findings were robust to several sensitivity analyses.The reliance on self-reported dates of last menstrual period to determine gestational age represents another limitation . This mePON1 genotype status. Although the prior literature on gestational OP exposure and birth outcomes is inconclusive, several studies have observed associations between adverse health outcomes in children and maternal exposure to OP insecticides during gestation, including abnormal reflexes  PDFClick here for additional data file.


Purpose. There is a paucity of data regarding EMS stretcher-operation-related injuries. This study describes and analyzes characteristics associated with undesirable stretcher operations, with or without resultant injury in a large, urban EMS agency. Methods. In the study agency, all stretcher-related “misadventures” are required to be documented, regardless of whether injury results. All stretcher-related reports between July 1, 2009 and June 30, 2010 were queried in retrospective analysis, avoiding Hawthorne effect in stretcher operations. Results. During the year studied, 129,110 patients were transported. 23 stretcher incidents were reported . No patient injury occurred. Four EMS providers sustained minor injuries. Among contributing aspects, the most common involved operations surrounding the stretcher-ambulance safety latch, 14/23 (60.9%). From a personnel injury prevention perspective, there exists a significant relationship between combative patients and crew injury related to stretcher operation, Fisher's exact test 0.048. Conclusions. In this large, urban EMS system, the incidence of injury related to stretcher operations in the one-year study period is markedly low, with few personnel injuries and no patient injuries incurred. Safety for EMS personnel and patients could be advanced by educational initiatives that highlight specific events and conditions contributing to stretcher-related adverse events. The majority of patient transportation in the prehospital emergency medical care environment involves the use of mobile stretchers. Stretcher utilization occurs in three distinct phases: (1) unloading from the ambulance; (2) loading into the ambulance; (3) transporting over surface structures. Several commercially manufactured devices have been designed to best accomplish these activities. Constraints on the stretcher system are myriad, including weight and size of the patient, ease of use, and durability. With these limitations in mind, finding the balance of performance and safety is an important mission.http://www.ncbi.nlm.nih.gov/pubmed) searching with the unrestricted term of  “ambulance stretcher” yields few relevant investigations [ Thus, ambulance stretcher operations constitute a necessary, yet risky, part of the provision of prehospital emergency medical services. Despite generally widespread acknowledgement of risk to patient and EMS professional alike, there remains a paucity of data addressing ambulance stretcher associated injury analysis. A review of the past decade's literature in the PubMed database  of any data measuring the injuries related to stretcher “adverse events.” As many in EMS will know, there is widespread recognition of the potential for EMS professionals to sustain back injury in the performance of basic patient transportation. Many entrepreneurial ventures utilize this concern of back injury risk in marketing new stretcher designs and stretcher lifting and loading capabilities. Certainly, no national organization tracks all relevant incidents of ambulance stretcher-related injuries. In the present era, despite the presence of many groups advocating for increased safety in prehospital emergency medical care, it appears unlikely there will be significant movement towards comprehensive reporting that could facilitate widespread evidence-based progress in limiting stretcher-related injuries. Against this important background, we sought to critically analyze the types and frequencies of injuries sustained by patients and EMS professionals directly related to stretcher operations occurring in a large, urban EMS system in the southwestern United States. This investigation was additionally conceived to design educational initiatives for purposes of injury prevention as well as to add knowledge in this important, yet underreported, arena.This was a retrospective, observational study of all patient transports conducted in a single large, urban EMS system. The event of interest was an injury sustained by a patient and/or EMS professional directly related to use and operation of the stretcher.The study EMS agency, Emergency Medical Services Authority (EMSA), is a public utility model agency serving central and metropolitan Oklahoma City and Tulsa, OK. The two geographical service areas combined comprise approximately 1100 square miles and are populated by 1,201,232 residents. . In thisEMSA mandates that all adverse events related to stretcher transport of a patient, however minor in force or resultant injury, are reported by the involved EMS personnel utilizing incident reporting; these reports, with details entered as free text, are logged and maintained in a computerized database . The study period was chosen by convenience and by inclusion of all weather seasons to be from July 1, 2009 to June 30, 2010.All stretcher-related incident reports related to patient movements during this study year were queried. These incident reports were compiled by the Safety and Risk Manager for EMSA and reviewed in detail by two of the researchers  for appropriate inclusion in the study as well as for agreement upon descriptive characteristics of contributing factors and sustained injuries. Data recorded included the nature of the adverse event as well as any documented contributing factors, patient body habitus if notably obese, patient behavior if notably combative or otherwise physically disruptive, timing of incident , and presence of suspected injury to the patient and/or EMS personnel. All events were categorized into three time periods: unloading, loading, and surface movement. Subtype characterizations included equipment failure, safety latch malfunction, poor surface conditions, obese patient, and uncooperative patient. The data were abstracted into a spreadsheet using Microsoft Excel .A priori analytical emphasis was placed upon unloading or loading patients. These timeframes are generally accepted as events of requiring higher energy to safely move patients, and thus, events that seemed particularly likely to contribute to injury.The primary outcome measure was the rates of stretcher operation associated injury to patients and to EMS professionals. These rates were assessed using the analytical methods described below. The secondary outcome measure was assessment of the particular contributing factors and timeframes of stretcher operation associated with stretcher-related incident reports filed by EMS personnel. The primary analytic approach followed the general lines of the reporting in the previous study by Wang et al. Because of our having the total number of “exposures” (transports), we were also able to execute event rate calculations. The number of stretcher events was determined, and an event rate per 1,000 transports