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Background Pregnant women experience numerous physiological and biomechanical alterations which may be associated with their increased risk of experiencing a fall. Gait alterations in other populations who fall include increased step width and mediolateral trunk motion. It is not known if pregnant women who have fallen exhibit these alterations. Research question Our purpose was to examine torso kinematics and step width during gait in pregnant fallers, pregnant non-fallers and non-pregnant controls. We also examined trunk anthropometry in the pregnant groups to determine if pregnant fallers have different trunk physiques than pregnant non-fallers. Methods 3D kinematic data were collected on 14 pregnant fallers, 15 pregnant non-fallers and 40 non-pregnant controls. Pregnant women were in their second or third trimester of pregnancy. Frontal plane translations of C7 and L4, step width, stride length, walking velocity, and 3D thoracic and pelvic kinematics were determined. Anthropometric torso measurements were obtained on the pregnant women. A series of MANCOVAs was performed (covariate: walking velocity, α = 0.05) to compare the dependent variables between pregnant fallers, pregnant non-fallers, and controls. Tukey post-hoc analyses were performed when appropriate (α = 0.05). A MANOVA compared anthropometric variables between pregnant fallers and non-fallers (α = 0.05). Results Pregnant non-fallers exhibited greater step width and frontal and transverse plane angles at heel contact and range of motion over the gait cycle when compared to the fallers. Trunk anthropometry did not differ between pregnant fallers and non-fallers. Significance Pregnancy-associated gait alterations differed between fallers and non-fallers. Greater step width of the pregnant non-fallers increased the base of support, thus increasing stability. Exercise participation may allow pregnant women to better adapt to their altered physiques and be more able to prevent a fall should a trip or slip occur.

Although pregnant women are anecdotally said to "waddle" during gait, researchers have not quantified the kinematics of these gait alterations. The purpose of this study was to examine the effects of pregnancy on thoracic and pelvic kinematics during gait.Data were collected on 29 pregnant subjects in the mid-second and third trimesters and on 40 control women. Three-dimensional kinematic data were collected on subjects walking at their freely-chosen speed. Right foot heel-strike (RHS) and left foot toe-off (LTO) were determined from force plate data. Thoracic and pelvic angles at RHS, step width, mediolateral translation of the C7 and L4 vertebrae, and the ranges of motion (ROMs) of the thorax and pelvis over the gait stride were determined. A series of MANCOVAs were performed with trimester (second, third, and control) as the independent variable and velocity as the covariate (α=0.05). Post-hoc analyses were performed when appropriate.Increased lateral translation of the C7 and L4 vertebrae (third trimestersecond trimestercontrol, p0.05) was noted, accompanied by an increased step width in the third trimester (p=0.03). At heel strike, pregnant women had greater thoracic extension (third trimestersecond trimestercontrol, p0.05) and greater anterior pelvic tilt (third trimestercontrol; p0.05). Sagittal plane thoracic ROM was less in the third trimester compared to controls (p0.01).Pregnant women demonstrated a lateral shifting of the body during gait, which accompanied a greater step width. The increased thoracic extension and anterior pelvic tilt, along with decreased sagittal plane ROM are likely adaptations to increased abdominal size.

Pregnant women experience numerous physical alterations during pregnancy which may place them at an increased risk of falls. The purpose of this study was to examine ground reaction forces (GRFs) during staircase locomotion in pregnant and non-pregnant women. Methods Data were collected on 29 pregnant women in their second and third trimesters, and on 40 control women. Subjects walked at their freely chosen speeds during stair ascent and descent. A force plate imbedded in the second stair, but structurally independent of the staircase, was used to collect GRF data (1080 Hz). A marker placed on the L3/L4 spinal segment was used to determine ascent and descent velocity from a motion-capture system. In the statistical analyses, trimester (control, second trimester, third trimester) and subject were the independent variables. Stance time and ascent/descent velocity were analyzed with an ANOVA. Mediolateral excursion of the COP during the step was analyzed with an ANCOVA. The GRFs were categorized into anterioposterior, mediolateral, and vertical forces. A two factor MANCOVA (subject, trimester) was performed on each GRF category. Mass and velocity served as covariates in each analysis (α = 0.05). Results The mediolateral excursion of the COP during ascent was greater in the third trimester (p = 0.04). The anterioposterior braking impulse was greater in both ascent (p = 0.01) and descent (p = 0.01) during pregnancy. The vertical GRF loading rate during descent was greater in pregnant women than in controls (p = 0.04). Conclusion These alterations are likely related to increased instability during stairway walking and could contribute to increased fall risk during pregnancy.

