Maternal Smoking History Enhances the Expression of Placental Growth Factor in Invasive Trophoblasts at Early Gestation Despite Cessation of Smoking Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE) Maternal cigarette smoking and oxygen diffusion across the placenta. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy. Dietary composition of pregnant women is related to size of the baby at birth. Relationship between dairy product intake during pregnancy and neonatal and maternal outcomes among Portuguese women. The predictive value of the sFlt-1/PlGF ratio on short-term absence of preeclampsia and maternal and fetal or neonatal complications in twin pregnancies. Early first-trimester trophoblast volume in pregnancies that result in live birth or miscarriage. Maternal prepregnancy obesity is associated with higher risk of placental pathological lesions. The association of body mass index with serum angiogenic markers in normal and abnormal pregnancies. Serum pregnancy-associated plasma protein A levels in the first, second and third trimester of pregnancy: relation to newborn anthropometric parameters and maternal tobacco smoking Maternal dietary patterns and preterm delivery: results from large prospective cohort study Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial1 Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome The Mediterranean diet and fetal size parameters: the Generation R Study. Prenatal parental tobacco smoking, gene specific DNA methylation, and newborns size: the Generation R study Evaluation of the impact of maternal smoking on ultrasound and endocrinological markers of first trimester placentation. The effect of smoking and caffeine on the fetus and placenta in pregnancy. Low midpregnancy placental volume in rural Indian women: A cause for low birth weight? The use of the mHealth program Smarter Pregnancy in preconception care: rationale, study design and data collection of a randomized controlled trial Maternal risk factors for abnormal placental growth: The national collaborative perinatal project Quantitative effects of tobacco smoking exposure on the maternal-fetal circulation Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study. First-Trimester Placental and Myometrial Blood Perfusion Measured by Three-Dimensional Power Doppler in Preeclampsia. Sex specific adaptations in placental biometry of overweight and obese women. Relationship between maternal nutrient intakes in early and late pregnancy and infants weight and proportions at birth: prospective cohort study Maternal obesity and gestational diabetes are associated with placental leptin DNA methylation. Maternal weight and body composition during pregnancy are associated with placental and birth weight in rural Bangladesh. Maternal and infant factors associated with neonatal adiposity: Results from the Tasmanian Infant Health Survey (TIHS) Maternal obesity and its effect on placental cell turnover Placental findings associated with maternal obesity at early pregnancy. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. Periconception maternal characteristics and embryonic growth trajectories: the Rotterdam Predict study. Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers. Longitudinal study of serum placental GH in 455 normal pregnancies: correlation to gestational age, fetal gender, and weight. Determinants of folic acid use in early pregnancy in a multi-ethnic urban population in The Netherlands: the Generation R study.
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 . CONCLUSION Serum sFlt-1 levels are considerably higher in twin than in singleton control gestations . A sFlt-1/PlGF ratio of ≤38 to predict short-term absence of PE is not applicable to  twin pregnancies  in predicting either the absence of PE or the absence of adverse pregnancy outcomes OBJECTIVES To assess the validity of trophoblast volume measurements on three-dimensional ultrasound ( 3D-US ) with Virtual Organ Computer-aided AnaLysis ( VOCAL(TM ) ) , to create reference values between 6 and 12 weeks of gestation and to compare trophoblast volume between pregnancies ending in miscarriage and those result ing in live birth . METHODS In a prospect i ve periconceptional cohort , we performed weekly 3D-US in 112 singleton pregnancies result ing in a non-malformed live birth and in 56 ending in miscarriage . Scans were performed between 6 and 12 weeks . Trophoblast volumes were calculated by subtracting the gestational sac volume from the volume of the total pregnancy . The interobserver and intraobserver agreement of measurements were determined to assess validity . Reference values were created for trophoblast volume in relation to crown-rump length and gestational age . RESULTS A total of 722 3D-US examinations were available for offline VOCAL measurements , but measurements could be performed in only 53 % of these due to non-targeted scanning and incomplete framing . Interobserver and intraobserver agreement for trophoblast volume measurements were excellent , with intraclass correlation coefficients > 0.97 . Trophoblast volumes of pregnancies ending in miscarriage were significantly smaller ( P < 0.01 ) than were those of pregnancies that result ed in live birth . Trophoblast growth in pregnancies ending in miscarriage was also reduced compared with that in pregnancies that result ed in live birth . CONCLUSION VOCAL is a valid technique for measuring trophoblast volume during the early first trimester of pregnancy . Pregnancies ending in miscarriage have smaller trophoblast volumes as well as reduced trophoblast growth compared with those that result in live birth INTRODUCTION Prepregnancy obesity is associated with increased morbidity and mortality for mother and offspring . The objective of our study is to estimate the effect of maternal prepregnancy weight on placental pathological lesions .. METHODS Data used for this study were from the U.S. Collaborative Perinatal Project , a large prospect i ve cohort study . It consisted of 54390 women giving a singleton birth from 1959 to 1966 . More than 84 % of women had both detailed placental pathological examinations and anthropometric measurements .  Logistic regression models were used to test the associations between maternal prepregnancy body mass index ( BMI ) and placental pathological lesions adjusting for potential confounders . Spline smoothing was applied to describe the relation of prepregnancy BMI and placenta weight-to-birthweight ratio . RESULTS The prepregnancy obese women ( BMI ≥ 30 kg/m(2 ) ) showed a higher rate of maternal origin vascular lesions , maternal origin villous lesions , fetal neutrophilic infiltration , and meconium of fetal membrane compared with the normal-weight women ( 18.5 ≤ BMI < 24.9 ) . The odds ratios ranged from 1.18 to 1.97 after adjusting for potential confounders . These higher odds were consistent in prepregnancy obese women without obstetric complications . Furthermore , placenta weight-to-birthweight ratio , the proxy for placenta insufficiency , was positively associated with maternal prepregnancy BMI .. CONCLUSIONS Our study provides evidence that prepregnancy obesity exerts its adverse in-utero influence on placental pathology . These influences may have impact on maternal and fetal health . With obesity rising steadily , these results appear to raise serious public health