was calculated; 95% Poisson confidence intervals (CIs) were then calculated around the overall estimate for event rates. For construction of CIs in which the point estimate was zero , a one-sided 97.5% CI was calculated. For proportional data , binomial exact 95% CIs were calculated.P < 0.05 (95% CI) level. STATA 11 MP  was used for all testing. For comparative analyses, lack of overlap between CIs was taken as indicative of statistical significance. For tabular data, results were analyzed using Fisher's exact text. For analyses, significance was defined at the This study protocol was reviewed and approved by The University of Oklahoma Health Science Center Institutional Review Board.The entire costs of this study were borne by EMSA and the OU Department of Emergency Medicine. Stryker Corporation (the manufacturer of the stretchers utilized throughout the study period) had no association with (or knowledge of) this study. Stryker Corporation did not fund the study and did not provide study-associated product pricing to EMSA.During the study year period, the EMS agency transported 129,110 patients. There were 23 adverse stretcher events reported, yielding an event rate of 0.018 per 1,000 transports. Stretcher events were relatively evenly divided (44% and 56%) between the service's two geographic locations (Oklahoma City and Tulsa). There were no patient injuries . There were 4 EMS provider injuries, event rate 0.031 per 1,000 transports . All EMS injuries were minor and no time off was requested or required due to these injuries. These included 2 knee injuries and 2 back injuries. The timing of reported adverse stretcher events was analyzed . The majIn addition to the timing of the event, we also investigated contributing factors . In someP = 0.63) between location, Oklahoma City or Tulsa metropolitan service area, and cause of incident . There was also no association between location and whether stretcher events occurred during patient movement (P = 0.11). For other analysis, events from each of the two EMSA metropolitan service areas were combined. There was also no association (P = 0.048). Overall numbers of outcomes were too low to allow for multivariate exploration of this endpoint. No other factor was found to have a significant associated with provider injury, although low event numbers precluded a robust statistical analysis.Since there were no patient injuries, no analysis could be performed for factors associated with patient injury. Univariate analysis of the endpoint “crew injury” revealed an association between that endpoint and the type of stretcher problem: patient factors (weight) were positively correlated with increased risk of crew injury (In this study, the incidence of adverse events related to stretcher operations is markedly, if not surprisingly, low. There were few personnel injuries and no patient injuries during the study period. Hawthorne effect was possible, but not likely due to retrospective study nature and study time comprising one year. Anecdotally, the study service has rarely experienced adverse stretcher operations leading to lost work productivity and at least minor patient injury. For these reasons and in additional prevention efforts, this study was conceived to establish baseline stretcher-related adverse event and sustained injury rates to benchmark educational and operational initiative impacts. The study year was chosen at random and specifically was not chosen with any predetermination of results. While adverse events and resultant injury can occur during any phase of stretcher operations and due to multiple contributing factors, this study does help to delineate higher likelihood times and factors. The stretcher safety latch, mounted on the ambulance floorboard, proved prominent in this analysis of related factors. Adverse incidents more frequently occurred if the stretcher did not “catch” on this latch when being retracted from the ambulance, thereby preventing a more controlled unloading of the patient without unexpected carriage collapse, itself either partial or complete. The proper safety latch-stretcher interface, should be stressed to EMS personnel in both initial and continuing training regarding safe stretcher operations. It is important for EMS personnel to be aware of these composite results in order to further protect themselves and maintain patient safety. Additional investigation into this topic is greatly needed to attain firmer established insights into necessary injury-avoidance training in ambulance stretcher operations. It is discouraging to find such paucity of available peer-reviewed data addressing results of specific interventions designed to improve related safety. Perhaps a prevailing belief that little can be done outside of generic safe movement and lifting instructions persists to an extent that few academic studies of EMS stretcher operations are endeavored. Clearly, new patient transport and lifting devices designed for EMS use encourage such inquiry; our hope is this study will serve as an impetus for further evaluation of such technology.An obvious limitation of the study is dependence upon EMS personnel to self-report adverse events related to stretcher operations. Within the study agency, a culture of safety is fostered, promoting self-reporting of these incidents to assist in injury prevention, limiting concern of EMS personnel regarding untoward employment repercussion for such reporting. In reality, the repercussion of “not reporting” a later discovered event is substantially more stringent. Serious patient injury in this realm would most likely be additionally discovered through patient or legal surrogate complaint, including litigation initiation. Particularly minor injuries could have been missed by EMS providers, especially if not verbalized by affected patients. Low absolute numbers of ambulance stretcher-related patient and EMS professional injuries occurring during the study period are markedly advantageous in injury prevention and operational efficiency paradigms. From an academic inquiry view, these low numbers are not given to form statistically robust conclusions. Thus, our results should be considered preliminary. Further similar data collection in this and other large volume EMS systems will aid in determining if a larger dataset will result in narrower confidence intervals with resultant higher statistical significance. Multivariate analysis of these suggested larger data sets will aid in determining if specific interventions are warranted against discrete types of situations more prone to ambulance stretcher-related injuries. Additionally, EMS systems utilizing different stretchers may not find direct applicability of these findings.In this large, urban EMS system, the incidence of injury related to stretcher operations in the one-year study period is markedly low, with few personnel injuries and no patient injuries incurred. EMS personnel should be aware of the risk of injury to themselves that can occur during stretcher operations when moving morbidly obese and/or combative patients. Safety for EMS personnel and patients could be advanced by educational initiatives that highlight specific events and conditions contributing to stretcher-related adverse events.


Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30 kg/m2; the cross product term for IGF-I and maternal BMI was statistically significant (P ≤ 0.0004). Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity.At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation) were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130 g heavier at birth, ( Low birth weight (LBW) and high birth weight (HBW) are both important indicators of suboptimal intrauterine development and have been linked to risk of several chronic diseases later in life. HBW has been associated with childhood and adult obesity  and someIGF-I is a mitogenic and antiapoptotic paracrine growth factor expressed in all fetal organs , 9, and Ethics Statement. The study protocol was approved by the Duke University Institutional Review Board (IRB). We obtained written informed consent from all participants involved in our study. We also obtained informed written consent from carers or guardians on the behalf of the minors/children participants involved in our study.n = 757). IGF-I analyses were performed on the first 251 women and had a gestational age ≥37 weeks. Data from these participants were comparable to participants in whom IGF-I was not measured with respect to maternal age, gestational age, race/ethnicity, and maternal prepregnancy BMI.Pregnant women were enrolled as part of the Newborn Epigenetics STudy (NEST), a prospective study of women and their infants. Detailed methods for enrollment of study participants have been reported elsewhere . BrieflyInterviewer- or self-administered questionnaires were obtained at the time of enrollment and medical records during pregnancy were abstracted at parturition. Data collected using questionnaires included sociodemographic characteristics, reproductive factors, and lifestyle factors such as cigarette smoking and self-reported prepregnancy anthropometric measurements. Information on anthropometric measurements during pregnancy, birth outcomes, including birth weight and length, was abstracted from medical records. Umbilical cord blood specimens were also collected at birth, as previously described , 37. Plasma concentrations of IGF-I were measured using microplate enzyme-linked immunosorbent assays  according to the manufacture instructions, and triplicate assays per sample were performed. Absorbance was read using a microplate reader . The plasma IGF-I concentrations ranged from 3.65 ng/L to 418.36 ng/L, and assay sensitivity was 2.2 ng/mL.2); race/ethnicity ; and maternal education , maternal smoking, and infant gender. Although some of these factors were not statistically significantly associated with BW in this study, we adjusted for maternal age, BMI, race, education, delivery route, gestational age at delivery, maternal smoking during pregnancy, and infant gender, as they are associated with BW and IGF-I in the population. The distribution of IGF-I levels departed from normality and thus they were categorized into tertiles. We then dichotomized at the top tertile (67th percentile) and compared this tertile  to the remainder . Linear regression models were used to examine the extent to which IGF-I levels differed by birth weight, as described in [Infant birth weight was normally distributed and was used as a continuous variable. Because both high birth weight (HBW) and low birth weight (LBW) have been linked to maternal obesity , we alsoribed in . All staP = 0.006) . = 0.006) . P = 0.65), race (P = 0.83), maternal education (P = 0.38), maternal smoking (P = 0.63), obesity (P = 0.28), and gestational age (P = 0.91) (P = 0.14). Median IGF-I concentration in newborns was 35.55 ng/L  with a mean of 58.92 ng/L. Birth weight ranged between 2000 and 5160 g . Infants with higher levels of IGF-I (>3rd tertile) were born slightly heavier than infants with lower IGF-I concentrations (≤3rd tertile), although the differences were not statistically significant. Infants with higher IGF-I levels were comparable to those with lower levels with respect to maternal age ( = 0.91) , althougβ's) and their standard errors (SEs) for five multivariate linear regression models of birth weight on IGF-I levels, in which IGF-I ≤67th percentile concentrations or ≤3rd tertile served as referents; one for all participants, one restricted to African Americans, one restricted to Whites, one restricted to maternal BMI <30, and one restricted to maternal BMI ≥30. The first model shows that after adjusting for infant gender, race, gestational age at delivery, delivery route, maternal BMI and smoking during pregnancy, infants in the upper tertile of IGF-I were larger at birth , corresponding to 130 g increased birth weight in infants born to those with high IGF-I levels (P = 0.002) compared to White infants (P = 0.02). However, the cross-product term for race and IGF-I was not significant (P = 0.5). Since the prevalence of BMI ≥30 in African American women in our study is higher (67%) compared to Whites (24%) (P < 0.0001), we examined the role of maternal BMI on the relationship between IGF-I levels and birth weight. The pair of models restricted by BMI revealed that the association of IGF-I levels and infant size was limited to women with a BMI ≥30 . We found a strong positive association in infants born to obese women; the cross-product term for maternal BMI and IGF-I was P = 0.0004. I levels . We alsoOur key finding was a positive association among term infants with elevated IGF-I levels and an increased risk of higher birth weight. This positive association was most apparent in infants born to obese women. High birth weight and high IGF-I levels—a potent mitogen—have been linked to CVD, T2D, and some cancers . ImportaThe extent to which the positive association between IGF-I at birth and early postnatal growth that is maintained during life course to adulthood is still unclear, although a few studies report that elevated IGF-I levels measured at birth are associated with age 4-5 year obesity , 39.IGF-I levels found in this study  are slightly lower than those reported in previous studies ; howeverThese race/ethnic similarities exist despite IGF-I concentrations being generally lower in African American than in White neonates born with normal weight, as shown in male  and in f Our findings that elevated IGF-I levels are associated with increased birth weight in infants born to obese mothers, are consistent with at least three other studies comprising European, Maori, South Asian, and Pacific Islands' cohorts , 47, 48,The main limitation of this study was relatively small sample size for analyses restricted to maternal BMI (BMI < 30 versus BMI ≥ 30); however, findings are consistent with the expected role of IGF-I, and IGF-I values themselves  and the magnitude of the positive associations with higher birth weight and growth are similar to previous reports , 26. AlsIn summary, we found that elevated IGF-I levels in newborns increase the risk of higher birth weight in African American and White infants. Our findings also suggest that maternal BMI ≥30 may modify positive associations between IGF-I and higher birth weight, supporting the idea that maternal obesity may be key in increasing the risk of higher birth weight in the newborns, an important risk factor for several chronic diseases, including cancer. These findings suggest that the potential utility of IGF-I levels as a marker of future obesity in the offspring is limited to those born to obese women. As the prevalence of maternal obesity continues to increase, larger multiethnic studies with followup at shorter intervals that allow for maternal obesity-specific analyses are required to further elucidate the nature of the positive association between IGF-I levels and higher birth weight.