Pregnant women are at a high risk of experiencing a fall. To our knowledge, ground reaction forces (GRFs) in pregnant fallers and non-fallers have not been reported.The purpose of this study was to examine the effects of pregnancy and fall history on GRFs during walking.Forty one pregnant subjects in the mid 2nd and 3rd trimesters (pregnant fallers: n=15, pregnant non-fallers: n=14), and 40 control women walked at a freely chosen walking speed along an 8m walkway. A force plate, hidden in the walkway, was used to collect GRFs (1080Hz). Kinematic data (120Hz) were collected from a marker placed on the lumbar spine to estimate walking velocity. GRF variables included mediolateral Center of Pressure (COP) excursion, and GRFs normalized to body mass. A two factor ANOVA (trimester x fall group) was used to compare subject demographics, and walking velocity (α=0.05). A two factor ANCOVA (trimester×fall group, covariate: velocity) was performed to examine other GRF variables (Bonferroni corrected α=0.006) and the mediolateral COP excursion (α=0.05).Walking velocity was greater in the control group (p0.05). No differences were seen in the GRFs or COP movement between trimesters or between pregnant fallers and non-fallers.When walking velocity was considered in the statistical model, ground reaction forces are essentially unchanged by pregnancy.

Please cite this paper as: McCrory J, Chambers A, Daftary A, Redfern M. Dynamic postural stability in pregnant fallers and non-fallers. BJOG 2010;117:954–962. Objective To compare dynamic postural stability in pregnant women who have fallen during their pregnancies with those who have not, and with a group of non-pregnant women. Design The study was both longitudinal and cross-sectional. A cohort of pregnant women were followed through their second and third trimesters. A non-pregnant control group was used for comparison. Setting University-based laboratory. Population A total of 81 women (41 pregnant and 40 controls) participated. Twenty-nine pregnant women completed the protocol. Methods Data were collected on the pregnant women in the middle of their second and third trimesters. Pregnant women were surveyed about their daily activities, exercise participation, and fall history. Postural reaction time and centre of pressure (COP) movement data, in response to translational perturbations, were collected using a force plate. A mixed-model analysis of variants (ANOVA) was performed on each of the dependent variables (α = 0.05). Chi-square analysis was performed to determine if exercise participation altered the likelihood of a subject experiencing a fall (α = 0.05). Main outcome measures Reaction time, initial sway, total sway, and sway velocity. Results Fifty-two percent of our pregnant subjects experienced a fall. Initial sway response, total sway, and sway velocity were smaller in the pregnant fallers than in the non-fallers and control participants (P

Hypoxia-inducible transcription factor-1alpha and -2alpha (HIF-alpha) proteins and regulated genes are increased in preeclamptic (PE) placentas. Although placental hypoxia likely stabilizes HIF-alpha proteins, we previously reported that there is also a defect in oxygen-dependent reduction of HIF-alpha proteins in PE relative to normal pregnant (NP) placentas that could contribute to their over-expression. After a 4-h exposure to 2% oxygen, placental villous explants were exposed to 21% oxygen over 90 min. As assessed by Western analysis, the defective oxygen-dependent reduction of HIF-1alpha protein in villous explants from PE placenta was unaffected by the protein synthesis inhibitor, cycloheximide. However, after incubation with the proteasomal inhibitor, clasto-lactacystin, oxygen-dependent reduction of HIF-1alpha protein was markedly and similarly impaired in the villous explants from both normal and PE placentas. Thus, impairment of protein degradation rather than increased synthesis causes inadequate oxygen-dependent reduction of HIF-1alpha protein in PE placentas. Immunoprecipitation studies revealed comparable association of HIF-1alpha with von Hippel Lindau (VHL) protein in placentas from NP and PE women. Furthermore, prolyl hydroxylase-3 protein was appropriately upregulated in the PE placentas as determined by Western analysis paralleling the increases of HIF-alpha proteins. These results suggest that molecular events leading to the formation of the HIF-1alpha:VHL:ubiquitin ligase complex are most likely not impaired in PE placentas. Finally, proteasomal trypsin, chymotrypsin, and peptidyl glutamyl-like activities were significantly reduced by approximately 1/3 in PE placentas by using specific peptide substrates coupled to a fluorescent tag. Unexpectedly, however, they were even further decreased in placentas from normotensive women delivering growth restricted babies >37 weeks gestation-placentas which do not have elevated HIF-alpha proteins. In conclusion, accumulation of HIF-alpha proteins in PE placentas may occur as a consequence of both increased formation secondary to relative ischemia/hypoxia and reduced degradation after reperfusion/oxygenation consequent to proteasomal dysfunction. In contrast, in placentas from normotensive women delivering growth restricted babies >37 weeks gestation, proteasomal activity, albeit markedly reduced, is adequate to cope with degradation of HIF-alpha proteins, which have not been increased by an hypoxic environment.

