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Introduction: This retrospective study investigated the hypothesis that maternal hemoglobin (Hb) levels in twin pregnancy fall between the first and second trimesters and that higher falls are associated with higher gestational age at birth and higher birthweight (BW)., Material and Methods: The study population was defined as pregnant women with twin pregnancies delivering two live, phenotypically normal neonates, after 24 +0 weeks of gestation, between October 2009 and September 2021 at an inner London maternity unit. Maternal Hb and mean corpuscular volume (MCV), at ≤14 +0 weeks of gestation (Hb1) and again at 20 +0 -30 +0 weeks gestation (Hb2) were recorded from the Hospital's perinatal database. MCV was used as a possible indicator of iron deficiency anemia. The association of Hb drop, defined as [Hb1(adjusted for gestational age) - Hb2], and MCV values with gestational age at birth, BW of both twins and delivery of small for gestational age (SGA) neonates, defined as BW <10th percentile for gestation, was evaluated., Results: 923 pregnant women with twin pregnancies were included. Maternal Hb1 did not correlate with any outcomes measured. However, a lower Hb2 and a larger Hb drop was associated with a higher gestational age at birth (p < 0.001), a larger BW of twin 1 and 2 (p < 0.001 for both) and a reduction in the incidence of delivering one or two SGA neonates (p < 0.001 for both). MCV values did not correlate significantly with these outcomes., Conclusions: This study showed that in twin pregnancy, a larger maternal Hb drop from the first to the second trimester is associated with a higher gestational age at birth and a larger BW. This change may represent a larger plasma volume expansion., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

The obesity epidemic is growing and poses significant risks to pregnancy. Metabolic impairment can be associated with short- and long-term maternal and perinatal morbidity and mortality. The cardiovascular implications are known in those with metabolic disorder outside of pregnancy; however, little is known of the cardiac function in pregnancies complicated by obesity. Maternal cardiac adaptation plays a vital role in normal pregnancy and is known to be involved in the pathophysiology of adverse pregnancy outcomes. Bariatric surgery is the most successful treatment for sustainable weight loss and pre-pregnancy bariatric surgery can drastically change the maternal metabolic profile and pregnancy outcomes. In this review, we discuss the available evidence on maternal cardiac function in pregnancies affected by obesity and its associated consequences of gestational diabetes and hypertension (chronic and hypertensive disorders in pregnancy), as well as pregnancies following bariatric surgery., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