Intrauterine growth restriction (IUGR) and small for gestational age (SGA) birth have been considered possible indicators of the presence of malformations. The aim of this study is to evaluate such relationships in a population of newborns, along with other epidemiological and auxological parameters, in particular the ponderal index (PI).We analyzed the birth data of 1093 infants, classified according to weight for gestational age as SGA, appropriate for gestational age (AGA) or large for gestational age (LGA). The prevalence of malformations was analyzed in relation to weight percentile at birth and SGA birth, maternal smoking, pregnancy diseases and PI.Our analysis showed no significant relationship between the prevalence of malformations and SGA birth. Maternal smoking and pregnancy diseases were strongly related to SGA birth, but not to a higher prevalence of malformations. PI, however, had a significant relationship with a higher prevalence of malformations, if analyzed as either a continuous variable or a categorical variable (cutoff: < 2.4).The association between congenital malformations and birth weight for gestational age seems to be weak. As part of diagnostic screening for malformations in the neonatal period, PI could be considered a better predictor of risk than weight percentile. Intrauterine growth restriction (IUGR) can be either symmetric or asymmetric. Symmetric IUGR is characterized by a similar and proportionate reduction in all auxological parameters, including weight, length, and cranial and abdominal circumference. On the other hand, asymmetric IUGR is characterized by a greater reduction in body weight, when compared to length. The diagnosis of IUGR is not always easy or direct; small for gestational age (SGA) birth is usually considered an indirect indicator of IUGR, even if these two concepts are not identical.It is thought that IUGR is related to the presence of congenital malformations due to at least two possible pathogenetic mechanisms ;growth retardation occurs as a result of a congenital malformationgrowth retardation and congenital malformations occur as different manifestations of a common, independent etiological factor.The offspring of multiple pregnancies show an increased incidence of prematurity, a lower birth weight and a higher prevalence of congenital malformations at birth .Lituania et al. found a higher risk of malformations in newborns with IUGR; they suggest that antenatal IUGR, especially when found to occur during the early stages of pregnancy, may be caused by the presence of malformations and chromosomal abnormalities . Khoury Dashe et al. analyzed the prevalence of malformations in newborns appropriate for gestational age (AGA), or with symmetric SGA, versus those with asymmetric SGA. They found in their cohort that asymmetric SGA infants were at significantly higher risk of major malformations (14%) compared with AGA and symmetric SGA babies . In addition, aneuploidy was more common (p <0.001) in asymmetric SGA newborns (3%), compared with symmetric SGA (1%) and AGA newborns (less than 0.1%) .Other studies have focused on specific types of malformations and chromosomal abnormalities, and on how those specific conditions may be related to IUGR and/or SGA birth. Several case–control studies and case series have analyzed the association between intrauterine growth restriction, low birth weight (less than 1500 grams) or SGA birth, and various types of malformations, such as congenital heart disease  , malformParticularly interesting are the studies on the relationship between IUGR and chromosomal abnormalities and/or genetic syndromes. Several studies, in fact, report that fetuses with chromosomal disorders, including trisomy 13, 21 and 18, often exhibit IUGR. The same has been shown for Turner syndrome. Aneuploidy and genetic syndromes are predominantly associated with asymmetric IUGR ,18. SomeThe aim of this study is to evaluate, in a population of newborns, the possible relationship between the presence of major congenital malformations and various epidemiological and auxological parameters, in particular low birth weight in relation to gestational age (SGA birth) and ponderal index (PI) as a marker of asymmetric intrauterine growth.st 2011 to March 31st 2012. A total of 1093 infants were enrolled, including 34 twins (3.1%). Newborns were classified according to weight for gestational age (GA) in the following categories:using the percentile charts of the Italian Neonatal Study (INeS) 2011 [http://www.inescharts.com/index.aspx), based on standard deviation, that assigns an exact percentile value to each newborn.In this retrospective study, we analyzed the birth data of all inborn babies admitted to the Neonatal Unit of Azienda Ospedaliera Universitaria Policlinico “Paolo Giaccone” in Palermo, from January 1eS) 2011 , and in th percentile;✓ SGA: weight for GA below the 10th and 90th percentiles;✓ AGA: weight for GA between the 10th percentile✓ LGA (large for GA): weight for GA above the 90The PI was computed as follows:The study population was also divided into two categories according to the presence or absence of congenital malformations. Only major malformations were considered.Statistical analysis was performed by the open software R .The best cutoff for PI was determined by an ROC curve analysis, using the R package ROCR .In total, 1091 infants were evaluated (two were excluded because their GA was unknown); 877 (80.38%) were AGA, 76 (6.97%) SGA and 138 (12.65%) LGA.The GA range was 151–299 days, including preterm newborns , term newborns  and post-term newborns .The total prevalence of malformations was 4.85% (53 cases). Table The prevalence of malformations was 5.1% in SGA, 4.8% in AGA and 5.3% in LGA newborns. These small differences were not statistically significant (p = 0.97).Analyzing the distribution of exact weight percentile values according to the presence of malformations, we found that the values were slightly lower in the malformation group Figure . The difIn addition to the presence of malformations, we considered other obstetric factors that can affect birth weight, such as diseases and smoking during pregnancy, to assess their role in determining a condition of IUGR, and their possible relationship with the presence of malformations.Smoking during pregnancy, defined as the average consumption of five or more cigarettes per day, was present in 11.89% of pregnancies. The prevalence of SGA births was significantly higher in pregnancies in which the mother smoked . Smoking during pregnancy, however, was not associated with the presence of malformations; the prevalence of malformations was similar in infants born to smoking and non-smoking mothers .Diseases in pregnancy (or pregnancy-related) were present in 32.11% of the population, as summarized in Table The prevalence of SGA births was significantly higher in mothers with disease , but we found no relationship between maternal disease and malformations, which were present in 3.7% of pregnancies with diseases and in 5.4% of pregnancies without diseases .As SGA babies did not seem to have a higher prevalence of malformations in our sample population, we tried to adopt a stricter definition of IUGR, considering only newborns whose weight percentile was lower than 3 (“extreme SGA”). There were 41 such newborns in our population (3.76%).Again, we could not observe any differences in the prevalence of malformations in the two groups .Finally, we considered the PI, an indicator of asymmetric intrauterine growth, introduced for the first time by Rohrer in 1921. In our population, the PI mean value was 2.67 ± 0.25, median 2.67, range 1.77 - 3.60.Figure To test PI as a categorical variable, we performed an ROC curve analysis using PI as a predictor of malformations. Considering both an accuracy curve and a chi square curve, a value of 2.4 was chosen as the best cutoff in predicting the presence of malformations Figures , 4.We considered as “asymmetric” newborns those with a PI <2.4. In our population, 12.55% of newborns were asymmetric. The prevalence of malformations was significantly higher in the group of asymmetric newborns .Figure We also expressed the relationship between the above variables and malformations as the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each variable, considered as an indicator of the presence of malformations. Table rd percentile), where, predictably, specificity was higher, but sensitivity was very low.Smoking during pregnancy and diseases in pregnancy had no significant association with malformations