concerns of prepregnancy obesity OBJECTIVE Because obesity is a risk factor for placental dysfunction , we hypothesized that maternal body mass index ( BMI ) would be associated with alterations in serum angiogenic markers . STUDY DESIGN We included 2399 singleton pregnancies with and without placental dysfunction in a prospect i ve longitudinal cohort study of angiogenic markers . We modeled the relationship between categorical and continuous BMI , soluble fms-like tyrosine kinase-1 ( sFlt-1 )  , and  placental growth factor ( PlGF )  over gestation , stratified by pregnancy outcome . RESULTS In women with normal pregnancies , a higher BMI was associated with lower sFlt-1 values across gestation ( P < .0001 ) , lower PlGF in the second and third trimesters ( P < .0001 ) , and lower rate of change in PlGF ( P < .0001 ) . Similar relationships were seen between maternal BMI , sFlt-1 ( P < .0001 ) , and PlGF ( P = .0005 ) in women with clinical ly evident placental dysfunction . CONCLUSION The sFlt-1 value is inversely associated with maternal BMI . The pattern of change in PlGF is also dependent on maternal BMI , indicating that obese women may have abnormalities in angiogenesis near term Introduction The purpose of this study was to evaluate the associations of the first , second and third trimester serum pregnancy-associated plasma protein A ( PAPP-A ) concentrations with neonatal anthropometric parameters . The effect of tobacco smoking during pregnancy on PAPP-A level was also studied . Material and methods One hundred and fifty healthy pregnant women were divided into smoking and tobacco-abstinent groups .  Serum PAPP-A level  was measured with the KRYPTOR rapid r and om-access immunoassay analyzer . The relationship between PAPP-A and newborn related outcome as well as markers of estimated intensity of cigarette smoking was evaluated by univariate and multivariate linear regression . Results Pregnancy-associated plasma protein A concentration was positively correlated with birth weight in the first ( β = 31.6 ; p < 0.001 ) , second ( β = 10.6 ; p < 0.05 ) , and third ( β = 4.6 ; p < 0.001 ) trimester of gestation . A significant association between PAPP-A and birth body length and head circumference in the second ( β = 0.02 ; p < 0.05 ) and third trimester ( β = 0.01 ; p < 0.01 ) was also found . The serum PAPP-A levels were significantly lower in the smoking than in the tobacco-abstinent group in each trimester of pregnancy ( p < 0.001 ) . The largest impact of the number of cigarettes smoked per day on PAPP-A level was found in the second ( β = –1.2 ; p = 0.004 ) and third trimester ( β = –2.6 ; p = 0.001 ) . Conclusions Maternal serum PAPP-A levels during gestation might be significant predictors for birth weight . Increased PAPP-A concentrations in the second and third trimester appeared to also be predictive for newborn body length and head circumference . Smoking alters maternal PAPP-A levels in all trimesters , with the greatest impact related to the number of cigarettes smoked per day Objective To examine whether an association exists between maternal dietary patterns  and risk of preterm delivery . Design Prospect i ve cohort study . Setting Norway , between 2002 and 2008 . Participants 66 000 pregnant women ( singletons , answered food frequency question naire , no missing information about parity or previously preterm delivery , pregnancy duration between 22 + 0 and 41 + 6 gestational weeks , no diabetes , first enrolment pregnancy ) . Main outcome measure Hazard ratio for preterm delivery according to level of adherence to three distinct dietary patterns interpreted as “ prudent ” ( for example , vegetables , fruits , oils , water as beverage , whole grain cereals , fibre rich bread ) , “ Western ” ( salty and sweet snacks , white bread , desserts , processed meat products ) , and “ traditional ” ( potatoes , fish ) . Results After adjustment for covariates , high scores on the “ prudent ” pattern were associated with significantly reduced risk of preterm delivery hazard ratio for the highest versus the lowest third ( 0.88 , 95 % confidence interval 0.80 to 0.97 ) . The prudent pattern was also associated with a significantly lower risk of late and spontaneous preterm delivery . No independent association with preterm delivery was found for the “ Western ” pattern . The “ traditional ” pattern was associated with reduced risk of preterm delivery for the highest versus the lowest third ( hazard ratio 0.91 , 0.83 to 0.99 ) . Conclusion This study showed that women adhering to a “ prudent ” or a “ traditional ” dietary pattern during pregnancy were at lower risk of preterm delivery compared with other women . Although these findings can not establish causality , they support dietary advice to pregnant women to eat a balanced diet including vegetables , fruit , whole grains , and fish and to drink water . Our results indicate that increasing the intake of foods associated with a prudent dietary pattern is more important than totally excluding processed food , fast food , junk food , and snacks Prenatal multiple micronutrient ( MM ) supplementation improves birth weight through increased fetal growth and gestational age , but whether maternal or fetal growth factors are involved is unclear . Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh . In a double-blind , cluster-r and omized , controlled trial of MM vs. iron and folic acid ( IFA ) supplementation , we measured placental growth hormone ( PGH ) at 10 weeks and PGH and human placental lactogen ( hPL ) at 32 weeks gestation in maternal plasma ( n = 396 ) and insulin , insulin-like growth factor-1 ( IGF-1 ) , and IGF binding protein-1 ( IGFBP-1 ) in cord plasma ( n = 325 ) . Birth size and gestational age were also assessed . Early pregnancy mean ( SD ) BMI was 19.5 ( 2.4 ) kg/m2 and birth weight was 2.68 ( 0.41 ) kg . There was no effect of MM  on concentrations of maternal hPL or PGH , or cord insulin , IGF-1 , or IGFBP-1 . However , among pregnancies of female offspring , hPL concentration was higher by 1.1 mg/L in the third trimester ( 95 % CI : 0.2 , 2.0 mg/L ; p = 0.09 for interaction ) ; and among women with height < 145 cm , insulin was higher by 59 % ( 95 % CI : 3 , 115 % ; p = 0.05 for interaction ) in the MM vs. IFA group . Maternal hPL and cord blood insulin and IGF-1 were positively , and IGFBP-1 was negatively , associated with birth weight z score and other measures of birth size ( all p<0.05 ) . IGF-1 was inversely associated with gestational age ( p<0.05 ) , but other growth factors were not associated with gestational age or preterm birth .  Prenatal MM supplementation had no overall impact on intrauterine growth factors . MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring , but this should be examined in other studies . Trial Registration Clinical Trials.gov Background : Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction . Objective : We tested the hypothesis that periconceptional multiple-micronutrient supplementation ( MMS ) affects placental function . Design : We conducted a double-blind , r and omized , placebo-controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo . Eligible subjects were pre – r and omly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation ( UNIMMAP ) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive . Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ ratio of plasminogen-activator inhibitor ( PAI ) 1 to PAI-2 and mean uterine-artery resistance index ( UtARI ) ] and placental active transport capacity at delivery [ fetal to maternal measles antibody ( MMA ) ratio ] . Results : We recruited 1156 women who yielded 415 pregnancies , of which 376 met all of the inclusion criteria . With adjustment for gestational age at sampling , there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms , but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation ( 95 % CI : −0.03 , −0.00 ; P = 0.040 ) in women taking UNIMMAP . Conclusions : Placental vascular function was modifiable by periconceptional micronutrient supplementation . However , the effect was small and supplementation did not further affect other variables of placental function . This trial was registered at www.controlled-trials.com as IS RCT N 13687662 Maternal obesity has a major impact on pregnancy outcomes . There is growing evidence that maternal obesity has a negative influence on placental development and function , thereby adversely influencing offspring programming and health outcomes . However , the molecular mechanisms underlying these processes are poorly understood . We analysed ten term placenta ’s whole transcriptomes in obese ( n = 5 ) and normal weight women ( n = 5 ) , using the Affymetrix microarray platform .  Analyses of expression data were carried out using non-parametric methods . Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women . We identified 72 differentially regulated genes , with most being down-regulated in obesity ( n = 61 ) . Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women , including inflammation and immune responses , lipid metabolism , cancer pathways , and angiogenesis . In addition , we detected new molecular aspects of obesity-derived effects on the placenta , involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2 , FSTL3 , IGFBP1 , MMP12 , PRG2 , PRL , QSOX1 , SERPINE2 and TAC3 . Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome Developmental adaptations due to early nutritional exposures may have permanent health consequences . Studies of diet and fetal size have mainly focused on individual nutrients despite evidence that the pattern of food consumption may be of significance . Hence , we evaluated the associations of dietary habits in early pregnancy ( gestational age < 18 weeks ) with fetal size , uteroplacental vascular resistance , placental weight and birth weight in a prospect i ve observational study of 3207 Caucasian pregnant mothers in Rotterdam , the Netherl and s. Participants completed a semiquantitative FFQ during early pregnancy . Logistic regression  analysis was used to predict the occurrence of intra-uterine growth retardation at birth as a function of food intake . The derived solution was considered as the dietary pattern . As it was characterised by higher intakes of fruit , vegetables , vegetable oil , fish , pasta and rice , and lower intakes of meat , potatoes and fatty sauces , it was labelled the ' Mediterranean ' diet . The degree of adherence to the diet was positively associated with plasma folate and serum vitamin B12 concentrations and showed an inverse relationship with homocysteine and high-sensitivity C-reactive protein plasma concentrations ( P < 0·05 ) . Important fetal size and placental parameters were associated with the degree of adherence to the diet , revealing a 72 g lower birth weight ( 95 % CI -110·8 , -33·3 ) and a 15 g lower placental weight ( 95 % CI -29·8 , -0·2 ) for women with low adherence to the diet . To conclude , low adherence to a Mediterranean diet in early pregnancy seems associated with decreased intra-uterine size with a lower placental and a lower birth weight Background Deleterious effects of prenatal tobacco smoking on fetal growth and newborn weight are well-established . One of the proposed mechanisms underlying this relationship is alterations in epigenetic programming . We selected 506 newborns from a population -based prospect i ve birth cohort in the Netherl and s. Prenatal parental tobacco smoking was assessed using self-reporting question naires . Information on birth outcomes was obtained from medical records . The deoxyribonucleic acid ( DNA ) methylation of the growth genes IGF2DMR and H19 was measured in newborn umbilical cord white blood cells . Associations were assessed between parental tobacco smoking and DNA methylation using linear mixed models and adjusted for potential confounders . Results The DNA methylation levels of IGF2DMR and H19 in the non-smoking group were median ( 90 % range ) , 54.0 % ( 44.6–62.0 ) , and 30.0 % ( 25.5–34.0 ) , in the first trimester only smoking group 52.2 % ( 44.5–61.1 ) and 30.8 % ( 27.1–34.1 ) , and in the continued smoking group 51.6 % ( 43.9–61.3 ) and 30.2 % ( 23.7–34.8 ) , respectively . Continued prenatal maternal smoking was inversely associated with IGF2DMR methylation ( β = −1.03 , 95 % CI −1.76 ; −0.30 ) in a dose-dependent manner ( P-trend = 0.030 ) . This association seemed to be slightly more profound among newborn girls ( β = −1.38 , 95 % CI −2.63 ; −0.14 ) than boys ( β = −0.72 , 95 % CI −1.68 ; 0.24 ) . H19 methylation was also inversely associated continued smoking < 5 cigarettes/day ( β = −0.96 , 95 % CI −1.78 ; −0.14 ) . Moreover , the association between maternal smoking and newborns small for gestational age seems to be partially explained by IGF2DMR methylation ( β = −0.095 , 95 % CI −0.249 ; −0.018 ) . Among non-smoking mothers , paternal tobacco smoking was not associated with IGF2DMR or H19 methylation . Conclusions Maternal smoking is inversely associated with IGF2DMR methylation in newborns , which can be one of the underlying mechanisms through which smoking affects fetal growth OBJECTIVES To study the effect of maternal smoking on  2D ultrasound measurements and maternal serum ( MS ) levels of endocrinologic markers of placentation . STUDY DESIGN Prospect i ve population -based cohort study of 32 smokers and 96 non-smoking controls with a normal pregnancy outcome . MAIN OUTCOME MEASURES Placental thickness and 2D-volume and MS levels of pregnancy-associated plasma protein A ( PAPP-A ) and free-beta human chorionic gonadotrophin ( fβhCG ) at 11 - 13(+6)weeks of gestation and mid-trimester MS α-fetoprotein ( AFP ) , unconjugated estriol ( uE3 ) and inhibin A levels . RESULTS The MS levels of fβhCG and PAPP-A were significantly ( P < 0.01 and P < 0.001 , respectively ) lower in the serum and the level of inhibin A significantly ( P < 0.001 ) higher in the smokers than in controls . There was no significant difference for the MSAFP , MSuE3 placental thickness , basal plate surface and volume between the groups . CONCLUSION The placental morphological alterations secondary to maternal smoking are mainly at the level of the villous trophoblast and are not associated with changes in the placental size or utero-placental interface during the first trimester of pregnancy The aim of this study was to determine the effects of tobacco use and consumption of caffeine in pregnancy on the fetus and placenta by measuring the body weights , head circumferences , and lengths of newborns , and also weights and diameters of placentas . In this prospect i ve study , two main groups were chosen for the study : Group I : A total