Introduction: Obesity is known to be associated with cardiovascular compromise and a major risk factor for the development of hypertensive disorders in pregnancy. However, little is known about the effect of obesity on maternal cardiac function. The aim of this study was to investigate the effect of obesity on the maternal cardiovascular system., Material and Methods: This was a prospective, observational, longitudinal study. Pregnant women with booking body mass index (BMI) ≥30 kg/m 2 were compared with pregnant women with normal booking BMI 20-24.9 kg/m 2 . Participants were seen at three time points during pregnancy; 12-14, 20-24 and 30-32 weeks. At all visits, maternal blood pressure (BP) was measured, and cardiac geometry and function were assessed using two-dimensional trans-thoracic echocardiography. Multilevel linear mixed-effects models were used for all the comparisons., Results: Fifty-nine pregnant women with obesity were compared with 14 pregnant women with normal BMI. In women with obesity, the maternal BP, heart rate and cardiac output were higher and peripheral vascular resistance was lower (p < 0.01 for all comparisons) compared with normal BMI women. Women with obesity had altered cardiac geometry with higher left ventricular end diastolic diameter, intraventricular septal thickness, posterior wall diameter, relative wall thickness and left ventricular mass (p < 0.001 for all comparisons). There was also evidence of impaired diastolic indices in the obese group with a lower E/A ratio, tissue Doppler imaging E' lateral and medial and higher left atrial volume (p < 0.01 for all comparisons). Finally, women with obesity had reduced longitudinal function, as assessed by mitral plane annular systolic excursion, between the second and third trimester of pregnancy, indicating possible early cardiac dysfunction in this group., Conclusions: Obesity is associated with maternal hyperdynamic circulation, altered cardiac geometry and suboptimal diastolic function, compared with normal BMI pregnant women, and these factors may contribute to the increased risk of complications in obese pregnant women., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Bariatric surgery is a successful treatment for sustainable weight loss and has been associated with improvement in cardiovascular function. Pregnancy after bariatric surgery is becoming increasingly common; however, little is known about the maternal cardiovascular system postsurgery. The aim of this study was to investigate maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery, compared with that in women with no history of weight-loss surgery and an early-pregnancy body mass index (BMI) similar to the presurgery BMI of the postbariatric women., Methods: This was a prospective, observational, longitudinal study conducted from April 2018 to June 2020 including 30 pregnant women who had undergone bariatric surgery and 30 who had not, matched for presurgery BMI. Participants were seen at three timepoints during pregnancy: 12-14, 20-24 and 30-32 weeks' gestation. At all visits, maternal blood pressure (BP) was measured and cardiac geometry and function were assessed using two-dimensional (2D) transthoracic echocardiography. On a subset of patients (15 in each group), 2D speckle tracking was performed to assess global longitudinal and circumferential strain. Offline analysis was performed, and multilevel linear mixed-effects models were used for all comparisons., Results: Compared with the no-surgery group, and across all trimesters, pregnant women with previous bariatric surgery had lower BP, heart rate and cardiac output and higher peripheral vascular resistance (P < 0.01 for all). Similarly, the postbariatric group demonstrated more favorable cardiac geometry and diastolic indices, including lower left ventricular mass, left atrial volume and relative wall thickness, together with higher E-wave/A-wave flow velocity across the mitral valve and higher mitral velocity (E') at the lateral and medial annulus on tissue Doppler imaging (P < 0.01 for all). There was no difference in ejection fraction, although global longitudinal strain was lower in postbariatric women (P < 0.01), indicating better systolic function., Conclusion: Our findings indicate better maternal cardiovascular adaptation in women with previous bariatric surgery compared with presurgery BMI-matched pregnant women with no history of weight-loss surgery. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Obesity in pregnancy is associated with substantial risks, notably hypertensive disorders. Bariatric surgery achieves sustained weight loss and has several cardiovascular benefits, including positive effects on blood pressure, cardiac geometry, and both systolic and diastolic function. Pregnancy following bariatric surgery is also associated with improved outcomes, including a reduced risk of hypertensive disorders. The underlying mechanisms, however, remain uncertain. Maternal cardiovascular adaptation plays a vital role in maintaining a healthy pregnancy, and maladaptation has been associated with adverse pregnancy outcomes. However, to date, the maternal cardiovascular adaptation to pregnancy after bariatric surgery has not been investigated., Objective: To investigate the maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery compared with women with a similar early-pregnancy body mass index, age, and race but no history of weight loss surgery., Study Design: This was a prospective, observational, longitudinal study including pregnant women with (n=41) and without (n=41) a history of bariatric surgery. The participants were seen at 3 time points; at 12 to 14, 20 to 24, and 30 to 32 weeks of pregnancy. At each visit, the blood pressure was measured and the maternal cardiovascular system was assessed using transthoracic echocardiography. Two-dimensional speckle tracking was performed to assess the global longitudinal and circumferential strain on a subset of patients (15 in each group). Offline analysis was performed according to the European and American echocardiography guidelines. Multilevel linear mixed-effect models were used for all the comparisons., Results: Compared with the no-surgery group, women with previous bariatric surgery, had lower systolic and diastolic blood pressure, heart rate, and cardiac output across all the trimesters (P<.01 for all comparisons), with an evidence of more favorable diastolic indices, including a higher E-wave/A-wave ratio across the mitral valve (P<.001), higher mitral velocity at the lateral and medial annulus (E') (P=.01 and P=.03, respectively), and a lower left atrial volume (P<.05). Furthermore, women with previous bariatric surgery demonstrated lower global longitudinal (P<.01) and circumferential strain (P=.02), which is suggestive of better systolic function., Conclusion: Our findings indicate better cardiovascular adaptation to pregnancy in women with previous bariatric surgery than in pregnant women of a similar early-pregnancy body mass index but no history of surgery., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Introduction: Obesity rates have reached an epidemic level and bariatric surgery is the most effective method of sustainable weight loss. Pregnancy following bariatric surgery is associated with an increased prevalence of small babies. The objective of the study is to compare the fetal fat distribution, as assessed by fractional arm and thigh volume using three-dimensional ultrasonography, in pregnancies following maternal bariatric surgery with those without such history., Material and Methods: This is a prospective, longitudinal, observational study conducted in a Maternity Unit in the UK. The study included 189 pregnant women; 63 with previous bariatric surgery [27 restrictive (13 with gastric band, 14 with sleeve gastrectomy) and 36 malabsorptive procedures] and 126 with no previous surgery but similar maternal booking body mass index. Fetal arm and thigh volume were obtained at 30-33 and 35-37 weeks' gestation and fractional limb volumes were calculated using a commercially available software. Women underwent a 75 g, 2 h oral glucose tolerance test at 28-31 weeks of gestation., Results: Overall, adjusted fetal arm and thigh volume were smaller in the post-bariatric, compared to the no surgery, group and this was more marked in women who had undergone a previous sleeve gastrectomy (P < .001 and P = .002, respectively) or a malabsorptive procedure (P < .001 for both). There was a strong positive correlation between maternal fasting/post-prandial (2 h) glucose levels, at the time of the oral glucose tolerance test, and arm and thigh volume at both 30-33 and 35-37 weeks (P < .01 for all)., Conclusions: The study has demonstrated that in the third trimester of pregnancy, fetuses of women with previous bariatric surgery have smaller fractional limb volumes, therefore less soft tissue, compared to fetuses of women without such surgery and this may be related to the lower maternal glucose levels seen in the former pregnancies., (© 2020 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development., Design: A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed., Results: Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p- cresol sulfate, indoxyl sulfate and p- hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight., Conclusion: Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: An increasing number of women present pregnant having undergone bariatric surgery, a popular treatment for sustainable weight loss. The aim of the study was to investigate the effect, if any, of bariatric surgery on maternal and neonatal insulin resistance (IR) and neonatal body fat composition., Methods: Maternal IR, at 28 weeks of gestation during 2-hour 75 g oral glucose tolerance test (OGTT), neonatal IR, from umbilical cord venous blood, and neonatal birthweight and body fat composition (calculated by measuring skin folds) at birth were evaluated in 41 post-bariatric and 82 pregnant women with similar early pregnancy body mass index but no history of such surgery. Insulin resistance was assessed using the homeostasis model assessment of IR (HOMA-IR)., Results: In the post-bariatric surgery group, compared to the no surgery group, maternal HOMA-IR (1.15 [1.04-2.07] vs 2.20 [1.53-3.38]; p < 0.01), neonatal birthweight (p < 0.01) and body fat (p < 0.01) were significantly lower whereas neonatal cord HOMA-IR was similar (1.29 [0.65-2.39] vs 1.19 [0.46-1.93]; p = 0.49). In the no surgery group, there was a positive correlation between maternal and neonatal HOMA-IR (p = 0.03) and between neonatal HOMA-IR and body fat (p < 0.01). However, no such significant correlations were detected in the post-bariatric surgery group., Conclusion: Pregnancy following bariatric surgery is associated with a reduction in maternal IR and altered neonatal body composition with significantly lower birthweight and adiposity but no improvement in cord IR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

L-Arginine (Arg) is the enzymatic precursor of nitric oxide (NO) which has multiple biological functions. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of NO. We hypothesized that the ADMA and SDMA have additional biological functions in pregnancy, beyond NO synthesis, and may play a role in the regulation of birthweight (BW). To investigate this issue, we measured the plasma concentration of ADMA, SDMA, Arg and the NO metabolites nitrite and nitrate, at 23-25 weeks of gestation in women with normal placental function (Group 1) and in women with impaired placental perfusion; 19 of these women had normal outcome (Group 2), 14 had a fetus that was growth restricted (Group 3), and 10 women eventually developed preeclampsia (Group 4). BW percentile was found to inversely correlate with maternal plasma ADMA concentration in Group 3 (r = - 0.872, P < 0.001) and in Group 4 (r = - 0.800, P < 0.05). But, BW percentile did not correlate with the maternal plasma concentration of Arg, SDMA, nitrate or nitrite. Our results suggest that maternal plasma ADMA concentration is an important indicator of fetal growth restriction in women with impaired placental perfusion independent of NO.