and low sensitivity-specificity values. More interestingly, the condition of SGA behaved approximately in the same way, and was not a good predictor of malformations. Similar results were also observed for the condition of extreme SGA , and we observed discrete values of sensitivity (29.41%) without losing too much in specificity (88.19%). PPV and NPV also confirmed this trend.Finally, we evaluated the predictive value of the association of the SGA condition with low PI, considering both their intersection and their union (AND and OR). Significant values were obtained only for the union (OR), but using the union of both variables did not improve the results observed for PI alone; sensitivity, predictably, was a little higher, but at the expense of specificity, and the statistical association became weaker (p = 0.007).The analysis in terms of sensitivity and specificity confirmed what could be inferred from the initial analysis: only PI seemed to have some predictive value for the presence of malformations. The other variables considered, including the percentile of weight, were not associated with malformations, or the association was probably too weak to be detected in a limited series of cases. In other words, newborns with low PI seemed to be at higher risk of having malformations, while newborns with low weight percentile at birth  apparently had no increased risk.Finally, Figure SGA newborns are certainly a group whose nature is very heterogeneous, including some absolutely normal babies, “smaller” than the rest of the population for constitutional reasons, and newborns affected by different kinds of disease. Typically, “symmetric” SGA newborns, if pathological, are considered to be affected mainly by genetic, chromosomal and infectious diseases or any other condition affecting the growth of the fetus in the early stages of gestation, while “asymmetric” SGAs are often explained by placental pathologies in late pregnancy.As congenital malformations, or at least some of them, can interfere with normal fetal growth, it is generally assumed that SGA newborns may have a higher prevalence of malformations.In our series, we observed that newborns with birth defects had a weight percentile slightly lower than those in the general population Figure , but theThe prevalence of malformations in the SGA group, however, was definitely comparable to its prevalence in the AGA and LGA groups. Very likely, the small difference in the weight percentile distribution that could be observed between babies with and without malformations is not strong enough to cause a significantly different rate of malformations in the SGA group.We found, however, that PI was a more sensitive marker of malformations. As can be seen in Figure Other epidemiological parameters that we considered, such as smoking in pregnancy and disease in pregnancy, can certainly cause some impairment of fetal growth, but, as might be expected, had no special association with the risk of malformations.In summary, the association between congenital malformations and birth weight seems to be real, but weak, and it is apparent more as an asymmetry of weight versus length than as an absolute reduction in the weight percentile.Particular attention should be given to the detection of malformations at birth, especially those not clinically obvious. Screening procedures may include ultrasonographic evaluation in babies who have a higher risk of malformations.According to our data, a low weight percentile at birth may not be a reliable indicator of such a higher risk. On the contrary, a low PI, as an expression of asymmetric growth, could be considered a more valuable predictor of risk and therefore could be used to select a specific subgroup of newborns which should receive further diagnostic attention.The authors declare that they have no competing interests.GP made substantial contributions to conception and design of the study, and to analysis and interpretation of data, was involved in drafting the manuscript and revising it, and gave final approval of the version to be published. MG made substantial contributions to acquisition of data, was involved in drafting the manuscript, and gave final approval of the version to be published. MP made substantial contributions to acquisition of data, was involved in drafting the manuscript, and gave final approval of the version to be published. EP made substantial contributions to acquisition of data, was involved in drafting the manuscript, and gave final approval of the version to be published. GR made substantial contributions to the design of the study, to acquisition of data and to analysis and interpretation of data, was involved in drafting the manuscript, and gave final approval of the version to be published. GC made substantial contributions to conception and design of the study, was involved in drafting the manuscript and revising it critically for important intellectual content, and gave final approval of the version to be published. All authors read and approved the final manuscript.


Low birth weight is one of the most important public health issues in developing and developed countries and identifying its etiology is important for prevention.Considering the unknown impact of physical activity on low birth weight, this research was conducted to investigate the relationship between physical activity and low birth weight.This research was conducted using a case-control design. The control group was made of 500 women with normal birth weight infants and the case group included 250 women with low birth weight infants from the selected hospitals in city of Tehran. The information was gathered using a researcher-made questionnaire which was prepared for determining the relationship between mothers’ lifestyle during pregnancy and infants' low birth weight using social determinants of health approach. In this questionnaire, scope of physical activity was investigated in three groups of athletic activities, activities at home and leisure activities. Activity intensity was determined using MET scale and the data were analyzed in SPSS software using independent t-test, Chi-square and logistic regression.In the present research, based on the results of multiple logistic regression test, an increase in the time spent on sport activities (OR = 2.20) and home activities (OR =1.44) (P = 0.003) was accompanied by increased chance of giving birth to low birth weight infants; in contrast, one hour increase of leisure activities decreased the probability of low birth weight infants by 0.32 (P = 0.008).An increase in the time spent on sport and home activities, even after considering other influential factors, was related to low birth weight. Low birth weight is one of the most important public health issues in both developing and developed countries. It is one of the determining factors of survival and future physical and mental development of every infant. In fact, it is the most important, simple, common, sensitive and reliable health index used for evaluating health status of infants, hence the status of individuals and society in each country, 2. Low Different factors may be related to low birth weight. According to some researchers, it may be caused by several factors including mothers' low weight at the beginning of pregnancy, mothers' short stature and illnesses like hypertension or genital infections. Many health indexes such as children’s death have improved in the recent two decades due to many efforts for controlling these biological elements, but the prevalence of low birth weight has still remained the same or even has increased in some countries. This poAccording to the WHO, physical activity is defined as any bodily movement of skeletal muscles which leads to energy consumption. Some stThe present work is a part of a large study titled "designing measuring tool and relationship pattern of mothers’ lifestyle during pregnancy and low birth weight", conducted in two steps.This case-control study was conducted in Tehran (IRAN) in 2012. The data collection tool of the study was a researcher-made questionnaire, designed for measuring lifestyle with the approach of social determinants of health. For psychometrics of the questionnaire, face and content validities , criterion validity by criterion tool and consFor this case-control study, first, city of Tehran was divided to five geographical zones of north, south, east, west and center. Then, out of the hospitals in every zone that had maternity ward, some clusters including one or two governmental or social security