BACKGROUND & AIMS: It is not clear how intake of gluten during infancy affects subsequent risk of celiac disease. We investigated whether gluten intake before 2 years of age increases risk for celiac disease in genetically susceptible children. METHODS: We performed a case-control study of 436 pairs of children, generated from a database of 2525 children with genetic susceptibility to celiac disease in Sweden, matched for sex, birth year, and HLA genotype from September 2004 and February 2010. Children were screened annually for celiac disease using an assay for tissue transglutaminase autoantibodies (tTGA). Intestinal biopsies were collected from children who tested positive for tTGA to confirm the presence of celiac disease. Gluten intake was calculated from 3-day food records collected when the children were 9, 12, 18 and 24 months old. RESULTS: Breastfeeding duration (median 32 weeks) and age at first introduction to gluten (median 22 weeks) did not differ between cases and tTGA-negative children (controls). At the visit prior to tTGA seroconversion, cases reported a larger intake of gluten (median 4.9 g/day) than controls (median 3.9 g/day) (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13-1.46; P=.0002). More cases consumed amounts of gluten in the upper 3rd tertile (i.e. >5.0 g/day) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P

Objective: To assess seasonal variability in antenatal blood pressure (BP). Methods: We studied 1919 pregnant women who contributed 21,119 antenatal BP measurements. Results: BP peaked in winter and reached a nadir in summer. After confounder adjustment, systolic BP was 1.0 to 1.7 mm Hg higher January to May, 0.6 mm Hg higher in September and October, and 0.8 mm Hg higher in November and December compared with August. After stratifying by overweight status, BP showed strong seasonal variability among lean women, whereas there were no seasonal trends among overweight women. Conclusion: Environmental factors may regulate gestational BP and may be relevant to seasonality of hypertensive disorders of pregnancy.

System A amino acid transporter activity is reduced in placentas from small-for-gestational-age (SGA) compared to normal pregnancies. We compared the expression of the system A transporters between preeclamptic and control and between small-for-gestational-age and controls pregnancies.We used placental samples from 18 preeclamptic pregnancies matched with 17 normal pregnancies and from 16 SGA pregnancies matched with 15 different normal pregnancies. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) we quantified the mRNA for two system A subtype target genes ATA1 and ATA2 as well as beta-actin for normalization.There was no significant difference of mRNA for ATA1 or ATA2 transporters between preeclamptic and their controls or SGA pregnancies and their controls.Despite previous studies reporting reduced activity for system A transporters in small-for-gestational-age pregnancies, we found no difference in steady-state concentrations of the mRNA, of the system A transporters among preeclamptic, SGA, and normal control pregnancies. These results do not exclude differences in actual protein levels or activity of the amino acid transporters, which warrant further study.

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 ± 9.7 months postpartum. The homeostasis model of insulin resistance (HOMAIR) [(insulin [microunits per milliliter] × glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 ± 6.7 vs. 30.4 ± 10.2; P < 0.01) and median HOMAIR (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMAIR was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMAIR had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMAIR more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

Objective A single-base polymorphism within the promoter of the gene for tumor necrosis factor α at position -308 relative to the transcriptional start site of the gene is correlated with differences in production of tumor necrosis factor α. There are two allelic forms: TNFA1 and TNFA2. The TNFA2 allele is associated with increased production of tumor necrosis factor α. The purpose of this study is to assess the relationship between carriage of the TNFA2 allele and clinical chorioamnionitis. Methods In this retrospective cohort study, previously banked deoxyribonucleic acid from 149 women who had spontaneous labor from 37 to 42 weeks’ gestation was used. Polymerase chain reaction was used for polymorphism assay. Demographic and clinical information was obtained from the medical record. Clinical chorioamnionitis was defined as at least one temperature elevation above 38C combined with at least two of the following signs: maternal or fetal tachycardia, uterine tenderness greater than expected, foul-smelling vaginal discharge, and white blood cell count more than 18,000. Results Chorioamnionitis was present in 18 women (12.1%). Among women who did not carry TNFA2, the chorioamnionitis rate was 7.4%. Among women who carried TNFA2, the chorioamnionitis rate was 24.4%. The relative risk for chorioamnionitis with carriage of TNFA2 was 3.3 (95% confidence interval 1.3, 7.1). This increased risk was not altered after adjustment for race, type of rupture of membranes, intrauterine pressure catheter use, smoking, and prolonged rupture of membranes. Conclusion Carriage of the TNFA2 allele is associated with a more than three-fold increased risk of clinical chorioamnionitis, even when accounting for important clinical and microbiologic risk factors.