Background: Birth weight, a marker of the intrauterine environment, has been extensively studied in epidemiological research in relation to subsequent health and disease. Although numerous meta-analyses have been published examining the association between birth weight and subsequent health-related outcomes, the epidemiological credibility of these associations has not been thoroughly assessed. The objective of this study is to map the diverse health outcomes associated with birth weight and evaluate the credibility and presence of biases in the reported associations., Methods: An umbrella review was performed to identify systematic reviews and meta-analyses of observational studies investigating the association between birth weight and subsequent health outcomes and traits. For each association, we estimated the summary effect size by random-effects and fixed-effects models, the 95 % confidence interval, and the 95 % prediction interval. We also assessed the between-study heterogeneity, evidence for small-study effects and excess significance bias. We further applied standardized methodological criteria to evaluate the epidemiological credibility of the statistically significant associations., Results: Thirty-nine articles including 78 associations between birth weight and diverse outcomes met the eligibility criteria. A wide range of health outcomes has been studied, ranging from anthropometry and metabolic diseases, cardiovascular diseases and cardiovascular risk factors, various cancers, respiratory diseases and allergies, musculoskeletal traits and perinatal outcomes. Forty-seven of 78 associations presented a nominally significant summary effect and 21 associations remained statistically significant at P < 1 × 10 -6 . Thirty associations presented large or very large between-study heterogeneity. Evidence for small-study effects and excess significance bias was present in 13 and 16 associations, respectively. One association with low birth weight (increased risk for all-cause mortality), two dose-response associations with birth weight (higher bone mineral concentration in hip and lower risk for mortality from cardiovascular diseases per 1 kg increase in birth weight) and one association with small-for-gestational age infants with normal birth weight (increased risk for childhood stunting) presented convincing evidence. Eleven additional associations had highly suggestive evidence., Conclusions: The range of outcomes convincingly associated with birth weight might be narrower than originally described under the "fetal origin hypothesis" of disease. There is weak evidence that birth weight constitutes an effective public health intervention marker.

Background: Insulin-like growth factors 1 and 2 (IGF1 and IGF2) and their binding proteins (IGFBPs) are expressed in the placenta and known to regulate fetal growth. DNA methylation is an epigenetic mechanism which involves addition of methyl group to a cytosine base in the DNA forming a methylated cytosine-phosphate-guanine (CpG) dinucleotide which is known to silence gene expression. This silences gene expression, potentially altering the expression of IGFs and their binding proteins. This study investigates the relationship between DNA methylation of components of the IGF axis in the placenta and disorders in fetal growth. Placental samples were obtained from cord insertions immediately after delivery from appropriate, small (defined as birthweight <10th percentile for the gestation [SGA]) and macrosomic (defined as birthweight > the 90th percentile for the gestation [LGA]) neonates. Placental DNA methylation, mRNA expression and protein levels of components of the IGF axis were determined by pyrosequencing, rtPCR and Western blotting., Results: In the placenta from small for gestational age (SGA) neonates (n = 16), mRNA and protein levels of IGF1 were lower and of IGFBPs (1, 2, 3, 4 and 7) were higher (p < 0.05) compared to appropriately grown neonates (n = 37). In contrast, in the placenta from large for gestational age (LGA) neonates (n = 20), mRNA and protein levels of IGF1 was not different and those of IGFBPs (1, 2, 3 and 4) were lower (p < 0.05) compared to appropriately grown neonates. Compared to appropriately grown neonates, CpG methylation of the promoter regions of IGF1 was higher in SGA neonates. The CpG methylation of the promoter regions of IGFBP1, IGFBP2, IGFBP3, IGFBP4 and IGFBP7 was lower in the placenta from SGA neonates as compared to appropriately grown neonates, but was unchanged in the placenta from LGA neonates., Conclusions: Our results suggest that changes in CpG methylation contribute to the changes in gene expression of components of the IGF axis in fetal growth disorders. Differential methylation of the IGF1 gene and its binding proteins is likely to play a role in the pathogenesis of SGA neonates.

Objective: To investigate the relation between first-trimester fetal growth discrepancy, as assessed by crown-rump length (CRL) at 11+0 to 13+6 weeks of gestation, and subsequent development of preeclampsia (PE) in dichorionic diamniotic (DCDA) twin pregnancies. The association between inter-twin CRL and birth weight (BW) discrepancy was also investigated., Methods: This was a retrospective, case-control study of DCDA twin pregnancies. Inter-twin CRL discrepancy was calculated as 100×(larger CRL-smaller CRL)/larger CRL. BW discordance was calculated as 100×(larger BW-smaller BW)/larger BW., Results: The study included 299 DCDA pregnancies that remained normotensive and 35 that subsequently developed PE. There was no significant difference in the inter-twin CRL discrepancy between pregnancies complicated by PE and those that were not [3.2%, interquartile range (IQR): 0.5-4.5% vs. 3.3%, IQR: 1.4-5.5%; P=0.17]. There was a positive correlation between inter-twin CRL and BW discrepancy but only in pregnancies that remained normotensive (P<0.001). In women that subsequently developed PE, there was no association between inter-twin CRL and BW discordance (P=0.54)., Conclusions: In unselected DCDA twins, first-trimester CRL discrepancy is not different between pregnancies that subsequently develop PE and those that remain normotensive. Furthermore, in pregnancies that are complicated by PE, the association between inter-twin CRL and BW discrepancy appears to be lost.