hospitals were selected according to their delivery rates. To determine the required sample size, after reviewing the literature, considering 10% prevalence for low birth weight, and calculating the research variables, the number of items in the measurement tool and key concepts, were determined as 3 to 10 samples for each variable . Accordi15-45-year-old Iranians at gestational age of 37-42 weeks based on the first day of their last menstruation period (LMP) or Sonography, who went to the selected hospitals for delivery.Lack of problems like multiple pregnancy, cardiovascular diseases, diabetes, renal diseases, thyroid disorders, pulmonary diseases, autoimmune disorders, Pre-eclampsia, placental abruption, premature rupture of membranes, hepatitis, AIDS and other problems; not using special drugs which affect birth weight during pregnancy.Willing to participate in the researchBirth weight of more or less than 2500 g with no known medical problems like congenital abnormalities, cardiac or pulmonary diseases and so on. After obtaining permission from university and hospital authorities, we presented the required information to the study population and convinced them to cooperate. Then the questionnaire was filled out by a team of trained people. The questionnaire was filled out in the following way: first, the questioner or researcher selected the mothers with inclusion criteria in the delivery room and monitored them until delivery. At the time of delivery, the researcher or questioner went to the delivery room, and immediately after delivery, if the infant had no medical problems like congenital disorders, cardiac-pulmonary diseases, etc., and its weight was below 2500 g using the scale in the delivery room, it was placed in the case group. If it weighed between 2500 and 4500 g, it was placed in the control group . Measurement accuracy of all scales in delivery rooms was measured by the researcher as follows: in order to determine scale reliability, a standard weight (control weight of 100 g) was used to control and calibrate the scale after every 10 samples. After transferring the mother to the general care unit and in case she was in good conditions and willing to participate in the study, she was asked to fill out a consent letter. Then, the part of questions related to the patient’s file including laboratory test results, ultrasound examination and so on was completed by the researcher by checking mother’s medical file. Another part which included demographic questions and those related to lifestyle were filled out by interviewing the mother. In this part, information of other important factors which affect low weight including socio-economic status , pregnancy variables  and mother’s health status  was gathered and recorded in the results.Based on MET scale, physical activity may be defined in terms of time, amount and intensity. Hence, to calculate time duration of physical activities of mothers during pregnancy, the time spent on each activity (according to mothers report) was calculated in terms of hours per week and then, For measuring intensity of activities according to MET scale, MET value of each activity (based on MET table) was multIn this study, the two groups (500 control pregnant women with 2500-4500 g infants and 250 case women with infants weighing less than 2500 g) had no significant difference in terms of mean of age, BMI, pregnancy age, pregnancy intervals and family income. But, mothers’ mean of weight increase during pregnancy was significantly different in the two groups (P = 0.002). Mean of birth weight in two groups, case and control, respectively were 2.183 ± 4.24 and 3.243 ± 3.76 and between them according sex weren’t significantly different . In evaluating educational level, chance of delivering low birth weight infant in illiterate mothers was three times as much as that in educated mothers . Husbands’ occupation and mothers’ employment were among other factors which were related to infants' low birth weight in that if the husband was unemployed, chance of this outcome was 4.5 times higher . Also, mothers' employment increased chance of delivering infants with low birth weight by 5.4 times . In this investigation, in terms of time spent on physical activity (week/hour), the mean time spent on doing physical activity at home and leisure was significantly different, in that in the control group, the time spent on physical activity at home was less than that of the case group (18.97 vs. 22.42), but time of doing leisure physical activity was more in the control group than in the case group (8.06 vs. 6.32) (P = 0.038 and 0.003). These results showed a direct relationship between the time spent on physical activity at home and an inverse relationship between the times spent on leisure physical activity on the one hand and low birth weight on the other. There was no significant relationship between mean time of physical activity along with total physical activity and birth weight in the two groups. In terms of mean level of their physical activity based on MET, no significant difference was observed between the amount of physical activity in the two groups, but there was a significant difference between physical activity at home, leisure physical activity and total amount of their physical activity . As far as intensity was concerned, mean time of activity using 3-6 MET scale did not show any difference between the two groups; however, mean time of physical activity with light intensity (P = 0.002) in the case group and sedentary (P = 0.040) in the control group was significantly higher . Variables which affected low birth weight based on independent t-test were entered into the multiple regression model. The results of multiple regression model in terms of the effect of above variables on low birth weight are presented in The present study showed that mean time spent on exercise and home physical activities was in direct relationship with chance of low birth weight so that increasing the time spent on the mentioned activities led to increased chance of delivering a low birth weight infant. In developing countries, women are responsible for house chores and babysitting in addition to outdoor work and are thus exposed to undesirable pregnancy complications such as low birth weight. The impIn this study, leisure physical activity was found to have a protective effect on birth weight. This finding concurs with the results of many studies such as Domingues and Barros and of Takito et al., who referred to a positive protective relationship between leisure physical activity and birth weight. It seemIn this study the correlation between BP and low birth weight was significant. High Blood pressure can Be dangerous for both Mather and the fétus. Women with pre-existing, or chronic, high blood pressure are more likely to have certain complications during pregnancy than those with normal blood pressure. However, some women develop High Blood pressure while they are pregnant and due some adverse outcome such as low birth weight, preterm birth, Intrauterine Growth restriction (IUGR), Intrauterine Fetal Death (IUFD). This finding concurs with the results of some studies , 29. VarIn logistic regression test, occupation was found to have a négatives effect on birth weight. This finding concurs with the results of the study of Needhammer et al. (2009) it was found that more than 40 hours of work per week and shift work increase risks of low birth weight incidence, small for gestational age (SGA), and preterm labor. They also found that part-time work can be a preventative factor for preterm labor . AnotherIn this study, mothers were interviewed shortly after delivery; thus, there is the possibility of their frustration after delivery or pregnancy result might have an influence on their responses. Also, the researches only studied the variables that had the possibility of investigation via interviewing with mothers. There might have been other elements as well which affect birth weight but have not been taken into consideration in this study. So, other studies should be done in this field considering the mentioned conditions. The findings showed that increased athletic physical activities and home activities are directly related to low birth weight, even after considering other effective confounding factors. Therefore, holding preventive educational programs like consulting classes for mothers and their spouses for teaching appropriate physical activities in this period and also spouses’ cooperation in house chores could be very helpful.