of 63 pregnant non-smokers ; were separated into two subgroups according to their daily caffeine intake ; less than 300 mg ( Ia ) ( n = 44 ) , and more than 300 mg ( Ib ) ( n = 19 ) . Group II : 60 pregnant smokers were also separated into two subgroups ; daily caffeine intake less than 300 mg ( IIa ) ( n = 43 ) , and more than 300 mg ( IIb ) ( n = 17 ) . The newborns and placentas of both groups were examined . The body weights , lengths , and head circumferences of newborns and also weights and diameters of placentas were measured . The pregnant non-smokers consuming caffeine more than 300 mg/day had statistically significant lower weights of newborns and placentas ( p < 0.05 ) . However , there was no significant difference between groups according to the lengths , head circumferences of newborns and diameters of placentas . There were significantly lower body weights of newborns and placentas in pregnant smokers ( p < 0.05 ) . There was no difference according to the diameters of placentas , and lengths and head circumferences of newborns in either group . In conclusion , it is suggested that smoking in pregnancy should be prevented both for the health of newborns and mothers , and also caffeine including beverages like tea and coffee should be limited in pregnancy OBJECTIVE We sought to study midpregnancy placental volume in rural Indian women , its maternal determinants , and its relationship to neonatal size . STUDY DESIGN We performed a prospect i ve community-based study of  maternal nutrition and fetal growth in 6 villages near the city of Pune . Measurements included midpregnancy placental volume determined by means of ultrasonography at 15 to 18 weeks ' gestation , maternal anthropometric measurements before and during pregnancy , and maternal blood pressure and biochemical parameters during pregnancy . Neonatal size and placental weight were measured at birth . RESULTS The mothers were short and underweight ( mean height , 1.52 m ; weight , 42 kg ; body mass index , 18 kg/m(2 ) ) and produced small babies ( mean birth weight , 2648 g ) . Midpregnancy placental volume ( median , 144 mL ) was related to the mother 's prepregnancy weight ( r = 0.15 ; P < .001 ) but not to weight gain during pregnancy , blood pressure , or circulating hemoglobin , ferritin , red blood cell folate , or glucose concentrations . Midpregnancy placental volume was related to placental weight at birth ( r = 0.29 ; P < .001 ) and birth weight ( r = 0.25 ; P < .001 ) independent of maternal size . CONCLUSION In Indian mothers midpregnancy placental volume is significantly associated with prepregnant maternal weight and is an independent predictor of birth weight . Our findings may provide clues to the high prevalence of low-birth-weight infants in India Background Unhealthy nutrition and lifestyle contribute to the worldwide rising prevalence of non-communicable diseases . This also accounts for the reproductive population , in which unhealthy behavior affects fertility and pregnancy outcome . Maternal smoking , alcohol consumption and inadequate folic acid supplement use are strongly associated with fetal complications as small for gestational age , premature birth and congenital malformations . In the Netherl and s 83 % of the perinatal mortality rate is due to these complications and is relatively high compared to other European countries . In order to reduce this prevalence rate , preconception care should be focused on the promotion of health of prospect i ve parents by identification and intervention on modifiable nutrition and lifestyle risk factors . We developed the personal mHealth program ‘ Smarter Pregnancy ’ ( Dutch version available on : https://www.slimmerzwanger.nl ) to provide individual coaching and information to improve nutrition and lifestyle during the preconception period in order to improve health of the reproductive population and subsequent generations . Methods Women between 18 and 45 years of age , and trying to conceive are eligible for inclusion in a r and omized controlled trial . Participants are allocated either to a general population cohort or a subfertile ( IVF/ICSI ) population cohort . The intervention group receives personal online coaching based on the identified nutrition and lifestyle risk factors at baseline . Coaching comprises recipes , incentives , additional questions including feedback and text and e-mail messages , with a maximum of three per week . The control group only receives one recipe per week to maintain adherence to the program and prevent drop out . Screening question naires are send in both groups at 6 , 12 , 18 , and 24 weeks of the program to monitor the change in the identified risk factors . Discussion We expect to demonstrate that the mHealth program ‘ Smarter Pregnancy ’ can effectively improve nutrition and lifestyle in couples contemplating pregnancy . By the identification and improvement of modifiable nutrition and lifestyle risk factors on a large scale , both reproductive and pregnancy outcomes can be improved and subsequent perinatal morbidity and mortality rates are expected to be reduced . The current use and rapid development of mHealth applications offers new opportunities to reach and educate large population s , which can facilitate the implementation of preconception care . Trial registration Dutch trial register : NTR4150 . ( Registered 19th August 2013 Background Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth . We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth : placental thickness and chorionic plate area . Methods We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project , a prospect i ve cohort study of pregnancy and child health . We defined growth restriction as < 10th percentile and hypertrophy as > 90th percentile for three placental growth dimensions : placental weight , placental thickness and chorionic plate area . We constructed parallel multinomial logistic regression analyses to identify ( a ) predictors of restricted growth ( vs. normal ) and ( b ) predictors of hypertrophic growth ( vs. normal ) . Results Black race was associated with an increased likelihood of growth restriction for placental weight , thickness and chorionic plate area , but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions . We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond .  Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area . Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth . Conclusion Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both . Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms Background Despite the existence of various published studies regarding the effects of tobacco smoking on pregnancy , and especially in regards to placental blood flow and vascular resistance , some points still require clarification . In addition , the amount of damage due to tobacco smoking exposure that occurs has not been quantified by objective means . In this study , we looked for a possible association between flow resistance indices of several arteries and the levels of urinary cotinine and the concentration of carbon monoxide in the exhaled air ( COex ) of both smoking and non-smoking pregnant women . We also looked for a relationship between those findings and fetal growth and birth weight . Methods In a prospect i ve design , thirty pregnant smokers and thirty-four pregnant non-smokers were studied . The volunteers signed consent forms , completed a self-applied question naire and were subjected to Doppler velocimetry . Tobacco smoking exposure was quantified by subject provided information and confirmed by the measurement of urinary cotinine levels and by the concentration of carbon monoxide in the exhaled air ( COex ) . The weight of newborns was evaluated immediately after birth . Results Comparing smoking to non-smoking pregnant women , a significant increase in the resistance index was observed in the uterine arteries ( P = 0.001 ) and umbilical artery ( P = 0.001 ) , and a decrease in the middle cerebral artery ( P = 0.450 ) . These findings were associated with progressively higher concentrations of COex and urinary cotinine . A decrease in the birth weight was also detected ( P < 0.001 ) in association with a progressive increase in the tobacco exposure of the pregnant woman . Conclusions In pregnant women who smoke , higher arterial resistance indices and lower birth weights were observed , and these findings were associated with increasing levels of tobacco smoking exposure . The values were significantly different when compared to those found in non-smoking pregnant women . This study contributes to the findings that smoking damage during pregnancy is dose-dependent , as demonstrated by the objective methods for measuring tobacco smoking exposure INTRODUCTION Angiogenic factors , such as placental growth factor ( PlGF ) and soluble Flt-1 ( sFlt-1 ) , are key regulators of placental vascular development . Evidence from in vitro studies indicates that fatty acids can affect angiogenesis . We investigated the associations of maternal fish consumption  and fatty acids levels with angiogenic factors during pregnancy , and in cord blood in a large population -based prospect i ve cohort . METHODS  First trimester fish consumption was assessed among 3134 pregnant women using a food-frequency question naire . Plasma fatty acid levels were measured in second trimester . Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood . Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses . RESULTS There were no consistent associations of total fish or lean fish consumption with levels of PlGF , sFlt-1 , or sFlt-1/PlGF ratio . Neither fatty fish nor shellfish were associated with angiogenic factors . Plasma omega-3 polyunsaturated fatty acids , which are the main type of fatty acids in fish , were inconsistently associated with angiogenic factors in second trimester and cord blood . Yet , higher levels of arachidonic acid , an omega-6 polyunsaturated fatty acid , were associated with lower levels of PlGF and sFlt-1 . DISCUSSION We found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption . Studies including population s with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis OBJECTIVE The study aims to evaluate first-trimester vascularization of the placenta and subplacental myometrium in women who subsequently develop preeclampsia . STUDY DESIGN A case-control study nested in a prospect i ve cohort was conducted in women with singleton pregnancy between 11 and 14 weeks ' gestation .  Three-dimensional st and ardized acquisition of the placenta and subplacental myometrium volumes with and without power Doppler was undertaken , and all participants were followed up until delivery . Each woman diagnosed with preeclampsia was matched with three controls who delivered at term without pregnancy complications . First-trimester volume , vascularization index ( VI ) , flow index ( FI ) , and vascular flow index ( VFI ) of the entire placenta and subplacental myometrium were measured separately . The results were stratified for preterm and term preeclampsia , respectively . RESULTS A total of 1,034 women were recruited , including 16 ( 1.5 % ) who developed term preeclampsia and 4 ( 0.4 % ) who developed preterm preeclampsia .  Preeclampsia was associated with a significantly lower placental VI , placental VFI , subplacental VI , and subplacental VFI in the first trimester than with the controls ( all p < 0.05 ) . All cases ( 4/4 ) of preterm preeclampsia , 56 % ( 9/16 ) of term preeclampsia , and 28 % ( 17/60 ) of the controls had a subplacental VI below 18 % ( p < 0.01 ) . CONCLUSION First-trimester placental and subplacental myometrium vascularizations are significantly reduced in women who subsequently develop preeclampsia INTRODUCTION Placental biometry at birth has been shown to predict chronic disease in later life . We hypothesized that maternal overweight/obesity , a state of low- grade inflammation and risk factor for adverse pregnancy outcome , could negatively influence placental development and that differences would be sex-specific . METHODS 696 women ( 537 normal-weight , NW ; 112 overweight , OW ; 47 obese , OB ) with singleton uncomplicated pregnancies were prospect ively enrolled at term delivery .  Gestational age , maternal ( age , height , pre-pregnancy BMI , gestational weight gain -GWG , hemoglobin , hematocrit and glycemia ) , fetal ( weight , length , ponderal index , cranial circumference ) and placental ( weight , diameters ) data  were collected . Placental area , thickness and efficiency ( fetal/placental weight ratio , F/P ) were calculated . RESULTS GWG was within st and ard recommendations in OB , while OW exceeded it . Placental weight was significantly higher in OW versus NW , but not in OB , leading to significantly higher placental thickness and lower F/P in this group . In the total population , a significant interaction effect between maternal BMI and fetal sex on placental weight and efficiency was found . Indeed , differences in placental parameters were present only in female offspring . DISCUSSION In our population of OW and OB uncomplicated pregnancies only OW women , presenting GWG over st and ard recommendations , had thicker and less efficient placentas . We also reported different placental adaptation depending on fetal sex , with significant changes only in female fetuses . This may be part of a female-specific strategy aim ing to ensure survival if another adverse event occurs . Customized counseling according to maternal BMI and fetal sex should be evaluated in clinical care Experimental studies indicate that fetal undernutrition programmes life-long physiology and disease risk . The objective of this study was to investigate relationships between maternal nutrient intakes in early and late pregnancy with birth weights , placental weights , and infant proportions at birth . A prospect i ve cohort study set in a district general hospital in the east midl and s of Engl and considered the  diets of 300 pregnant women recruited from an antenatal ultrasound dating scan clinic . Estimation of nutrient intakes utilised five-day food diaries in the first and third trimesters of pregnancy . Two hundred and four diaries were returned and analysed for trimester one and 176 for trimester three . Birth weight and infant head circumference at birth were unrelated to nutrient intakes in the first or third trimester of pregnancy . Placental weight was not related to any maternal nutrient intakes . Thinness at birth was associated with low contributions of carbohydrate to dietary energy ( p=0.036 ) . The present study shows that maternal nutrition in well-nourished population