Objectives: To assess first-trimester placental perfusion, reflected in the uterine artery (UtA) pulsatility index (PI), in pregnancies complicated by gestational diabetes mellitus (GDM), with or without pre-eclampsia (PE), compared with those unaffected by GDM., Methods: UtA-PI was measured at 11 + 0 to 13 + 6 weeks' gestation in 1037 singleton pregnancies that subsequently developed GDM and in 56 649 normoglycemic controls. The measured mean UtA-PI was converted to multiples of the expected normal median (MoM), corrected for maternal weight, racial origin and gestational age, and the median MoM values in the two groups were compared., Results: The incidence of PE was higher in pregnancies with GDM than in controls (4.0% vs 2.3%, respectively; P =  0.001). However, there were no significant differences in the median UtA-PI MoM between the groups (1.00 (interquartile range (IQR), 0.82-1.21) vs 1.00 (IQR, 0.81-1.21); P = 0.73). The median UtA-PI in patients who developed PE was higher than in those who did not develop PE, regardless of the development of GDM., Conclusions: First-trimester placental perfusion, as assessed by UtA Doppler examination, is not impaired in women who subsequently develop GDM. The increased prevalence of PE in women with GDM cannot be attributed to impaired placentation., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Low maternal vitamin D levels have been associated with adverse pregnancy outcome. A recent study has suggested that low maternal vitamin D levels at the time of delivery are also associated with an almost fourfold increase in caesarean section risk. The aim of the present study was to investigate whether there is a difference in maternal serum 25-hydroxyvitamin D (25(OH)D) levels at 11-13 weeks' gestation according to the mode of delivery. Maternal serum 25(OH)D levels were measured at 11-13 weeks' gestation in 995 singleton pregnancies resulting in the birth of phenotypically normal neonates at term. The measured 25(OH)D levels were adjusted for maternal age, BMI, racial origin, smoking, method of conception and season of blood testing, and the adjusted levels (multiple of the median; MoM) were compared between those who subsequently delivered vaginally and those that delivered by caesarean section. Delivery was vaginal in 79·6 % of cases, by emergency caesarean section in 11·6 % and by elective caesarean section in 8·8 %. The median 25(OH)D level in our population was 46·82 (interquartile range (IQR) 27·75-70·13) nmol/l. The adjusted maternal median 25(OH)D levels in the emergency and elective caesarean section groups (0·99, IQR 0·71-1·46 MoM and 0·96, IQR 0·73-1·27 MoM, respectively) were not significantly different from the vaginal delivery group (0·99, IQR 0·71-1·33 MoM; P = 0·53 and P = 0·81, respectively). First-trimester maternal serum 25(OH)D levels are similar between women who subsequently have a vaginal delivery and those who deliver by elective or emergency caesarean section.

Objective: To investigate whether the sonographic and maternal serum biochemical markers used in first-trimester screening for chromosomal abnormalities are altered in pregnancies affected by maternal HIV infection., Design: Nested case-control study., Setting: Routine antenatal visit in a teaching hospital., Population: Ninety HIV-positive and 450 HIV-negative pregnant women., Methods: Findings from first-trimester antenatal visit for calculation of the risk for chromosomal abnormalities were compared between HIV-positive (treated and untreated) and HIV-negative women., Main Outcome Measures: First-trimester maternal serum free β human chorionic gonadotrophin (free β-hCG) pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness (NT), were compared., Results: There were no statistically significant differences between the HIV-positive and HIV-negative women in the median maternal levels of free β-hCG, PAPP-A and fetal NT. However, within the HIV-positive group those receiving antiretroviral treatment (n = 41) had a significantly lower median multiple of the median (MoM) for free β-hCG (0.74, interquartile range [IQR] 0.45-1.32 MoM) than HIV-positive women on no treatment (1.03, IQR 0.76-1.85 MoM; P = 0.006) and HIV-negative women (1.0, IQR 0.68-1.47 MoM; P = 0.003). There was no correlation between the level of free β-hCG or PAPP-A and maternal viral load or CD4(+) count., Conclusions: Maternal levels of free β-hCG in treated HIV-positive pregnant women were lower compared with those in non-treated HIV-positive and HIV-negative women, whereas the PAPP-A levels and fetal NT remained unaltered., (© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.)

Background/objectives: Pre-eclampsia (PE) is associated with profound changes in the maternal cardiovascular system. The aim of the present study was to assess whether alterations in the maternal arterial stiffness precede the onset of PE in at risk women., Methodology/principal Findings: This was a cross sectional study involving 70 pregnant women with normal and 70 women with abnormal uterine artery Doppler examination at 22-24 weeks of gestation. All women had their arterial stiffness (augmentation index and pulse wave velocity of the carotid-femoral and carotid-radial parts of the arterial tree) assessed by applanation tonometry in the second trimester of pregnancy, at the time of the uterine artery Doppler imaging. Among the 140 women participating in the study 29 developed PE (PE group) and 111 did not (non-PE group). Compared to the non-PE group, women that developed PE had higher central systolic (94.9 ± 8.6 mmHg vs 104.3 ± 11.1 mmHg; p  =  < 0.01) and diastolic (64.0 ± 6.0 vs 72.4 ± 9.1; p < 0.01) blood pressures. All the arterial stiffness indices were adjusted for possible confounders and expressed as multiples of the median (MoM) of the non-PE group. The adjusted median augmentation index was similar between the two groups (p  =  0.84). The adjusted median pulse wave velocities were higher in the PE group compared to the non-PE group (carotid-femoral: 1.10 ± 0.14 MoMs vs 0.99 ± 0.11 MoMs; p < 0.01 and carotid-radial: 1.08 ± 0.12 MoMs vs 1.0 ± 0.11 MoMs; p < 0.01)., Conclusions/significance: Increased maternal arterial stiffness, as assessed by pulse wave velocity, predates the development of PE in at risk women.

