human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Maternal smoking during early pregnancy is associated with a reduced risk for preeclampsia even after smoking cessation during pregnancy . Although the pathophysiology of preeclampsia has not been established , placental growth factor ( PlGF ) is believed to be a key factor . The aim of this study was to assess the effect of maternal smoking on the PlGF expression in invasive trophoblasts at early gestation . We collected villous tissues from women requesting surgical termination due to non-medical reasons at 7 - 8 weeks of gestation . The maternal smoking status was evaluated by measuring the serum cotinine level and patients were divided into two groups : active smokers and non-smokers . After separating invasive trophoblasts from villous tissues cultured initially under 2 % O2 for 24 hours , the separated invasive trophoblasts were cultured under 2 % or 8 % O2 for 48 hours . The expression levels of the PlGF gene in villous tissue specimens and in invasive trophoblasts cultured after the conditions were quantified using qRT-PCR . The levels of PlGF protein in the medium were quantified using an ELISA . The gene expression level of PlGF in the villi in the active-smokers was significantly higher than that of the non-smokers . In comparison of the invasive trophoblasts under normoxia and oxygenated conditions , the ratio of PlGF gene expression and protein expression under oxygenation ( 2 % O2 + 8 % O2 / 2 % O2 + 2 % O2 ) in the active-smokers were both significantly higher than in the non-smokers . Maternal smoking history appears to stimulate PlGF expression in invasive trophoblasts under oxygenated conditions . This may be one of several causes leading to the protective effect of maternal smoking on preeclampsia Background Maternal overweight , obesity , and gestational diabetes ( GD ) have been negatively associated with offspring development . Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted . Methods In an observational cohort study we included 331 pregnant women from Granada , Spain . The mothers were categorized into four groups according to BMI and their GD status ; overweight ( n:56 ) , obese ( n:64 ) , GD ( n:79 ) , and healthy normal weight controls ( n:132 ) . We assessed maternal growth and nutritional biomarkers  at 24 weeks ( n = 269 ) , 34 weeks ( n = 310 ) and at delivery ( n = 310 ) and the perinatal characteristics including cord blood biomarkers . Results Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight , waist circumference , and placental weight were higher in the obese group , including a significantly increased prevalence of macrosomia . Except for differences in markers of glucose metabolism ( glucose , HbA1c , insulin and uric acid ) we found at some measures that overweight and /or obese mothers had lower levels of transferrin saturation , hemoglobin , Vitamin B12 and folate and higher levels of C-reactive protein , erythrocyte sedimentation rate , ferritin , and cortisol .  GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate . The latter was seen also in cord blood . Conclusions We identified several metabolic alterations in overweight , obese and GD mothers compared to controls . Together with the observed differences in infant anthropometrics , these may be important biomarkers in future research regarding the programming of health and disease in children . Trial registration The trial was registered at clinical trials.gov , identifier ( NCT01634464 ) The aim of this study was to test whether or not adaptations in partial , total and specific oxygen diffusive conductances occur in the placentae of women who smoke cigarettes during pregnancy and help to compensate for intrauterine fetal hypoxic stress . Tissue sections were r and omly sample d from human term placentae divided into two groups ( non-smokers and smokers ) according to maternal smoking status . In smokers , status was expressed as either declared smoking rate or level of plasma cotinine ( the major metabolite of nicotine ) . Sections were analysed stereologically to estimate key structural quantities ( vascular volumes , exchange surface areas , tissue diffusion distances ) . These were combined with previously-published physicochemical quantities ( oxygen-haemoglobin reaction rates and tissue oxygen diffusion coefficients ) in order to estimate the partial conductances of six tissue compartments of the oxygen pathway : maternal erythrocytes and plasma , villous trophoblast , villous stroma ( including fetal capillary wall ) , fetal plasma and erythrocytes . From partial conductances and birthweights , total and specific conductances were calculated for each placenta . Results were assessed statistically by analyses of variance and t -tests . Despite apparent improvements in the partial conductances of the maternal erythrocytes and plasma , total and specific conductances did not alter significantly in smoking groups . However , the relative biases affecting these estimates may be different in smokers and non-smokers . We conclude that total conductance does not increase in placentae associated with maternal smoking . However , given that the fetus suffers chronic hypoxic stress as a consequence of smoking ( evidence d here by elevated haematocrits ) , even a constant diffusive conductance implies a reduced transplacental partial pressure gradient . This could be a contributory factor to the reduced birthweight BACKGROUND We conducted an epigenome-wide association study ( EWAS ) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight .  METHODS DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente ( INMA ) birth cohort .  Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy . We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort . We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two- sample Mendelian r and omization approach . RESULTS Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [ false discovery rate ( FDR ) < 0.05 ] . We vali date d and replicated differential methylation at three top-ranking loci : cg27402634 located between LINC00086 and LEKR1 , a gene previously related to birthweight in genome-wide association studies ; cg20340720 ( WBP1L ) ; and cg25585967 and cg12294026 ( TRIO ) . Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed . Differential methylation at cg27402634 explained up to 36 % of the lower birthweight in the offspring of smokers ( Sobel P-value < 0.05 ) . A two- sample Mendelian r and omization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight . CONCLUSIONS We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy . Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome The fetal origins theory of adult disease suggests that term infants who are small for their gestational age have an increased susceptibility to chronic disease in adulthood as a consequence of physiologic adaptations to undernutrition during fetal life . Consistent evidence for an influence of women 's dietary composition during pregnancy on growth of their babies is lacking , despite robust effects in animal experiments . We undertook a prospect i ve observational study of 557 women aged 18 - 41 y , living in Adelaide , South Australia .  Diet was assessed in early and late pregnancy using an FFQ . In early pregnancy , medians for energy intake , the proportion of energy derived from protein and from carbohydrate were 9.0 MJ , 17 and 48 % , respectively . In late pregnancy the corresponding medians were 9.2 MJ , 16 and 49 % . In early pregnancy , the percentage of energy derived from protein was positively associated with birth weight ( P = 0.02 ) and placental weight ( P = 0.07 ) , independently of energy intake and weight gain during pregnancy , and after adjustment for potential confounders , including maternal age , parity , and smoking . Effects were stronger among women ( n = 429 ) who had reliable data , based on prespecified criteria including the plausibility of dietary data when referenced against estimated energy expenditure . In addition , for this subgroup , the percentage of energy from carbohydrate in early and late pregnancy was negatively associated with ponderal index of the baby , and a specific effect of protein from dairy sources was identified . These data support the proposition that maternal dietary composition has an effect on fetal growth . Maternal diet in Western societies may therefore be important for the long-term health of the child BACKGROUND The role played by dairy product intake during pregnancy on neonatal outcomes has raised interest in the last few years . However , studies on this association remain scarce . Thus , the aim of this study was to determine the association between dairy product consumption during pregnancy and neonatal and maternal outcomes . METHODS A prospect i ve study was conducted with 98 pregnant women , aged 18 - 40 , from the city of Porto , Portugal . Socio-demographic and lifestyle characteristics were assessed through a question naire . Dairy product consumption was assessed with a three-day food diary completed during the first and second trimesters . Postpartum medical records were examined for neonatal and maternal outcomes . Multivariate linear regression analyses were performed to assess the association between dairy intake and neonatal and maternal outcomes , adjusting for dietary variables and maternal characteristics . RESULTS Compared to the first trimester pregnant women had higher energy intake and lower calcium , iodine and yogurt intake in the second trimester ( P<0.05 ) . Total dairy and yogurt intake in the first trimester were positively associated with head circumference and placental weight ( respectively β=0.002 , P=0.014 , β=0.333 , P=0.012 ) . Change in total dairy intake between the second and first trimester was