s does not exert a strong influence upon fetal growth . These data suggest that reported associations between low weight , thinness or greater head circumference at birth and disease in later life are not attributable to the effects of maternal undernutrition OBJECTIVE In this study , we aim ed to investigate relationships between maternal prepregnancy obesity and gestational diabetes mellitus and placental leptin DNA methylation . STUDY DESIGN This study comprises data on 535 mother-infant dyads enrolled in the Rhode Isl and Child Health Study , a prospect i ve cohort study of healthy term pregnancies . Prepregnancy body mass index was calculated from self-reported anthropometric measures and gestational diabetes mellitus diagnoses gathered from inpatient medical records . DNA methylation of the leptin promoter region was assessed in placental tissue collected at birth using quantitative bisulfite pyrosequencing . RESULTS In a multivariable regression analysis adjusted for confounders , infants exposed to gestational diabetes mellitus had higher placental leptin methylation ( β = 1.89 , P = .04 ) , as did those demonstrating prepregnancy obesity ( β = 1.17 , P = .06 ) . Using a structural equations model , we observed that gestational diabetes mellitus is a mediator of the effects of prepregnancy obesity on placental leptin DNA methylation ( β = 0.81 , 95 % confidence interval , 0.27 - 2.71 ) . CONCLUSION Our results suggest that the maternal metabolic status before and during pregnancy can alter placental DNA methylation profile at birth and potentially contribute to metabolic programming of obesity and related conditions Placental growth is a strong predictor of fetal growth , but little is known about maternal predictors of placental growth in malnourished population s. Our objective was to investigate in a prospect i ve study the associations of maternal weight and body composition [ total body water ( TBW ) estimated by bioelectrical impedance and fat and fat-free mass derived from upper arm fat and muscle areas ( UAFA , UAMA ) ] and changes in these with placental and birth weights . Within a cluster-r and omized trial of maternal micronutrient supplementation  , a sub sample of 350 women was measured 3 times across gestation . Longitudinal analysis was used to examine independent associations of ∼10-wk measurements and ∼10 - 20 wk and ∼20 - 32 wk changes with birth outcomes . Weight , TBW , and UAMA , but not UAFA , at ∼10 wk were each positively and independently associated with placental weight and birth weight ( P < 0.05 ) . Of the maternal ∼10 - 20 wk changes in measurements , only TBW change and placental weight , and maternal weight and birth weight were positively associated ( P < 0.05 ) . Gains in weight , TBW , and UAMA from 20 to 32 wk were positively and UAFA gain was negatively associated with placental weight ( P ≤ 0.01 ) . Gains in weight and UAMA from 20 to 32 wk were positively associated with birth weight ( P ≤ 0.01 ) . Overall , higher maternal weight and measures of fat-free mass at ∼10 wk gestation and gains from 20 to 32 wk are independently associated with higher placental and birth weight Objective : To examine the maternal and neonatal factors associated with offspring adiposity and the role of birth and placental weight as potential mediators in such associations . Design : The  Tasmanian Infant Health Survey  was a prospect i ve cohort study conducted between 1988 and 1995 in Australia to investigate the cause of Sudden Infant Death Syndrome . This large infant cohort provides measurement of skinfolds on 7945 mothers and their offspring . Subjects : Participants included singletons born ⩾37 weeks gestation who were at high risk of sudden infant death syndrome identified through a composite score that included birth weight , maternal age , neonatal gender , season of birth , duration of second-stage labor and intention to breastfeed . Measurements : Neonatal adiposity was assessed from skinfold measurements of the subscapular ( SSF ) and triceps folds ( TSF ) taken at birth . Maternal early-pregnancy body mass index ( BMI ) was calculated from self-reported height and weight . Neonatal data were extracted from birth records . Data relating to other environmental exposures were obtained from question naires administered when neonates were ∼4-days old . Results : In multivariable models , higher maternal adiposity , increasing maternal age , gestation age , delivery by Caesarian section and female gender were associated with larger SSF independent of placental and birth weight ( P<0.001 ) . Maternal age and delivery by Caesarian section were significantly associated with larger TSF , whereas gestational age and male gender were associated with thinner TSF independent of placental and birth weight . Higher early-pregnancy BMI , maternal weight gain , maternal age , parity and gestational age were significantly associated with larger placental and birth weight . Smoking during pregnancy was associated with smaller birth weight but not with placental weight . Conclusion : In addition to birth weight , maternal adiposity and placental weight were important additional factors associated with neonatal adiposity Abstract Background : Maternal obesity is a frequent obstetric risk factor , linked with short- and long-term consequences for mother and child , including foetal overgrowth , growth restriction and stillbirth . The mechanisms underlying these pathologies remain unknown but likely involve the placenta . Aims : To study placental cell turnover in relation to maternal body mass index ( BMI ) . Methods : Term placental villous tissue was r and omly sample d from 24 pregnancies , with a range of maternal BMI of 19.5–49.6 .  Immunohistochemistry was performed for human chorionic gonadotropin , Ki67 and M30 and image analysis used to calculate syncytiotrophoblast area and proliferative and apoptotic indices . Results were compared categorically between women of BMI 18.5–24.9 ( normal ) , BMI 30.0–39.9 ( obese classes 1 and 2 ) and BMI 40 + ( obese class 3 ) and continuously against BMI ; p < 0.05 by the Kruskal – Wallis test or linear regression was considered statistically significant . Results : Increased maternal BMI was associated with categorical ( normal versus obese class 3 and obese classes 1 and 2 versus obese class 3 , both p < 0.05 ) and continuous ( r2 = 0.24 , p = 0.016 ) reductions in the proliferative index and a continuous reduction ( r2 = 0.17 , p = 0.047 ) in the apoptotic index . Discussion : Maternal obesity is associated with a dose-dependent reduction in placental villous proliferation and apoptosis which may increase susceptibility to adverse pregnancy outcomes INTRODUCTION Obesity during pregnancy is associated with a wide spectrum of maternal , fetal and neonatal complications . This study compared placental pathology in women with obesity and normal weight gravidas . MATERIAL S AND METHODS This is a retrospective case-control study . The sample was r and omly selected from a total of 1000 deliveries of largely Caucasian population in a single institution , recruited for the study of sleep disordered breathing , where the placenta is su bmi tted for pathological examination for clinical indications based on national guidelines . Cases ( Body mass index - BMI ≥ 30 kg/m(2 ) ; n = 47 ) and controls ( BMI < 25 