Objective: We sought to investigate whether maternal arterial stiffness is altered in pregnant women with gestational diabetes mellitus (GDM) and type 2 diabetes compared to normoglycemic women., Study Design: We conducted a cross-sectional study involving 34 women with GDM and their controls (n = 34), and 34 women with type 2 diabetes and their controls (n = 34). Maternal arterial stiffness was assessed using applanation tonometry., Results: In patients with GDM, compared to their controls, augmentation index (a measure of arterial wave reflection) was higher (13.1 +/- 8.9% vs 0.7 +/- 11.4%; P < .001) and pulse wave velocity (PWV) (arterial stiffness of the carotid-femoral) was marginally increased (6 +/- 1.5 vs 5.4 +/- 0.6 m/s; P = .07). In type 2 diabetics, compared to their controls, both augmentation index and PWV were increased (11.5 +/- 11.4% vs 3.3 +/- 12.5%; P = .006, and 6.8 +/- 1.2 vs 5.6 +/- 1 m/s; P < .001). When all groups were considered together, there was a significant trend of increasing augmentation index (P = .001) and PWV (P < .001) from controls to those with GDM to type 2 diabetes., Conclusion: Pregnancies complicated by GDM and type 2 diabetes are associated with increased maternal arterial stiffness., (Copyright 2010 Mosby, Inc. All rights reserved.)

Aim: There is little information about maternal central haemodynamics and arterial stiffness in pregnancies affected by Type 1 diabetes mellitus. The aim of the current study was to investigate whether maternal arterial stiffness is altered in pregnant women with Type 1 diabetes mellitus compared with women with uncomplicated pregnancies., Methods: This was a cross-sectional study involving 37 pregnant women without diabetes and 37 pregnant women with Type 1 diabetes mellitus during the second trimester of pregnancy. Maternal wave reflection (augmentation index) and pulse wave velocity of the carotid-femoral and carotid-radial part of the arterial tree were assessed non-invasively using applanation tonometry., Results: Pregnant women with normal pregnancies and Type 1 diabetes mellitus had similar augmentation index (3.7 +/- 12.8 vs. 5.1 +/- 12.6%, P = 0.6), even after adjusting for possible confounders. Within the group of diabetic women, augmentation index was associated with duration of diabetes (P = 0.003, r(2) = 0.22) but not with glycated haemoglobin. Pulse wave velocities were similar between the two groups of women (carotid-femoral: 5.6 +/- 0.9 vs. 5.7 +/- 1.1 m/s, P = 0.4; carotid-radial: 7.4 +/- 1.2 vs. 7.8 +/- 1 m/s, P = 0.1). In the diabetic women there was no significant association between the pulse wave velocities and either duration of diabetes or glycated haemoglobin., Conclusions: Pregnancy in women with Type 1 diabetes mellitus is not associated with altered maternal systemic arterial stiffness. However, maternal wave reflections increase with the duration of diabetes.

Preeclampsia (PE) is characterized by an aberrant maternal cardiovascular adaptation to pregnancy and increased cardiovascular risk later on in life. The aim of this study was to compare the maternal wave reflections and arterial stiffness in women with established PE and those with normotensive pregnancies, after systematic adjustment for known confounders. This was a cross-sectional study involving 69 normotensive, pregnant women and 54 women with established PE. Maternal wave reflection (augmentation index) and pulse wave velocity of the carotid-radial and carotid-femoral parts of the arterial tree were assessed noninvasively using applanation tonometry. The measurements were adjusted for maternal age, heart rate, mean arterial pressure, and aortic time to wave reflection and expressed as multiples of the median (MoM) of the control group. In the PE group, compared with controls, there was an increase in the median pulse wave velocity of both the carotid to femoral [1.1, interquartile rage (IQR) 1.0-1.3 MoM vs. 0.9, IQR 0.9-1.0 MoM; P < 0.0001] and carotid to radial (1.0, IQR 0.9-1.1 MoM vs. 0.9, IQR 0.9-1.0 MoM; P = 0.01) parts of the arterial tree. In contrast, there were no significant differences between the two groups in the median augmentation index (0.9, IQR 0.7-1.1 MoM vs. 1.0, IQR 0.5-1.8 MoM; P = 0.46). In conclusion, we found that established PE is characterized by increased maternal arterial stiffness but not altered maternal wave reflection.

Objective: To compare urinary placental growth factor (PlGF) concentration at 11(+0) to 13(+6) weeks of gestation in women who subsequently develop pre-eclampsia with normotensive controls., Design: Nested case-control study within a prospective study for first trimester prediction of pre-eclampsia., Setting: Routine antenatal visit in a teaching hospital., Population: Fifty-two women who developed pre-eclampsia and 52 controls matched for gestational age and sample storage time., Methods: Urinary PlGF concentration and PlGF to creatinine ratio were measured in women who developed pre-eclampsia and their matched controls. Comparisons between groups were performed using Student's t test., Main Outcome Measures: Development of pre-eclampsia., Results: In the pre-eclampsia group, the median urinary PlGF concentration (20.6 pg/ml, interquartile range [IQR] 9.1-32.0 pg/ml) and median urinary PlGF to creatinine ratio (1.6 pg/mg, IQR 1.2-2.5 pg/mg) were not significantly different from the control group (11.8 pg/ml, IQR 5.5-29.8 pg/ml, P=0.1 and 1.7 pg/mg, IQR 1.2-2.3 pg/mg, P=0.3, respectively). There were no significant differences between women with early-onset pre-eclampsia requiring delivery before 34 weeks (n=13) and those with late-onset pre-eclampsia (n=39) and between women with pre-eclampsia and fetal growth restriction (FGR) (n=25) and those with pre-eclampsia and no FGR (n=27) in either median PlGF concentration or median urinary PlGF to creatinine ratio., Conclusions: The development of pre-eclampsia is not preceded by altered urinary PlGF concentration in the first trimester of pregnancy.