The pathophysiology of pre-eclampsia is contested, but one hypothesis indicates that it is a heterogeneous condition in which only a subset of affected women bear small-for-gestational age (SGA) babies. In intrauterine growth-restricted (IUGR) infants, placental transport of amino acids is diminished and the resulting decrease in cord-blood amino acid concentrations is thought to contribute to their stunted growth. In contrast, the metabolic syndrome (dyslipidaemia, hyperinsulinaemia, hyperglycaemia, hypertension and obesity) which is associated with high amino acid concentrations is more prevalent in women with pre-eclampsia. The focus of this study was to compare maternal and fetal serum amino acid concentrations during normal pregnancy and pre-eclampsia and to evaluate the associations between the amino acid concentrations and fetal growth. The results indicate that maternal and cord-blood amino acid concentrations were significantly higher in women with pre-eclampsia compared with normal pregnant women and the concentrations were inversely associated with measures of infant growth. Maternal and cord-blood amino acid concentrations were also significantly higher in pre-eclamptic mothers with SGA infants compared with pre-eclamptic mothers whose babies were not SGA. These data indicate that, in contrast to IUGR, pre-eclampsia is associated with enhanced placental amino acid transport or reduced fetal amino acid utilization. Furthermore, the data are consistent with the hypothesis that pre-eclampsia is a heterogeneous disease associated with the metabolic syndrome.

Pre-eclamptic (PE) placentae overexpress hypoxia inducible transcription factors-1alpha and -2alpha proteins (Biol. Repro. 64: 499-506, 2001; Ibid 1019-1020). Possible explanations include (a) impaired oxygen-dependent reduction, and/or (b) enhanced sensitivity to reduced oxygen. After 18 h equilibration under 21 per cent O(2) atmosphere, we subjected villous explants prepared from placentae of normal pregnant (NP) and pre-eclamptic (PE) women (n=8 each) to 4h of hypoxia (2 per cent oxygen), and then studied the disappearance of HIF-1alpha and -2alpha proteins during subsequent oxygenation over 90 min (21 per cent oxygen). The disappearance of these HIF proteins as assessed by Western analysis was significantly impaired in the pre-eclamptic tissues. Even after 18h equilibration under a 21 per cent O(2) atmosphere, and then a further 4h at 21 per cent O(2), HIF-1alpha and -2alpha protein expression remained increased in villous explants from PE women (both P< 0.04 vs NP). To address whether chronic hypoxia per se (which is believed to exist in the pre-eclamptic placenta) might contribute to these findings, we subjected villous explants from normal placentae (n=6) to 18 h preincubation under 2 per cent or 21 per cent oxygen prior to subsequent incubation for 4h at 2 per cent oxygen and then 90 min at 21 per cent oxygen. The time course of disappearance of HIF proteins during oxygenation was similar irrespective of the 2 per cent or 21 per cent preconditioning. To evaluate oxygen sensitivity, we exposed villous explants from NP and PE women (n=6 each) to different oxygen atmospheres for 4h and measured HIF protein induction. Although the data showed a significant inverse relationship between HIF expression and oxygen concentration, there was no significant difference between the slopes of this relationship for the two groups of women. We conclude that villous explants from PE placentae fail to adequately downregulate HIF protein expression upon oxygenation. This abnormality may contribute to their overexpression in vivo.