kg/m(2 ) , n = 45 ) were selected based on BMI obtained from the first prenatal visit . Placental pathology , clinical parameters and limited outcomes were extracted from medical records . Placental weight range was defined as small for gestational age ( SGA ) if < 10th percentile , large for gestational age ( LGA ) if > 90th percentile . RESULTS Mean BMI was 36.2 ± 5.5 in the group with obesity and 21.7 ± 1.9 in the control group ( p < 0.01 ) . There was a significantly higher prevalence of diabetes in cases compared to controls ( 14/47 vs. 3/45 , p = 0.006 ) while preterm birth was significantly higher in the control group ( 9/47 vs. 19/46 , p = 0.02 ) . There were more LGA placentas in cases versus controls ( 12/47 vs. 2/46 , p = 0.007 ; even after adjusting for diabetes ) . More histological features of inflammation , marginal insertion of the umbilical cord and intervillous thrombi in the parenchyma were also noted in the case group . CONCLUSIONS Results from the current study suggest that maternal obesity measured at early pregnancy may have effects on both placental implantation and growth , and further exacerbate the hypercoagulable state in placenta BACKGROUND Alterations in circulating soluble fms-like tyrosine kinase 1 ( sFlt1 ) , an antiangiogenic protein , and placental growth factor ( PlGF ) , a proangiogenic protein , appear to be involved in the pathogenesis of preeclampsia . Since soluble endoglin , another antiangiogenic protein , acts together with sFlt1 to induce a severe preeclampsia-like syndrome in pregnant rats , we examined whether it is associated with preeclampsia in women . METHODS We performed a nested case-control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention trial . The study included all 72 women who had preterm preeclampsia ( < 37 weeks ) , as well as 480 r and omly selected women--120 women with preeclampsia at term ( at > or = 37 weeks ) , 120 women with gestational hypertension , 120 normotensive women who delivered infants who were small for gestational age , and 120 normotensive controls who delivered infants who were not small for gestational age . RESULTS Circulating soluble endoglin levels increased markedly beginning 2 to 3 months before the onset of preeclampsia . After the onset of clinical disease , the mean serum level in women with preterm preeclampsia was 46.4 ng per milliliter , as compared with 9.8 ng per milliliter in controls ( P<0.001 ) . The mean serum level in women with preeclampsia at term was 31.0 ng per milliliter , as compared with 13.3 ng per milliliter in controls ( P<0.001 ) . Beginning at 17 weeks through 20 weeks of gestation , soluble endoglin levels were significantly higher in women in whom preterm preeclampsia later developed than in controls ( 10.2 ng per milliliter vs. 5.8 ng per milliliter , P<0.001 ) , and at 25 through 28 weeks of gestation , the levels were significantly higher in women in whom term preeclampsia developed than in controls ( 8.5 ng per milliliter vs. 5.9 ng per milliliter , P<0.001 ) . An increased level of soluble endoglin was usually accompanied by an increased ratio of sFlt1:PlGF . The risk of preeclampsia was greatest among women in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone . CONCLUSIONS Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia STUDY QUESTION Are maternal characteristics and lifestyle factors associated with  human embryonic growth trajectories ? SUMMARY ANSWER Periconception maternal age is associated with increased , and smoking and alcohol use with decreased embryonic growth trajectories , estimated with crown-rump length ( CRL ) measurements . WHAT IS KNOWN ALREADY Fetal weight is associated with health and disease in later life . Maternal characteristics and lifestyle factors affect fetal growth in the second and third trimesters of pregnancy and at birth ; however , little is known about the association of these characteristics with first trimester embryonic growth . STUDY DESIGN , SIZE , DURATION In a tertiary centre , pregnant women were recruited and enrolled in a prospect i ve periconception cohort study before 8 weeks of gestation . We selected 87 spontaneously conceived singleton pregnancies of women recruited in 2009 and 2010 that ended in non-malformed live births . PARTICIPANTS / MATERIAL S , SETTING , METHODS We performed weekly three-dimensional ultrasound scans from enrolment up to 13 weeks of gestation . At enrolment , a question naire was completed . Embryonic CRL measurements were performed using the V-Scope software in the BARCO I-Space . Associations between maternal characteristics and embryonic growth were assessed using square root transformed CRL as response in linear mixed model analyses , adjusted for potential confounders . MAIN RESULTS AND THE ROLE OF CHANCE Four hundred and ninety-six scans from 87 pregnancies were included . In the multivariable analysis , maternal age was positively associated with first trimester CRL ( difference per maternal year of age 0.024√mm ( 95 % confidence interval ( CI ) 0.009 , 0.040 ) , P = 0.001 ) . At 6 and 12 weeks of gestation , the CRL of an embryo from a 40-year-old mother was estimated 2.0 mm ( 61 % ) and 7.2 mm ( 14 % ) larger , respectively , compared with an embryo from a 20-year-old mother . Smoking of 10 or more cigarettes per day was negatively associated with CRL ( difference -0.211√mm ( 95 % CI -0.416 , -0.006 ) , P = 0.04 ) , with embryos that were 0.9 mm ( 18.7 % ) and 3.1 mm ( 5.5 % ) smaller at 6 and 12 weeks , respectively , compared with non-smokers . Periconception alcohol use was negatively associated with CRL growth rate ( difference -0.0025√mm ( 95 % CI -0.0047 , -0.0003)/day gestational age , P = 0.022 ) , with embryos that were 0.2 mm ( 3 % ) and 1.1 mm ( 2 % ) smaller at 6 and 12 weeks , respectively , compared with non-alcohol users . Parity , BMI and moment of initiation of folic acid use were not significantly associated with embryonic CRL . LIMITATIONS , REASONS FOR CAUTION Due to the selection of pregnancies in a tertiary centre and the small number of pregnancies , the external validity of the results has to be confirmed using larger sample sizes and other population -based periconception cohort studies . WIDER IMPLICATION S OF THE FINDINGS The association of maternal age and smoking with embryonic growth is in line with previous literature , whereas the association between embryonic growth and alcohol use is a new finding . However , concerning exposure to alcohol , the effect estimate was small and it is question able whether this is of clinical value . More research is warranted to unravel underlying mechanisms and to assess the implication s for preconception and early pregnancy care , such as the development and implementation of effective lifestyle interventions . STUDY FUNDING /COMPETING INTEREST(S ) The work was funded by the Department of Obstetrics and Gynaecology , Erasmus MC , University Medical Centre , Rotterdam , The Netherl and s. The authors declare no conflicts of interest BACKGROUND Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia . In the nonpregnant , obesity is associated with dyslipidemia , vascular dysfunction , and low- grade chronic inflammation . AIM Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery . Plasma markers of endothelial function , inflammation , and placental function and their association with microvascular function were also assessed . METHODS Women in the 1st trimester of pregnancy were recruited , 30 with a body mass index ( BMI ) less than 30 kg/m(2 ) and 30 with a BMI more than or equal to 30 kg/m(2 ) matched for age , parity , and smoking status .  