Objectives: To determine whether maternal serum concentrations of placental growth factor (PlGF) and soluble endoglin (sEng) are altered in women who subsequently develop pre-eclampsia (PE) or have small-for-gestational-age (SGA) infants, and whether these changes are associated with maternal endothelial dysfunction., Methods: Maternal serum PlGF and sEng were measured in two groups of pregnant women at 23-25 weeks' gestation: Group A (n = 40), with normal uterine artery Doppler waveforms and Group B (n = 43) with abnormal Doppler. Maternal endothelial dysfunction was assessed by flow-mediated dilatation (FMD) of the brachial artery. Comparisons between groups were performed using one-way analysis of variance., Results: In Group B, 16 women had normal outcome, 15 delivered SGA infants and 12 developed PE. Women who developed PE had lower levels of PlGF (154.8 +/- 150.8 vs. 423.3 +/- 230.5 pg/mL; P < 0.001) (data given as mean +/- SD) and higher levels of sEng (8.1 (7.0-14.1) vs. 6.5 (4.9-7.9) pg/mL; P < 0.05) (data given as median (interquartile range)) than Group A. Similar were the findings in women who delivered SGA infants. In women who subsequently developed PE, there was no correlation between FMD and either PlGF or sEng., Conclusions: Maternal serum concentrations of PlGF and sEng are altered in women who develop PE. However, these alterations do not correlate directly with maternal endothelial dysfunction., ((c) 2008 ISUOG.)

Adiponectin and leptin, two adipose-tissue-derived proteins, have been reported to be elevated in women with established PE (pre-eclampsia). The aim of the present study was to investigate whether alterations in adiponectin and leptin levels predate the development of PE and FGR (fetal growth restriction) in women at increased risk of these complications, as assessed by Doppler examination of the uterine arteries during the second trimester of pregnancy. We also sought to investigate the circulating levels of adiponectin and leptin in women with established severe early-onset FGR. The study included three groups of pregnant women at 23-25 weeks: Group A (n=44) with normal uterine artery Doppler waveforms, Group B (n=49) with abnormal Doppler waveforms and normal fetal growth at the time of the examination, and Group C (n=15) with established severe FGR and abnormal Doppler waveforms. All women had plasma adiponectin and leptin measured by sensitive immunoassays. In Group B, 19 women had a normal outcome, 17 delivered infants with FGR and 13 developed PE. The women who developed PE delivered smaller babies earlier than women with a normal outcome (P<0.001). There were no significant differences in adiponectin levels between any of the groups (overall P=0.3). Leptin concentrations, expressed as MoM (multiples of the median) of Group A, were higher in women in Group C, i.e. established severe FGR at 2.5 (1.2-2.7) MoMs (overall P<0.001), compared with all of the other groups and subgroups. In conclusion, we found that, in pregnancies complicated by severe early-onset FGR, the maternal plasma concentration of leptin is twice as high as in normal pregnancies. However, the second trimester levels of maternal plasma adiponectin and leptin in pregnancies that subsequently develop PE and/or FGR are not significantly different from normal and, consequently, it is unlikely that these markers will be useful as predictors of these pregnancy complications.

Objective: The objective of the study was to determine the levels of circulating endothelial progenitor cells (EPCs), which are peripheral blood mononuclear cells (PBMNCs) that contribute to vascular repair in normal pregnancy., Study Design: The concentration of EPCs in maternal blood was measured in healthy nonpregnant women (group A, n = 8), normal singleton pregnancies (group B, n = 24), and normal twin pregnancies (group C, n = 21)., Results: In group A, the mean (SD) level of EPCs was 77.0% (8.6%) adherent PBMNCs. In group B, the mean level was lower than in group A and decreased with gestation from 61.3% (14.9%) in the first trimester to 56.0% (16.2%) in the second trimester and 52.0% (8.7%) in the third trimester (P = .001). Similarly, the level of EPCs in group C was lower than in group A and decreased with gestation from 64.6% (9.6%) in the first trimester to 65.2% (12.7%) in the second trimester and 56.4% (12.6%) in the third trimester (P = .002)., Conclusion: Normal pregnancy is associated with a decrease in maternal circulating levels of EPCs.

Normal pregnancy is associated with profound alterations in the maternal cardiovascular system. The aim of the present study was to assess noninvasively, using applanation tonometry, the maternal central aortic blood pressures (BP), effects of wave reflection and arterial stiffness (aortic and brachial pulse wave velocity) in normal pregnancy. This was a cross sectional study including 193 women with normal singleton pregnancies at 11 to 41 weeks of gestation and 23 nonpregnant controls, matched for age and height. Compared to nonpregnant controls, pregnant women had lower mean arterial pressure (85+/-8.9 mm Hg versus 81.1+/-7.2 mm Hg; P=0.01), central systolic BP (103+/-11 mm Hg versus 96+/-8 mm Hg, P=0.001), central diastolic BP (71+/-9 mm Hg versus 67+/-7 mm Hg, P=0.008), and augmentation index (AIx) (19+/-11% versus 4+/-12%, P<0.001). The AIx changed significantly with gestation reaching its nadir at midpregnancy (R(2)=0.05, P=0.007). This change was present even after adjusting for maternal age (P<0.001), heart rate (P<0.001), and mean arterial BP (P<0.001); known determinants of AIx. The pulse wave velocity (carotid-radial and carotid-femoral) did not change significantly with gestation and was marginally different between pregnant and nonpregnant women (P=0.03 and P=0.05 for carotid-radial and carotid-femoral respectively). However, adjustments for maternal age and mean arterial pressure rendered these differences nonsignificant (P=0.2 for carotid-radial, P=0.5 for carotid-femoral). In summary, we found that normal pregnancy is associated with a reduction in central BP and wave reflection.