Transcription factors orchestrate the development of extraembryonic tissues. Because placental hypoxia likely plays an important role in both normal and abnormal placentation, we have been investigating the hypoxia-inducible transcription factors (HIFs) in the human placenta. In this report, we focus on the placentas from women with preeclampsia. Because the placenta is a large, heterogeneous organ, we employed a systematic and unbiased approach to placental sampling, and our results are based on the analyses of eight biopsy sites per placenta. We observed no significant differences in HIF-1a or -2a mRNA expression between normal term and preeclamptic placentas. Nor was HIF protein expression significantly different, with the notable exception of HIF-2a, which, on average, was increased by 1.7-fold in the preeclamptic placentas (P , 0.03 vs. normal term placentas). Considering all 48 paired placental biopsy sites (eight sites each for six normal term and six preeclamptic placentas), HIF-2a protein levels in the preeclamptic placentas exceeded those in the normal term placentas in 39, or 81%, of the paired sites (P , 0.0013). The HIF-2a immunoreactivity was mainly located in the nuclei of the syncytiotrophoblast and fetoplacental vascular endothelium in the preeclamptic villous placenta. To control for the earlier gestational age of the preeclamptic placentas, an additional group of placentas from preterm deliveries without preeclampsia were also evaluated. The HIF protein expression was comparable in these preterm specimens and the normal term placentas. We conclude that protein expression of HIF-2a, but not of HIF-1a or -1b, is selectively increased in the preeclamptic placenta. The molecular mechanism(s) of this abnormality as well as the genes affected downstream are currently under investigation. To our knowledge, this is the first report of abnormal HIF-2a expression in human disease other than cancer. developmental biology, gene regulation, placenta, syncytiotrophoblast, trophoblast

ObjectiveTo examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.DesignLongitudinal study.SettingInformation about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.SubjectsInfants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.ResultsDaily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.ConclusionsMost of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.

More than 27% of pregnant women fall. Approximately 40% of falls occur during staircase locomotion. The purpose of this study was to examine ground reaction forces in pregnant fallers, pregnant non-fallers, and non-pregnant controls to determine if pregnant fallers display alterations to ground reaction forces that increase their risk of falling on stairs.Fifteen pregnant fallers and 14 pregnant non-fallers participated during their second and third trimesters. Forty non-pregnant women served as controls. Subjects ascended and descended a four-step staircase. A force plate in the second stair collected ground reaction forces. Ascent and descent velocities were assessed. In the statistics, group (pregnant faller, pregnant non-faller, control) and subject were independent variables. Stance time and ascent/descent velocity were analyzed with an ANOVA. Mediolateral center of pressure excursion was analyzed with an analysis of covariance. Ground reaction forces were categorized into anterioposterior, mediolateral, and vertical forces and normalized to the subject's bodyweight. A multivariate analysis of covariance was used to compare between groups and subjects for each force category, with velocity as the covariate (α = 0.05).Pregnant fallers had an increased anterioposterior braking impulse (P0.01), medial impulse (P = 0.02), and minimum between vertical peaks (P =0.01) during ascent. During descent, pregnant fallers demonstrated a smaller anterioposterior propulsive peak and propulsive impulse (P = 0.03) and a greater minimum between vertical peaks (P0.01).These alterations are likely related to a strategy used by pregnant fallers to increase stability during staircase locomotion.

The purpose of this study was to determine in vivo the dose response relationship between β-adrenergic receptor (BAR) agonist concentration and various elements of the BAR cascade: receptor density, hormone-stimulable adenylyl cyclase activity, and contraction inhibition.A previously described, chronically-catheterized ovine model was used. Ritodrine was infused continuously over 24 h in 22 mixed-breed sheep. Each animal received a single, constant infusion rate. Myometrial biopsies were obtained before and after the drug infusions. BAR density was determined using tritiated dihydroalprenolol. Adenylyl cyclase activity was determined using the Oilman competitive protein-binding assay. Intermittent oxytocin boluses were given into the maternal aorta and contractile response was determined.Infusion rates of 0.06–4.0 μg/kg/min yielded steady-state ritodrine serum concentrations of 5–168 ng/ml. No significant correlation was found between the ritodrine concentration and the magnitude of decrease in BAR densit...

In this article, we will review the pharmacokinetics and pharmacology of the most frequently used labor inhibiting agents with a view toward optimizing efficacy and minimizing adverse side effects.

Pregnant women are at an increased risk of experiencing a fall. Numerous anatomical, physiological, and hormonal alterations occur during pregnancy, but the influence of these factors on dynamic postural stability has not been explored. The purpose of this study was to examine dynamic postural stability in pregnant women during their second and third trimesters as well as in a group of non-pregnant control women.Eighty-one women (41 pregnant, 40 controls) participated stood on a force plate that translated anteroposteriorly at small, medium, and large magnitudes. Reaction time and center of pressure (COP) movement during the translations were analyzed. Trimester, perturbation direction, and perturbation magnitude were the independent variables in a mixed-model analysis of variance on each of the following dependent variables: reaction time, initial sway, total sway, and sway velocity.Reaction time to the perturbation was not significantly different between the groups. Initial sway, total sway, and sway velocity were significantly less during the third trimester than during the second trimester and when compared to the non-pregnant controls (P0.05). No differences were found in any of the measures between the pregnant women in their second trimesters and the control group.Alterations in sway responses to perturbations are seen in the third trimester in healthy women with uncomplicated pregnancies. Further study is needed to examine the biomechanical and physiological reasons behind this altered dynamic postural stability.