We compared the birth weight of newborns born to foreign-born mothers (FBMs) and Taiwan-born mothers (TBMs), using data from the 2005–2006 Taiwan Birth Registry of singleton live births.The Wilcox–Russell method, data restriction, and multiple linear regression were used to analyze the data. The rates of low birth weight (<2500 g) with 95% confidence intervals were computed for TBMs, and for each of the nationalities of FBMs.The mean birth weight of newborns of FBMs was 3157 g, which was higher than that of newborns of TBMs (3109 g). On analysis using the Wilcox–Russell method, both the rate and residual proportion of low-birth-weight (LBW) births were lower among newborns of FBMs  than among newborns of TBMs . After adjusting for sex, mode of delivery, maternal age, smoking status, predisposing maternal risk factors, and condition during pregnancy, the newborns of FBMs weighed 72.9 g  more than the newborns of TBMs. When data were restricted to mothers without any adverse conditions and adjusted for maternal age, the differences in birth weight between the 2 groups remained unchanged. The rates of LBW deliveries among FBMs in Taiwan were significantly lower than those in their respective countries of origin.In Taiwan, newborns of FBMs had a higher birth weight than those of TBMs, even after accounting for potential confounding factors, and had lower rates of LBW deliveries than did mothers in their respective countries of origin. In Taiwan, transnational marriages accounted for 20% of registered marriages in 2005.11 The main purpose of transnational marriages is to continue the bloodline of the family and to ensure management of household affairs.12 The Taiwanese men in transnational marriages are frequently of low socioeconomic status; some are physically or mentally handicapped.11,12 The foreign-born women often become pregnant or give birth shortly after immigrating to Taiwan, even though they may still be adjusting to their new environments.11–13 Therefore, it is reasonable to speculate that babies of FBMs start with disadvantages.Typically, transnational marriages in Taiwan are arrangements made by marriage brokers and frequently involve a Taiwanese man and a woman from Southeast Asia or mainland China.14 NHIT provides 10 free visits for prenatal care and labor.15 Regardless of the socioeconomic status of the family, the health care of the mothers and newborns during pregnancy and delivery is subsidized by the NHIT.The National Health Insurance in Taiwan (NHIT) provides subsidized prenatal care to individuals in all socioeconomic classes. The percentage of the population covered by the NHIT increased from 89.5% in 1995, when NHIT was founded, to 99% in 2004.15 Hence, physicians or midwives are able to document the health status of the expectant mother from the beginning to the end of the pregnancy when they report the birth to the local health office.16The Taiwan Birth Registry contains information on obstetrical diseases and the medical histories of expectant mothers, which allows us to compare the difference in birth weight between 2 birth groups with respect to predisposing conditions or the circumstances of the pregnancy. Unless the fetus suffers serious health problems during pregnancy, most expectant mothers will have prenatal care and give birth at the same medical facility.17 were also investigated.To address the birth weight paradox, we compared the birth weight of 2 groups of mothers (FBMs vs. TBMs), using data from the Taiwan Birth Registry for 2005–2006. The Wilcox–Russell method, restriction, and multiple linear regressions were used for data analysis. The LBW rates for TBMs and FBMs, in Taiwan and in their respective native countries,18). Because there were only small numbers of babies born to mothers from developed countries—including Japan, Korea, South Africa, England, and USA—their records were excluded.Birth data were obtained from the 2005–2006 Taiwan Birth Registry, Bureau of Health Promotion, Department of Health, Taiwan. The Institutional Review Board of the Bureau of Health Promotion, Department of Health, Taiwan approved this study. Only singleton live births with a gestational age of at least 24 weeks were included in the study because induced abortion is legal in Taiwan before 24 weeks of gestational age and because the fetus has a better chance of survival outside the uterus after 24 weeks of gestation. We excluded records of birth weights that were aberrant for gestational age, as determined by expert clinical opinion and statistical analysis Newborn: sex, gestational age, birth weight, date and time of birth, plurality , health problems of the newborn, live birth or stillbirth.(2)Demographic characteristics of parents: maternal and paternal nationality, dates of birth of the mother and father.(3)Delivery: location of the delivery center, who delivered the baby (physician or midwife), and mode of delivery.(4)Conditions during pregnancy: gestational hypertension, gestational diabetes, toxemia of pregnancy, cervical incompetence, polyhydramnios (amniotic fluid index (AFI) >24 cm or deepest amniotic fluid pool (DP) >8 cm) or oligohydramnios (AFI <5 cm or DP <1 cm).(5)Predisposing maternal factors: anemia (hematocrit <30 or hemoglobin <10), history of preterm delivery  or LBW baby (birth weight <2500 g), thalassemia, diabetes mellitus, cardiac disease, chronic hypertension, history of high-birth-weight delivery (birth weight >4000 g), syphilis, pulmonary disease, nephropathy, and rhesus isoimmunization.(6)Adverse maternal behavior: cigarette smoking, alcohol drinking, and illicit drug use during pregnancy.t test were used to compare categorical and continuous data on maternal characteristics, univariately when appropriate. For birth weight, we used the method of Wilcox and Russell,8,9 which involves estimating the predominant normal birth weight distribution and the left-skewed residual percentage of small preterm babies in the distribution of birth weight. The predominant distribution closely corresponds to the birth weight distribution of term births (≥37 completed weeks of gestation). Wilcox and Russell8,9 demonstrated that in any large data set the empirical distribution of term births alone is almost purely normal, with a mean and standard deviation closely approximated by the predominant distribution of all births. However, the residual distribution comprises all births in the lower tail of the curve that fall outside the predominant distribution. In a typical population, 2% to 5% of births are in this residual distribution. Wilcox and Russell also maintained that virtually all births in the residual distribution are preterm births, but that not all preterm births are in the residual distribution.The chi-square test and independent Next, we followed a sequential modeling strategy, using a linear regression procedure, based on all eligible records, and restricted the data to include only mothers without any maternal adverse conditions. Regression models were stratified by nationality. Combined models were then examined for changes in mean birth weight between FBMs and TBMs, after adjusting for important maternal risk factors. LBW rates (%) with 95% confidence intervals (CI) were computed to enable international comparisons. The significance level of this study was 0.05. All analyses were performed using Statistical Analysis Software (SAS) version 9.1.There were 416 335 records in the 2005–2006 Taiwan Birth Registry. After excluding stillbirths (1.1%), non-singleton births (2.8%), gestational age of infants less than 24 weeks (0.6%), FBMs from developed countries (0.3%), and implausible birth weights for gestational age (0.6%), 399 551 records remained for analysis. A total of 50 049 (12.5%) were newborns of FBMs.The newborns of FBMs were heavier mean, 3157 g) than those of TBMs . The LBW rate among newborns of FBMs (4.1%) was significantly lower than among newborns of TBMs (5.9%). Male newborns were heavier than female newborns. Using the Wilcox–Russell method, the mean birth weight of the predominant distribution was 3181 g for newborns of FBMs and 3155 g for newborns of TBMs. The residual proportion was lower among the newborns of FBMs (1.1%) than among the newborns of TBMs (1.7%).  