negatively associated with maternal weight gain during pregnancy ( β=-0.007 , P=0.020 ) . CONCLUSION The findings of this study suggest that dairy product intake during pregnancy may have an effect on neonatal head circumference , placental weight , and gestational weight gain OBJECTIVE A sFlt-1/PlGF ratio of ≤38 has been reported to predict the absence of preeclampsia ( PE ) in singleton pregnancies . We evaluated whether a sFlt-1/PlGF ratio of ≤38 could be used to predict the absence of PE  in twin pregnancies and maternal and fetal/neonatal complications . METHODS This is a secondary analysis of a prospect i ve multicenter cohort study that enrolled women with suspected or confirmed PE with the aim of evaluating the use of the sFlt-1 , PlGF and their ratio to predict maternal and fetal/neonatal complications . Twin and singleton pregnancies with clinical ly suspected or confirmed PE were matched for gestational age and parity . Blood sample s were drawn at time of study entry , but serum values of sFlt-1 and PlGF and their ratio were determined postpartum . RESULTS Twenty-one women with twin and 21 with singleton gestations were included at a median gestational age of 30 weeks . At inclusion PE was diagnosed in 13 twin and 15 singleton pregnancies . In comparison to singleton control pregnancies , twin controls had a significantly higher sFlt-1 ( 6377 vs. 1732 pg/ml , p = 0.008 ) , a higher sFlt-1/PlGF ratio 26 vs. 3 p = 0.361 ) and a lower PlGF ( 228 vs. 440 pg/ml p = 0.479 ) . Compared to singleton preeclamptic pregnancies values of sFlt-1 ( 9134 vs. 8625 pg/ml ) did not differ , whereas values of PlGF ( 185 vs. 33 pg/ml , p < 0.001 ) were higher and values of the ratio ( 49 vs. 158 , p = 0.002 ) were lower in preeclamptic twin pregnancies . All preeclamptic patients with a singleton pregnancy had a ratio > 38 , but only 5 of the 13 patients with a preeclamptic twin pregnancy . Conversely , the ratio was ≤38 in 5 of the 6 control singleton , but in only 4 of the 8 control twin pregnancies . When classified according to a ratio ≤38 or > 38 at inclusion , maternal complications occurred more frequently in patients with a ratio > 38 both in singleton and twin pregnancies . In singleton pregnancies fetal/neonatal complications , except one admission to NICU , only occurred in patients with a ratio > 38 . In twin pregnancies fetal/neonatal complications occurred equally frequent in women with a ratio ≤38 or > 38 . CONCLUS 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Maternal smoking during early pregnancy is associated with a reduced risk for preeclampsia even after smoking cessation during pregnancy . Although the pathophysiology of preeclampsia has not been established , placental growth factor ( PlGF ) is believed to be a key factor . The aim of this study was to assess the effect of maternal smoking on the PlGF expression in invasive trophoblasts at early gestation . We collected villous tissues from women requesting surgical termination due to non-medical reasons at 7 - 8 weeks of gestation . The maternal smoking status was evaluated by measuring the serum cotinine level and patients were divided into two groups : active smokers and non-smokers . After separating invasive trophoblasts from villous tissues cultured initially under 2 % O2 for 24 hours , the separated invasive trophoblasts were cultured under 2 % or 8 % O2 for 48 hours . The expression levels of the PlGF gene in villous tissue specimens and in invasive trophoblasts cultured after the conditions were quantified using qRT-PCR . The levels of PlGF protein in the medium were quantified using an ELISA . The gene expression level of PlGF in the villi in the active-smokers was significantly higher than that of the non-smokers . In comparison of the invasive trophoblasts under normoxia and oxygenated conditions , the ratio of PlGF gene expression and protein expression under oxygenation ( 2 % O2 + 8 % O2 / 2 % O2 + 2 % O2 ) in the active-smokers were both significantly higher than in the non-smokers . Maternal smoking history appears to stimulate PlGF expression in invasive trophoblasts under oxygenated conditions . This may be one of several causes leading to the protective effect of maternal smoking on preeclampsia Background Maternal overweight , obesity , and gestational diabetes ( GD ) have been negatively associated with offspring development . Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted . Methods In an observational cohort study we included 331 pregnant women from Granada , Spain . The mothers were categorized into four groups according to BMI and their GD status ; overweight ( n:56 ) , obese ( n:64 ) , GD ( n:79 ) , and healthy normal weight controls ( n:132 ) . We assessed maternal growth and nutritional biomarkers  at 24 weeks ( n = 269 ) , 34 weeks ( n = 310 ) and at delivery ( n = 310 ) and the perinatal characteristics including cord blood biomarkers . Results Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight , waist circumference , and placental weight were higher in the obese group , including a significantly increased prevalence of macrosomia . Except for differences in markers of glucose metabolism ( glucose , HbA1c , insulin and uric acid ) we found at some measures that overweight and /or obese mothers had lower levels of transferrin saturation , hemoglobin , Vitamin B12 and folate and higher levels of C-reactive protein , erythrocyte sedimentation rate , ferritin , and cortisol .  GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate . The latter was seen also in cord blood . Conclusions We identified several metabolic alterations in overweight , obese and GD mothers compared to controls . Together with the observed differences in infant anthropometrics , these may be important biomarkers in future research regarding the programming of health and disease in children . Trial registration The trial was registered at clinical trials.gov , identifier ( NCT01634464 ) The aim of this study was to test whether or not adaptations in partial , total and specific oxygen diffusive conductances occur in the placentae of women who smoke cigarettes during pregnancy and help to compensate for intrauterine fetal hypoxic stress . Tissue sections were r and omly sample d from human term placentae divided into two groups ( non-smokers and smokers ) according to maternal smoking status . In smokers , status was expressed as either declared smoking rate or level of plasma cotinine ( the major metabolite of nicotine ) . Sections were analysed stereologically to estimate key structural quantities ( vascular volumes , exchange surface areas , tissue diffusion distances ) . These were combined with previously-published physicochemical quantities ( oxygen-haemoglobin reaction rates and tissue oxygen diffusion coefficients ) in order to estimate the partial conductances of six tissue compartments of the oxygen pathway : maternal erythrocytes and plasma , villous trophoblast , villous stroma ( including fetal capillary wall ) , fetal plasma and erythrocytes . From partial conductances and birthweights , total and specific conductances were calculated for each placenta . Results were assessed statistically by analyses of variance and t -tests . Despite apparent improvements in the partial conductances of the maternal erythrocytes and plasma , total and specific conductances did not alter significantly in smoking groups . However , the relative biases affecting these estimates may be different in smokers and non-smokers . We conclude that total conductance does not increase in placentae associated with maternal smoking . However , given that the fetus suffers chronic hypoxic stress as a consequence of smoking ( evidence d here by elevated haematocrits ) , even a constant diffusive conductance implies a reduced transplacental partial pressure gradient . This could be a contributory factor to the reduced birthweight BACKGROUND We conducted an epigenome-wide association study ( EWAS ) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight .  METHODS DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente ( INMA ) birth cohort .  Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy . We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort . We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two- sample Mendelian r and omization approach . RESULTS Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [ false discovery rate ( FDR ) < 0.05 ] . We vali date d and replicated differential methylation at three top-ranking loci : cg27402634 located between LINC00086 and LEKR1 , a gene previously related to birthweight in genome-wide association studies ; cg20340720 ( WBP1L ) ; and cg25585967 and cg12294026 ( TRIO ) . Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed . Differential methylation at cg27402634 explained up to 36 % of the lower birthweight in the offspring of smokers ( Sobel P-value < 0.05 ) . A two- sample Mendelian r and omization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight . CONCLUSIONS We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy . Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome The fetal origins theory of adult disease suggests that term infants who are small for their gestational age have an increased susceptibility to chronic disease in adulthood as a consequence of physiologic adaptations to undernutrition during fetal life . Consistent evidence for an influence of women 's dietary composition during pregnancy on growth of their babies is lacking , despite robust effects in animal experiments . We undertook a prospect i ve observational study of 557 women aged 18 - 41 y , living in Adelaide , South Australia .  