Objective We hypothesized that body composition would be similar among neonates of women with gestational diabetes (GDM) treated with glyburide or insulin. Study Design Women with GDM requiring medical therapy were randomized to insulin or glyburide. The primary outcome was percent neonatal fat mass measured by total body electrical conductivity. Secondary outcomes included anthropometrics, glycemic control, and biomarkers. Statistical analysis included Student t test, χ 2 , and regression modeling. Results Eighty-two neonates underwent postnatal measurements. Baseline factors were not different by group. Neonatal percent fat mass did not differ between treatment groups (11.2 ± 4.2 vs 12.8 ± 5.7). Fat mass, body mass index, ponderal index, skinfold sum, and arm fat area were not different when analyzed by intent to treat or actual treatment group. Cord concentrations of biomarkers were also similar. Conclusion There was no difference in neonatal adiposity in infants of women treated for GDM with glyburide or insulin.

Summary Objective Adipocytokines are important regulators of insulin resistance. The aim of this study was to compare maternal adipocytokines in early pregnancy among women diagnosed with and without gestational diabetes (GDM) months later. Design A nested case-control study. Patients Adiponectin, resistin and interleukin-6 (IL-6) were measured in 59 nulliparous women (30 women with GDM and 29 controls) in plasma obtained in early pregnancy. Patients underwent routine testing for GDM in late pregnancy. Measurements Adiponectin was measured using radioimmunoassay. Resistin and IL-6 were measured by ELISA. Statistical analysis included Student's t-test, logistic regression and Pearson's correlation. Results Groups were not different by baseline descriptors or obstetric outcomes. Mean gestational age at sampling was 9·3 ± 2·6 weeks. Adiponectin was lower (P

Objective We investigated changes in serum uric acid across pregnancy in women with gestational hyperuricemia at delivery, with and without preeclampsia, compared with normal pregnant and women with preeclampsia without gestational hyperuricemia. Study design This was a nested case-control study of 116 controls, 27 women with preeclampsia with predelivery hyperuricemia, 37 women with preeclampsia without predelivery hyperuricemia, and 35 women with gestational hypertension with hyperuricemia at delivery but without proteinuria. Serum uric acid and creatinine was measured across pregnancy. Results Women with predelivery hyperuricemia, with and without preeclampsia, had increased uric acid concentrations across pregnancy compared with controls, after 25 weeks' gestation compared with women with preeclampsia without predelivery hyperuricemia. Adjusting for differences in glomerular filtration by serum creatinine accounted for part but not all of the increase in serum uric acid among women with preeclampsia and predelivery hyperuricemia. Conclusions Among women with hyperuricemia at delivery, elevations in uric acid occur early. Multiple mechanisms may contribute to increased uric acid including changes in renal function.

S -nitrosoalbumin (SNO-Alb) is a major reservoir of releasable nitric oxide (NO) in plasma. In preeclampsia, a pregnancy-specific disorder associated with endothelial dysfunction, we previously found significant elevations in plasma SNO-Alb concentrations and decreased plasma ascorbate (Asc) levels. This increased SNO-Alb may result from low-plasma Asc if Asc, along with transition metals (eg, copper [Cu]) are necessary for release of NO from S -nitrosothiols. We propose that vasodilator effects of SNO-Alb, mediated by release of NO, are fully realized only when Asc/Cu availability is sufficient. Relaxation responses to SNO-Alb or the control reduced human serum albumin (SH-Alb), and responses to pooled plasma from normal or preeclamptic pregnancies were examined in isolated mouse arteries. Arteries preconstricted with phenylephrine were exposed to SNO-Alb or SH-Alb at physiologically relevant concentrations. When free Cu was added in excess (10 μmol/L), NO release was not dependent on Asc. However, when Cu was added at lower (physiological) levels, NO release was dependent on Asc. The addition of Asc and Cu to SNO-Alb stimulated vasodilatory responses in isolated arteries >90%, whereas no change in the SH-Alb (5%) response was observed. Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1±4.7%, whereas normal pregnancy plasma caused 11.9±4.2% relaxation ( P =0.007). These data indicate that SNO-Alb alone or in plasma can act as a potent vasodilator, and that sufficient Asc/Cu promotes this action. We suggest that the higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a deficiency in Asc/Cu-mediated release of NO from SNO-Alb.