Objective: To examine the distribution of placental growth factor (PlGF), vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sFlt-1) in maternal and embryonic fluid compartments in early pregnancy., Method: The concentrations of PlGF, VEGF and sFlt-1 were measured in coelomic fluid and maternal serum from 16 singleton pregnancies at 7.0-9.3 weeks. In six cases, amniotic fluid was also examined., Results: The median concentration of PlGF was 14.1 (range 8.9-27.6) pg/mL in maternal serum, 13.9 (range 9.5-31.4) pg/mL in coelomic fluid and 8.9 (range 3.9-15.3) pg/mL in amniotic fluid. The concentration of PlGF increased between 7.0 and 9.3 weeks in maternal serum (p = 0.001) and decreased in coelomic and amniotic fluid (p = 0.001). The median concentration of sFlt-1 was 8561 (range 6724-10 673) pg/mL in coelomic fluid, 523 (range 244-986) pg/mL in maternal serum, 30 (range 12-83) pg/mL in amniotic fluid (p = 0.0001), and it did not change significantly with gestation. VEGF was undetectable in most of the samples, and therefore, no further analysis was performed., Conclusion: PlGF and sFlt-1 are present in the maternal and fetal fluid compartments in very early pregnancy, and their distribution is consistent with their site of production and the local conditions of transport.

Objective: This study was undertaken to determine whether maternal serum concentration of the angiogenic factor vascular endothelial growth factor (VEGF) and its circulating antagonist, soluble fms-like tyrosine kinase 1 (sFlt-1), which have been implicated in the pathogenesis of preeclampsia (PE), are altered in pregnancies that subsequently develop PE and in those with established fetal growth restriction (FGR)., Study Design: Three groups of healthy pregnant women at 23 to 25 weeks of gestation were examined: group A (n = 42) with normal uterine artery Doppler waveforms, group B (n = 49) with abnormal uterine artery Doppler waveforms, and group C (n = 15) with abnormal Doppler results and established FGR. Comparisons between multiple groups were performed by using 1-way analysis of variance or Kruskal-Wallis test., Results: In group C, compared with group A, the median sFlt-1 was significantly higher (P < .0001) and VEGF was lower (P < .001). Group C included 3 women who had PE develop. In group B, 19 women had a normal outcome, 13 had PE develop, and 17 had FGR develop. There were no significant differences in sFlt-1 levels between any of the subgroups of group B and group A., Conclusion: Maternal serum concentration of sFlt-1 in pregnancies with FGR is increased but this increase is not evident in pregnancies with impaired placentation that subsequently had either FGR or PE develop.

Background: Pre-eclampsia is thought to have an important genetic component. Recently, pre-eclampsia has been associated in some studies with carriage of a common eNOS gene Glu298Asp polymorphism, a variant that leads to the replacement of glutamic acid by aspartic acid at codon 298., Method: Healthy women with singleton pregnancies were recruited from 7 district general hospitals in London, UK. Women at high risk of pre-eclampsia were screened by uterine artery Doppler velocimetry at 22-24 weeks of gestation and maternal blood was obtained to genotype the eNOS Glu298Asp polymorphism. Odds ratios (OR) and 95%CI, using logistic regression methods, were obtained to evaluate the association between the Glu298Asp polymorphism and pre-eclampsia. A meta-analysis was then undertaken of all published studies up to November 2005 examining the association of eNOS Glu298Asp genotype and pre-eclampsia., Results: 89 women with pre-eclampsia and 349 controls were included in the new study. The Glu298Asp polymorphism in a recessive model was not significantly associated with pre-eclampsia (adjusted-OR: 0.83 [95%CI: 0.30-2.25]; p = 0.7). In the meta-analysis, under a recessive genetic model (1129 cases & 2384 controls) women homozygous for the Asp298 allele were not at significantly increased risk of pre-eclampsia (OR: 1.28 [95%CI: 0.76-2.16]; p = 0.34). A dominant model (1334 cases & 2894 controls) was associated with no increase of risk of pre-eclampsia for women carriers of the Asp298 allele (OR: 1.12 [95%CI: 0.84-1.49]; p = 0.42)., Conclusion: From the data currently available, the eNOS Glu298Asp polymorphism is not associated with a significant increased risk of pre-eclampsia. However, published studies have been underpowered, much larger studies are needed to confirm or refute a realistic genotypic risk of disease, but which might contribute to many cases of pre-eclampsia in the population.

Objective: Pregnancy at high altitude has been associated with increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on endothelial function during pregnancy as assessed by a non-invasive method., Design: Cross-sectional study., Setting: Two maternity units providing routine antenatal care: one at high altitude (District General Hospital--IPSS in Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru)., Population: Sixty pregnant women at 6-42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively., Methods: Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution ultrasound., Main Outcome Measures: Differences in flow mediated dilatation of the brachial artery in two groups of pregnant women, one at high altitude and one at sea level., Results: Both at high altitude and sea level flow-mediated dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls. However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59% lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance., Conclusion: These data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the brachial artery, is not impaired.

Objective: To investigate whether a maternal inflammatory response precedes the development of preeclampsia., Design: Cross-sectional study., Setting: Antenatal clinic in an inner city teaching hospital., Population: Two groups of women were examined at 23-25 weeks of gestation. The first group (45 women) had normal uterine artery Doppler waveforms and subsequently had a normal pregnancy outcome. The second group (45 women) had Doppler evidence of impaired placental perfusion and 21 (47%) of them had normal outcome, 14 (31%) developed intrauterine growth restriction and 10 (22%) developed pre-eclampsia, with or without intrauterine growth restriction., Methods: C-reactive protein, an acute-phase reactant, was measured in maternal serum using a highly sensitive method with a detection limit of 0.05 mg/L., Main Outcome Measures: Development of pre-eclampsia, as defined by the International Society for the Study of Hypertension in Pregnancy. Intrauterine growth restriction was defined as birthweight <5th centile for gestation and sex of the neonate., Results: The serum C-reactive protein concentration in women who subsequently developed pre-eclampsia (median 1.56, range 0.55-3.12 mg/L) or delivered a baby with birthweight <5th centile (median 0.74, range 0.64-1.58 mg/L) was not significantly different from that in women with uncomplicated pregnancies (median 1.28, range 0.75-2.08 mg/L; P = 0.95 and P = 0.62, respectively)., Conclusion: These findings suggest that the onset of clinical signs of pre-eclampsia may not be preceded by a maternal inflammatory response, as assessed by measurement of C-reactive protein.