Diet was assessed in early and late pregnancy using an FFQ . In early pregnancy , medians for energy intake , the proportion of energy derived from protein and from carbohydrate were 9.0 MJ , 17 and 48 % , respectively . In late pregnancy the corresponding medians were 9.2 MJ , 16 and 49 % . In early pregnancy , the percentage of energy derived from protein was positively associated with birth weight ( P = 0.02 ) and placental weight ( P = 0.07 ) , independently of energy intake and weight gain during pregnancy , and after adjustment for potential confounders , including maternal age , parity , and smoking . Effects were stronger among women ( n = 429 ) who had reliable data , based on prespecified criteria including the plausibility of dietary data when referenced against estimated energy expenditure . In addition , for this subgroup , the percentage of energy from carbohydrate in early and late pregnancy was negatively associated with ponderal index of the baby , and a specific effect of protein from dairy sources was identified . These data support the proposition that maternal dietary composition has an effect on fetal growth . Maternal diet in Western societies may therefore be important for the long-term health of the child BACKGROUND The role played by dairy product intake during pregnancy on neonatal outcomes has raised interest in the last few years . However , studies on this association remain scarce . Thus , the aim of this study was to determine the association between dairy product consumption during pregnancy and neonatal and maternal outcomes . METHODS A prospect i ve study was conducted with 98 pregnant women , aged 18 - 40 , from the city of Porto , Portugal . Socio-demographic and lifestyle characteristics were assessed through a question naire . Dairy product consumption was assessed with a three-day food diary completed during the first and second trimesters . Postpartum medical records were examined for neonatal and maternal outcomes . Multivariate linear regression analyses were performed to assess the association between dairy intake and neonatal and maternal outcomes , adjusting for dietary variables and maternal characteristics . RESULTS Compared to the first trimester pregnant women had higher energy intake and lower calcium , iodine and yogurt intake in the second trimester ( P<0.05 ) . Total dairy and yogurt intake in the first trimester were positively associated with head circumference and placental weight ( respectively β=0.002 , P=0.014 , β=0.333 , P=0.012 ) . Change in total dairy intake between the second and first trimester was negatively associated with maternal weight gain during pregnancy ( β=-0.007 , P=0.020 ) . CONCLUSION The findings of this study suggest that dairy product intake during pregnancy may have an effect on neonatal head circumference , placental weight , and gestational weight gain OBJECTIVE A sFlt-1/PlGF ratio of ≤38 has been reported to predict the absence of preeclampsia ( PE ) in singleton pregnancies . We evaluated whether a sFlt-1/PlGF ratio of ≤38 could be used to predict the absence of PE  in twin pregnancies and maternal and fetal/neonatal complications . METHODS This is a secondary analysis of a prospect i ve multicenter cohort study that enrolled women with suspected or confirmed PE with the aim of evaluating the use of the sFlt-1 , PlGF and their ratio to predict maternal and fetal/neonatal complications . Twin and singleton pregnancies with clinical ly suspected or confirmed PE were matched for gestational age and parity . Blood sample s were drawn at time of study entry , but serum values of sFlt-1 and PlGF and their ratio were determined postpartum . RESULTS Twenty-one women with twin and 21 with singleton gestations were included at a median gestational age of 30 weeks . At inclusion PE was diagnosed in 13 twin and 15 singleton pregnancies . In comparison to singleton control pregnancies , twin controls had a significantly higher sFlt-1 ( 6377 vs. 1732 pg/ml , p = 0.008 ) , a higher sFlt-1/PlGF ratio 26 vs. 3 p = 0.361 ) and a lower PlGF ( 228 vs. 440 pg/ml p = 0.479 ) . Compared to singleton preeclamptic pregnancies values of sFlt-1 ( 9134 vs. 8625 pg/ml ) did not differ , whereas values of PlGF ( 185 vs. 33 pg/ml , p < 0.001 ) were higher and values of the ratio ( 49 vs. 158 , p = 0.002 ) were lower in preeclamptic twin pregnancies . All preeclamptic patients with a singleton pregnancy had a ratio > 38 , but only 5 of the 13 patients with a preeclamptic twin pregnancy . Conversely , the ratio was ≤38 in 5 of the 6 control singleton , but in only 4 of the 8 control twin pregnancies . When classified according to a ratio ≤38 or > 38 at inclusion , maternal complications occurred more frequently in patients with a ratio > 38 both in singleton and twin pregnancies . In singleton pregnancies fetal/neonatal complications , except one admission to NICU , only occurred in patients with a ratio > 38 . In twin pregnancies fetal/neonatal complications occurred equally frequent in women with a ratio ≤38 or > 38 . CONCLUS 
    Output:
    