The hypoxia inducible transcription factors, HIF-1alpha and -2alpha proteins, are overexpressed in placentae from women with preeclampsia (Biol Reprod 2001;64:499-506; Biol Reprod 2001;64:1019-1020). Normally, these proteins are regulated in an oxygen-dependent manner being rapidly degraded by the ubiquitin-mediated proteasomal pathway. Recent studies have shown that the tumor suppressor protein, von Hippel Lindau (VHL), targets HIF for ubiquitinylation under nonhypoxic conditions. The objectives of the present work were: (1) to investigate VHL protein expression in normal pregnant (NP), preeclamptic (PE), and preterm (without PE) placentae, (2) to test whether VHL protein is hypoxia inducible in term and first trimester placental villous explants, and (3) to analyze the ontogeny of VHL protein expression in the human placenta. To begin evaluating the potential contribution of VHL to HIF overexpression in preeclamptic placentae, we analyzed the levels of the VHL protein in both normal and preeclamptic placentae (n=7 each). We hypothesized a deficiency of VHL protein in preeclamptic placentae. Eight biopsy sites were tested in each placenta and protein extracts were made. Western analysis was performed using VHL specific antibodies. Human renal adenocarcinoma (ACHN) cell extracts and extracts from COS-7 cells transfected with a VHL expression vector were used as positive controls. In a total of 112 biopsy sites that were analyzed (56 each for normal and preeclamptic placentae), the composite densitometry ratios (PE/NP) for the long (28 kDa) and short (19 kDa) forms of VHL were 1.09+/-0.2 and 1.16+/-0.11, respectively (both p=NS vs 1.0). A ratio of 1.0 indicates equal expression by preeclamptic and normal placentae. The same placentae exhibited composite densitometry (PE/NP) ratios of 1.97+/-0.23 and 1.68+/-0.20 for HIF-1alpha and -2alpha proteins, respectively (both p

Black women have an increased risk of preeclampsia compared with white women. Plasma homocysteine is increased in preeclampsia. Homocysteine concentrations are affected by nutritional deficiencies, particularly decreased folic acid and B12, leading to increased homocysteine. Previous studies have reported racial differences in nutritional intake including folic acid. Therefore, we investigated whether there were racial differences in plasma homocysteine, folic acid, and vitamin B12 among women with preeclampsia. We tested for an association between homocysteine and folic acid and B12, and we hypothesized an inverse relationship of homocysteine and folic acid in preeclampsia, more so in black women in whom preeclampsia developed. Black women with preeclampsia (n=26) had elevated homocysteine concentrations (8.7±1.4 μmol/L) compared with black women with normal pregnancy (n=52, 7.6±0.5 μmol/L), white women with preeclampsia (n=34, 7.5±0.6 μmol/L), and white women with normal pregnancy (n=48, 5.5±0.3 μmol/L). Folic acid concentrations were lower in black women (14.1±0.8 ng/mL) compared with white women (18.5±0.9 ng/mL, P r =−0.23, P =0.01). These racial differences may have implications for the higher rates of preeclampsia in this group and may have long-term implications for future cardiovascular risk. Racial differences in diet, adherence to folic acid supplementation, or interactions of nutritional and maternal factors warrant further study by race and pregnancy status.