In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st , 2nd , and 3rd trimesters of pregnancy and at 4 months postnatal . Plasma markers of endothelial activation [ soluble intercellular cell adhesion molecule-1 ( sVCAM-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , von Willebr and factor ( vWF ) , and plasminogen activator inhibitor (PAI)-1 ] , inflammation ( IL-6 , TNFalpha , C-reactive protein , and IL-10 ) , and placental function ( PAI-1/PAI-2 ratio ) were also assessed at each time point . RESULTS The pattern of improving endothelial function during pregnancy was the same for lean and obese , but endothelial-dependent vasodilation was significantly lower ( P < 0.05 ) in the obese women at each trimester ( 51 , 41 , and 39 % , respectively ) . In the postpartum period , the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese ( lean/obese difference , 115 % ; P < 0.01 ) . There was a small but significant difference in endothelial-independent vasodilation between the two groups , lean response being greater than obese ( P = 0.021 ) , and response declined in both groups in the postpartum period . In multivariate analysis , time of sampling had the most impact on endothelial-independent function [ 18.5 % ( adjusted sum of squares expressed as a percentage of total means squared ) , P < 0.001 for sodium nitroprusside response ; 9.8 % , P < 0.001 for acetylcholine response ] , and obesity had the most impact on endothelial-dependent microvascular function ( 1.7 % , P = 0.046 for sodium nitroprusside response ; 19.3 % , P < 0.001 for acetylcholine response ) . Time of sampling ( 11.2 % , P < 0.001 ) , IL-6 ( 4.0 % , P = 0.002 ) , and IL-10 ( 2.4 % , P = 0.018 ) were significant independent contributors to variation in endothelial-dependent microvascular function . When obesity was entered into the model , the association with IL-6 and IL-10 was no longer significant , and obesity explained 6.8 % ( P < 0.001 ) of the variability in endothelial-dependent microvascular function . In the 1st trimester , obese women had a significantly higher PAI-1/PAI-2 ratio [ obese median ( interquartile range ) , 0.87 ( 0.54 - 1.21 ) vs. lean 0.30 ( 0.21 - 0.47 ) , P < 0.001 ) , reflecting the lower PAI-2 levels in obese pregnant women . In a multivariate analysis , 1st trimester BMI ( 7.6 % , P = 0.012 ) , IL-10 ( 8.2 % , P < 0.001 ) , and sVCAM-1 ( 0.73 % , P = 0.007 ) contributed to the 1st trimester PAI-1/PAI-2 ratio . CONCLUSION Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts . There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women , which improved later in pregnancy . Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines Placental GH is thought to be responsible for the rise in maternal IGF-I during pregnancy and is considered to be important for fetal growth . In this prospect i ve longitudinal study of healthy pregnant women , we investigated determinants of placental GH in maternal serum . Serum was obtained from 455 women with normal singleton pregnancies at approximately 19 and 28 wk gestation .  Serum placental GH concentrations were measured by a highly specific immunoradiometric assay , and fetal size was measured by ultrasound . Data on birth weight , gender , prepregnancy body mass index ( BMI ) , parity , and smoking habits were obtained from medical records . Serum placental GH concentrations were detectable in serum from all women as early as 14 wk gestation and increased during pregnancy in all individuals ( P < 0.001 ) . Placental GH levels at second examination were found to be higher in women carrying female fetuses [ median , 9.0 ng/ml ; 95 % confidence interval ( CI ) , 4.7 - 23.0 ] compared with women carrying male fetuses ( median , 8.2 ng/ml ; 95 % CI , 3.96 - 19.4 ; P = 0.004 ) . Similarly , the increase in placental GH between 19 and 28 wk gestation was significantly larger in female fetus bearers than in male fetus bearers ( P = 0.002 ) . Placental GH at second examination was positively correlated with gestational age ( P = 0.002 ) and negatively correlated with prepregnancy BMI ( P = 0.039 ) . Placental GH correlated with fetal weight at approximately 28 wk gestation ( P = 0.002 ) but did not predict birth weight at term . Our study supports the role of maternal placental GH in the regulation of fetal growth . In conclusion , we found that 1 ) placental GH levels correlated significantly with fetal size at 28 wk gestation ; 2 ) GH levels were measurable in serum from all women as early as 14 wk gestation ; 3 ) maternal prepregnancy BMI and smoking were determinants of placental GH levels , although their specific effects on the serum maternal levels of placental GH remain to be seen ; and 4 ) women carrying female fetuses have significantly higher placental GH levels compared with women carrying male fetuses at 28 wk gestation OBJECTIVE Recommendations on folic acid use to prevent neural tube defects have been launched in several countries . Adequate folic acid use seems to be low . This study assesses the prevalence of folic acid use and identifies its determinants . METHODS The study was embedded in the Generation R Study Rotterdam , the Netherl and s , a population -based prospect i ve cohort study between 2002 and 2006 . Complete information of 6940 women was available . Information on folic acid use and potential determinants was obtained by question naires and physical examination . RESULTS Of all women 37 % adequately used folic acid during the preconception period . Most important risk factors for inadequate use were unplanned pregnancy ( OR 9.5 , CI 7.2 - 12.4 , p<0.001 ) , low educational level ( OR 2.5 , CI 1.8 - 3.6 , p<0.001 ) and non-western ethnicity , ( OR 3.5 , CI 2.9 - 4.3 , p<0.001 ) . After stratification for ethnicity , unplanned pregnancy remained the most important risk factor for inadequate use . Other risk factors for inadequate use were younger age , single marital status , smoking , multiparity ( all p<0.001 ) and alcohol use ( p<0.05 ) . In contrast , previous spontaneous abortion decreased the risk of inadequate folic acid use ( p<0.001 ) . CONCLUSION Adequate preconception folic acid supplementation is still too low . Implementation of preconception programs and other public health strategies are strongly needed
BACKGROUND Worldwide , placenta-related complications contribute to adverse pregnancy outcomes , such as pre-eclampsia , fetal growth restriction and preterm birth , with implication s for the future health of mothers and offspring .
The placenta develops in the periconception period and forms the interface between mother and embryo/fetus .
An unhealthy periconceptional maternal lifestyle , such as smoking , alcohol and under- and over-nutrition , can detrimentally influence placental development and function .
OBJECTIVE AND RATIONALE The impact of maternal lifestyle on placental health is largely unknown .
Therefore , we aim to summarize the evidence of the impact of periconceptional maternal lifestyle on clinical features and biomarkers of placental development and function throughout pregnancy .