Objective: The purpose of this study was to investigate the vascular function of pregnant women with insulin-dependent diabetes mellitus, using a noninvasive method., Study Design: This was a cross-sectional study that examined vascular function, which was assessed by flow-mediated dilatation of the brachial artery, in 37 pregnant women with insulin-dependent diabetes mellitus and in 37 healthy pregnant women at 20 weeks of gestation. The control of diabetes was also assessed by the measurement of glycosylated hemoglobin. Data were analyzed by 2-sided unpaired t test and multivariate regression analysis., Results: In the pregnant women with insulin-dependent diabetes mellitus, flow-mediated dilatation of the brachial artery was significantly lower than in healthy pregnant women (6.43% +/- 3.66% vs 9.43% +/- 3.69%, respectively; P =.0008). This difference was apparent even after an adjustment was made for blood vessel diameter, which was different between the 2 populations (P =.01). Flow-mediated dilatation in diabetic women was significantly correlated with the duration of diabetes (P =.01) but not with the levels of glycosylated hemoglobin., Conclusion: Maternal insulin-dependent diabetes mellitus is associated with an impaired vasodilatory response to a blood flow stimulus. This vascular dysfunction is associated with the duration of the diabetes.

A common polymorphism of the endothelial NO synthase gene that predicts a Glu298Asp amino acid substitution in the mature protein has been associated with cardiovascular disorders in which NO bioactivity is impaired. However, the influence of this polymorphism on endothelial function is unknown. Healthy pregnancy is associated with enhanced endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery, a response mediated by NO. In this study, we investigated the effect of the endothelial NO synthase Glu298Asp polymorphism on endothelium-dependent vasodilation in early pregnancy, making the hypothesis that any genotype-dependent differences in NO generation would be more marked during pregnancy, when the production of NO is upregulated. FMD of the brachial artery was recorded during the first trimester in 139 healthy women with normal singleton pregnancies genotyped for the Glu298Asp variant of endothelial NO synthase. Maternal FMD exhibited a codominant inverse relation with the number of Asp298 alleles (r=-0.21, P=0.01). Among homozygotes for endothelial NO synthase Asp298, FMD (7.99+/-1.46%) was significantly lower than that observed among individuals homozygous for endothelial NO synthase Glu298 (10.12+/-3.44) (P=0.002). In a backward stepwise multiple regression analysis, vessel size (P<0.0001) and Glu298Asp polymorphism (P=0.01) were significantly and independently correlated with FMD. Our findings indicate that the endothelial NO synthase Glu298Asp polymorphism is associated with differences in endothelium-dependent dilation at 12-week gestation and are the first to implicate genetic factors in the normal vascular adaptation to pregnancy. They also provide a potential mechanism linking the endothelial NO synthase polymorphism with the development of cardiovascular disorders and have implications for understanding the genetic basis of preeclampsia.

Objective: To determine whether the incidence of pre-eclampsia is different in dichorionic compared to monochorionic twin pregnancies., Methods: The study involved 666 twin pregnancies resulting in two live births after 24 weeks of gestation. Ultrasound examination at 10-14 weeks of gestation demonstrated that 171 (25.7%) were monochorionic and 495 (74.3%) were dichorionic twins. Pregnancy outcome information regarding the development of pre-eclampsia was obtained from the maternity units. The incidence of pre-eclampsia in the dichorionic and monochorionic twin pregnancies was compared., Results: The incidence of pre-eclampsia in monochorionic twin pregnancies (9.4%) was not significantly different from that in dichorionic pregnancies (7.3%) ( P = 0.48). Multiple logistic regression revealed that chorionicity has no effect on the development of pre-eclampsia after adjusting for maternal age, ethnic group, maternal smoking, parity and gestational age at delivery ( P = 0.6; odds ratio for monochorionic compared with dichorionic twin pregnancies, 1.19; 95% confidence interval, 0.61-2.3)., Conclusion: In twin pregnancies chorionicity does not affect the incidence of pre-eclampsia.

Objective: To assess the maternal endothelial function in normal twin pregnancy., Design: Cross-sectional study., Subjects: Endothelial function was investigated in 74 women with normal twin pregnancy at 11-30 weeks of gestation and the results were compared to previous reported findings in 98 women with normal singleton pregnancy and 19 non-pregnant controls., Methods: Endothelial function was assessed by measuring the changes of the brachial artery diameter in response to reactive hyperemia (flow-mediated dilatation) using external high resolution ultrasound., Results: Flow-mediated dilatation of the brachial artery in both twin and singleton pregnancies was significantly higher than in non-pregnant women (P = 0.002 and P = 0.02, respectively). However, there was no significant difference in flow-mediated dilatation between women with twin and singleton pregnancy (9.61 +/- 4.36 vs. 8.84 +/- 3.18, P = 0.38). Resting vessel size, baseline flow and reactive hyperemia did not change significantly with gestation in twin pregnancy and were similar to values in singleton pregnancies and controls., Conclusion: Our findings indicate that although in pregnancy endothelial function is enhanced, this change may not be affected by the number of fetoplacental units present.

Objective: To assess endothelial function in normal pregnancy by non-invasive methods., Methods: Flow-mediated dilatation of the brachial artery was measured by ultrasonography in 157 women with normal singleton pregnancies between 10 and 40 weeks' gestation and 19 non-pregnant controls., Results: Flow-mediated dilatation in the non-pregnant controls was 6.42 +/- 2.45%. In pregnant women, between 10 and 30 weeks, the mean flow-mediated dilatation (8.84 +/- 3.18%) was significantly higher than the non-pregnant controls (P = 0.002), but after 30 weeks of gestation there was a decrease to prepregnancy levels. Resting vessel diameter and blood flow were significantly increased in pregnancy, mainly after 30 weeks' gestation (P < 0.001, P < 0.001, respectively). Flow-mediated dilatation was significantly correlated to resting vessel diameter and reactive hyperemia., Conclusion: Normal pregnancy is associated with enhanced endothelial function which is apparent from at least 10 weeks' gestation.