Placentas from women with preeclampsia overexpress the hypoxia-inducible transcription factor proteins, HIF-1alpha and -2alpha (Rajakumar 2001, Biol Reprod 64; p499-506 and p1019-1020). As a first step in evaluating whether HIF-alpha overexpressed in preeclamptic placentae is capable of transactivation, we tested its ability to bind to the DNA hypoxia response element (HRE). Six pairs of normal and preeclamptic placentae obtained by cesarean section were investigated. Three biopsy sites per placenta were analyzed. We first confirmed HIF-1alpha protein overexpression in the preeclamptic placentae using Western analysis. The ratios of the arbitrary densitometry units for HIF-1alpha protein from the preeclamptic and normal placentae (PE/NP) in the three biopsy sites were: 1.9 +/- 0.3, 1.7 +/- 0.2 and 1.8 +/- 0.2, each p0.05 vs 1.0. (A ratio of1.0 indicates that HIF-1alpha protein expression in placentas of women with PE exceeds that in placentas of NP women.) Conventional methods for extracting nuclear proteins and subsequent analysis by electrophoretic mobility shift assay were not suited for the frozen, archived samples (data not shown). Therefore, we employed DNA affinity chromatography using a biotinylated oligonucleotide representing the HRE of the erythropoietin gene coupled to streptavidin-coated Dynabeads. The HRE-bound proteins were then characterized by Western blot analysis. The PE/NP ratios of HRE-bound HIF-1alpha in the three biopsy sites from the six pairs of normal and preeclamptic placentae were 1.7 +/- 0.2, 2.1 +/- 0.4 and 2.4 +/- 0.5, each p0.05 vs 1.0. Having established DNA-binding potential at least in vitro, we subsequently analyzed three proteins that have been shown to be regulated by HIF-alpha as downstream, molecular markers of HIF-1alpha activity in vivo. VEGF receptor Flt-1 and Flk-1 play key roles in angiogenesis. Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis. All three genes contain functional HRE in their promoter sequences. Total proteins were extracted from the same biopsy samples that were used for total and HRE-bound HIF-1alpha. Using specific antibodies we performed Western analysis and the levels of these three proteins were quantitated. The Flt-1 and tyrosine hydroxylase proteins were significantly higher, and Flk-1 significantly lower in placentae from preeclamptic compared to normal pregnancies. In summary, HIF-1alpha protein overexpressed in preeclamptic placentae is capable of binding to its DNA recognition sequence in vitro, and modulates gene expression in vivo.

Risks of some cancers in adults have been associated with several pregnancy factors, including greater maternal age and birth weight. For hormone-related cancers, these effects are hypothesized to be mediated through higher in utero estrogen concentrations. In addition, racial differences in pregnancy hormone levels have been suggested as being responsible for differences in testicular and prostate cancer risk by race. However, data on hormonal levels related to these characteristics of pregnancy are sparse, particularly those from studies of the fetal circulation.Estrogen and androgen concentrations were measured in maternal and umbilical cord sera from 86 normal, singleton pregnancies.Birth size measures (weight, length and head circumference) were positively correlated with maternal estriol (r = 0.25-0.36) and with cord DHEAS concentrations (r = 0.24-0.41), but not with estrogens in cord sera. Maternal age was inversely correlated with maternal DHEAS, androstenedione and testosterone concentrations (r = -0.30, -0.25 and -0.30, respectively), but uncorrelated with estrogens in either the maternal or cord circulation. Black mothers had higher androstenedione and testosterone concentrations than white mothers, however, there were no racial differences in any of the androgens in cord sera. Cord testosterone concentrations were higher in mothers of male fetuses, while both maternal and cord concentrations of estriol were lower in these pregnancies.These data demonstrate associations between hormone concentrations and pregnancy factors associated with offspring's cancer risk, however, the hormones involved and their patterns of association differ by whether the maternal or fetal circulation was sampled. Hormone concentrations in the fetal circulation in this study are not consistent with the hypothesis that greater estrogen concentrations in high birth weight babies mediate the positive association with breast cancer risk observed in epidemiologic studies, or with the hypothesis that higher testosterone exposure in the in utero environment of black males explains their higher subsequent prostate cancer risk.

Study Objectives: To study labor outcomes in parturients receiving oxytocin for augmentation or induction of labor, in the presence of labor epidural analgesia. Design: Retrospective study of data from a continuous quality improvement database. Setting: Tertiary-care hospital with more than 8000 deliveries per annum. Measurements and Main Results: Of the 1671 healthy nulliparous women with singleton pregnancies and who requested labor epidural analgesia at our institution, 675 patients received oxytocin during elective induction of labor, whereas 996 patients received oxytocin for augmentation of spontaneous labor. Measured variables were cervical dilatation at time of epidural analgesia request, epidural insertion to 10-cm time, duration of stage 2 of labor, normal spontaneous vaginal delivery rate, cesarean section rate, operative vaginal delivery rate, and baby weight. Women admitted for induction of labor requested epidural analgesia sooner than those who had their labor augmented (p (p = 0.008). Conclusion: Patients who have their labor induced request analgesia sooner and are at a higher risk of cesarean section than are patients who go into labor spontaneously. Any study that purports to assess the effects of epidural analgesia in labor should distinguish between induced and augmented/spontaneous labor.