was seen for TBMs who smoked cigarettes as compared to TBMs who did not smoke. With respect to syphilis status, a lower birth weight was seen in newborns whose mothers had syphilis as compared to newborns whose mothers did not have syphilis in FBMs alone, and in FBMs and TBMs combined. More importantly, the newborns of FBMs weighed 72.9 g  more than the newborns of TBMs, after adjustment for predisposing maternal risk factors, conditions during pregnancy, newborn’s sex, mode of delivery, maternal age, cigarette smoking, and syphilis. When data were restricted to mothers without any adverse conditions, and adjusted for newborn’s sex, mode of delivery, and maternal age, the difference in birth weight between the 2 groups remained unchanged  of FBMs in Taiwan were also significantly lower than those of mothers in their countries of origin.19 However, this notion was contradicted by the findings of a study by David et al,2 which compared the distribution of birth weights among newborns of African-born black women, US-born white women, and US-born black women. They found that the birth weight distributions of newborns of African-born black women and US-born white women were similar but much higher than the birth weight distribution of the newborns of US-born black women. They concluded that genetic factors were unlikely to explain the difference in birth weight between foreign-born mothers and native-born mothers in the US population. In a study of births in Portugal, the mean birth weight of newborns of foreign-born African women was highest (3317 g), followed by newborns of Portuguese white mothers (3280 g) and newborns of Portuguese-born African mothers (3248 g).4 Guendelman et al reported that the newborns of Mexican-born and North African-born women residing in the United States, France, and Belgium had higher birth weights than newborns of native-born women of the same respective ethnic groups.3 In our study, we observed that the mean birth weight among newborns of FBMs was higher than that among newborns of TBMs. Also, the rates of LBW were lower among newborns of FBMs than among newborns in the mothers’ respective countries of origin. Based on a comparison of the birth weight of newborns of foreign-born and native-born women of the same ethnic group in the US, Portugal, France, Belgium, and Asia (this study), genetic factors appear unlikely to explain the paradox of birth weight. However, it should be pointed out that genetic information on the fetus is usually not available in data from the national birth registry or birth certificates. Further study may clarify the role of genetic factors on birth weight.The hypothesis that differences in birth weight resulted from genetic dissimilarities due to race was the first attempt to explain the observed differences.20 In our study, the low rate of medical complications during pregnancy  may have resulted from under-reporting and could bring our findings into question. Because FBMs and TBMs had the same number of prenatal visits due to health coverage by the NHIT,21 nondifferential misclassification of maternal exposure was expected. Because nondifferential misclassification introduces a bias toward the null value,22 a significant nonzero effect of maternal nationality on birth weight in our study suggests the possibility of an even stronger effect of maternal nationality on birth weight. After adjusting the data for adverse maternal conditions on multiple linear models, or restricting the data to mothers without any adverse factors, the birth weight in newborns of FBMs remained higher than that of newborns born to TBMs. We conclude that predisposing maternal factors and conditions during pregnancy do not explain the difference in the birth weights of the newborns.Conditions during pregnancy and predisposing maternal factors can affect the birth weight of newborns.23 In our study, birth weight increased with maternal age among the 2 maternal groups, with or without consideration of adverse maternal conditions. Moreover, we observed that the effect of maternal age on mean birth weight differed between foreign-born and Taiwan-born mothers: the effects of age were greater for the FBMs. In general, Taiwanese teenagers are students, which is not the case for FBMs. It is possible that teenaged TBMs delayed their utilization of prenatal care due either to a failure to recognize the symptoms of pregnancy, denial of the pregnancy, fear of their parents’ response to the pregnancy, lack of financial resources,24 conflict with school enrollment,25 or significant substance abuse.26 Delay in prenatal care among teenaged mothers might therefore account for the lower birth weight among TBMs. For the mothers aged over 40 years, parity may partially explain the differences in birth weight between the 2 birth groups. Unfortunately, parity is not recorded in the Taiwan Birth Registry. Many studies reported that birth weight is higher among women of higher parity.27 Prior study has revealed a marked increase in the fertility rate among FBMs aged between 15 and 29, whereas TBMs typically have children later in life.28 Moreover, because the marriage age for women in Taiwan is increasing,29 they may be having their first babies later in life. Hence, it is possible that the parity of TBMs aged over 40 years was lower than that of FBMs.The relation between maternal age and birth weight is well-known.4,30,31 The rate of cigarette smoking among FBMs in Taiwan (0.01%) was lower than rates reported among foreign-born mothers in other countries .5 In addition, we observed extremely low rates of illicit drug use and alcohol drinking among FBMs in our study. The effects of healthy behaviors that women bring from their countries of origin have been reported.32 The low rates of use of addictive substances such as tobacco, alcohol, and illicit drugs among FBMs support the hypothesis that behavioral risk factors contribute to the birth weight advantage of newborns of FBMs.32Maternal cigarette smoking has been consistently associated with reduced birth weight among a wide range of populations.33 The effect of maternal syphilis on birth weight was −87.3 g . Although the maternal syphilis rate for FBMs (0.15%) was higher than that for TBMs (0.03%), the rates for both groups were much lower than those found in most underdeveloped countries.33–35 The maternal syphilis rates for FBMs were lower than those in their respective countries of origin. Prenatal treatment of maternal syphilis among FBMs, or the presence of a selection effect , may explain the low rate of maternal syphilis in our study.However, not all the conditions for FBMs are favorable. In this study, FBMs were more likely to have had syphilis than were TBMs. Maternal syphilis has been associated with a high risk of adverse pregnancy outcomes.36 In Taiwan, Hung et al showed that FBMs have the same numbers of prenatal visits as TBMs.21 Hence, the free prenatal care service provided by the NHIT may contribute to the higher birth weight of newborns of FBMs, as compared to the birth weights in their respective countries of origin , parents are responsible for reporting the birth to the office of Residency Administration. The community head and a police officer of the magistracy together complete the form of the birth investigation certificate after an inquiry on the birth. The newborn’s family will then take this birth investigation certificate to complete the process of birth registration. This comprehensive system of birth registration has been in place for many years. Therefore, we believe that there are few missing data in the Taiwan Birth Registry.10 One possibility is that TBMs gave births several years after marriage28 and/or gave birth to more children than did FBMs. This requires further investigation.It is unclear why the proportion of babies born to FBMs (12.5%) differed from the percentage of transnational marriages (20%).36 maternal size,40 parental education,5 socioeconomic status,41 social support,42 occupational stress,43 and nutrition.44 Second, although a large proportion of FBMs came to Taiwan via marriage trade, some did not. Third, a small portion of newborns in TBMs may be from second-generation transnational marriages because translational marriage in Taiwan became common after 1987.The present research possesses several limitations due to the absence of important data, which are not collected for the Taiwan Birth Registry. These include data related to birth weight, including prenatal care,