Cardiac morphology in neonates with fetal growth restriction.

OBJECTIVE: Assess effects of fetal growth restriction (FGR) on cardiac modelling in premature and term neonates. STUDY DESIGN: Prospective echocardiographic study of a cohort of FGR neonates (n = 21) and controls (n = 41) with normal prenatal growth and circulation. RESULTS: Unadjusted for gestational age, birth weight, sex, and twin/singleton, Late-FGR neonates had smaller hearts than controls, with globular left ventricles and symmetrical right ventricles. Adjusted estimates showed smaller left ventricles and similarly sized right ventricles, with symmetrical left and right ventricles. Early-FGR (compared with Late-FGR) had smaller hearts and globular left ventricles in unadjusted estimates, but after adjustment, sizes and shapes were similar. CONCLUSION: FGR had significant impact on cardiac modelling, seen in both statistical models unadjusted and adjusted for gestational age, birth weight, sex, and twin/singleton. The adjustments, however, refined the results and revealed more specific effects of FGR, thus underscoring the importance of statistical adjustments in such studies.

Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis.

Background: : Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.

Plasma calprotectin as inflammation marker in pregnancies complicated by diabetes mellitus and superimposed preeclampsia.

OBJECTIVE: We hypothesized that pregnancies complicated by diabetes mellitus with or without preeclampsia show an elevated systemic inflammatory response evaluated by the inflammation markers calprotectin and high-sensitivity C-reactive protein (hsCRP). STUDY DESIGN: Third trimester EDTA plasma and serum from 138 women with diabetes mellitus (type 1, n=53; type 2, n=11; gestational diabetes mellitus (GDM), n=63; diabetes mellitus with preeclampsia, n=11) were analyzed for calprotectin and hsCRP and compared to previously published results from 37 healthy and 27 preeclamptic pregnancies. RESULTS: Median plasma calprotectin concentration was intermediate in women with GDM as compared to healthy and preeclamptic pregnancies (729 vs 552 and 1081µg/L, P=.006 and P=.001, respectively). In diabetic pregnancies with preeclampsia, median plasma calprotectin concentration was elevated as compared to controls, but not different from women with preeclampsia alone (969 vs 552 and 1081µg/L, P=.01 and P=.1, respectively). hsCRP was only elevated in type 2 diabetic pregnancies as compared to healthy pregnancies (6.6 vs 3.8mg/L, P=.02). CONCLUSION: Elevated plasma calprotectin concentrations in GDM may reflect an accentuated inflammatory process, possibly contributing to the augmented preeclampsia risk. Increased plasma calprotectin in diabetic pregnancies with preeclampsia may originate from the excess systemic inflammatory response associated with preeclampsia.

Asymmetric dimethylarginine in the maternal and fetal circulation in preeclampsia.

Preeclampsia is a leading cause of intrauterine growth restriction and preterm birth. Endothelial dysfunction is the common final pathway leading to clinical signs of preeclampsia including hypertension and proteinuria. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS and induces endothelial dysfunction by reversibly inhibiting NO production from l-arginine. The purpose of this study was to investigate maternal and fetal concentrations of ADMA, l-arginine, and symmetric dimethylarginine (SDMA). Women with preeclampsia (n = 47) and controls (n = 51) who gave birth by cesarean section were included in the study. We analyzed the maternal plasma and umbilical vein and artery plasma. We found that not only maternal concentrations of ADMA and SDMA but also l-arginine were significantly higher in women with preeclampsia than in controls. In fetal samples, only SDMA concentrations were higher in the preeclampsia group than in controls. The median ADMA concentration was three times higher in the fetal circulation than in the maternal circulation, but there was no difference between the preeclampsia group and the control group, and the veno-arterious gradient indicated that the placenta was the source of ADMA.

Maternal, gestational and neonatal characteristics and maternal angiogenic factors in normotensive pregnancies.

OBJECTIVE: Alterations in maternal circulating angiogenic factors are proposed to result in hypertension and proteinuria and development of preeclampsia. The aim of this study was to explore whether preeclampsia risk factors are associated with maternal angiogenic profile in normotensive pregnancies. STUDY DESIGN: Associations of pregnancy characteristics and maternal serum concentrations at delivery of proangiogenic placental growth factor (PlGF), antiangiogenic soluble fms-like tyrosine kinase receptor (sFlt1) and soluble endoglin (sEng), as well as the antiangiogenic ratios sFlt1/PlGF and (sFlt1+sEng)/PlGF were analyzed in 43 normotensive and 44 preeclamptic pregnancies. RESULTS: In normotensive pregnancies, increasing maternal age was associated with a more antiangiogenic profile, including lower PlGF concentrations and a higher (sFlt1+sEng)/PlGF ratio (P<0.05). In preeclampsia, shorter length of gestation and lower birth weight percentile were associated with a more antiangiogenic profile. CONCLUSION: A greater antiangiogenic profile with older maternal age may suggest a biological mechanism which mediates this preeclampsia risk factor. In preeclampsia, the antiangiogenic state was more pronounced with clinical characteristics indicative of greater disease severity.

Advanced glycation end products in pregnancies complicated with diabetes mellitus or preeclampsia.

OBJECTIVE: Preeclampsia (PE) and diabetes mellitus (DM) are associated with oxidative stress. DM is complicated with formation of advanced glycation end products (AGEs), which are associated with oxidative stress. We hypothesized that elevated serum AGE would be found in pregnancies complicated by PE or DM. METHODS: Circulating AGEs, 8-isoprostane, vitamin E, and antioxidant capacity were analyzed from study patients. RESULTS: Serum AGE was elevated both in patients with type 1 DM and gestational DM, but not in PE, compared with controls. 8-isoprostane was elevated in patients with type 1 DM and PE compared with controls. CONCLUSION: AGEs and 8-isoprostane are not elevated in parallel in pregnancies complicated with PE or DM, suggesting biological heterogeneity.

Blood pressure augmentation and maternal circulating concentrations of angiogenic factors at delivery in preeclamptic and uncomplicated pregnancies.

OBJECTIVE: The objective of the study was to determine whether blood pressure increases are associated with maternal angiogenic factors in uncomplicated and preeclamptic pregnancies. STUDY DESIGN: Associations of blood pressure increases from mid- to late pregnancy with maternal serum concentrations of soluble fms-like tyrosine kinase receptor (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) at delivery were analyzed in 43 uncomplicated and 44 preeclamptic pregnancies. RESULTS: In uncomplicated pregnancies, increases in diastolic and mean arterial pressure were inversely associated with PlGF at delivery and positively associated with sEng and sFlt1/PlGF ratio. There were no significant associations between blood pressure increases and angiogenic factor concentrations in preeclampsia. CONCLUSION: These data suggest that angiogenic factors are involved in blood pressure modulation in normotensive pregnancy and are consistent with the hypothesis that angiogenic balance plays a role in maternal breast cancer risk reduction associated with mid- to late blood pressure increases in uncomplicated pregnancies.

Circulating concentrations of soluble endoglin (CD105) in fetal and maternal serum and in amniotic fluid in preeclampsia.

OBJECTIVE: We explored whether concentrations of soluble endoglin in fetal serum and amniotic fluid and in maternal serum were elevated in preeclampsia. STUDY DESIGN: Umbilical vein serum, amniotic fluid, and maternal serum from 42 preeclamptic and 43 uncomplicated pregnancies that were delivered by cesarean section were analyzed by enzyme-linked immunosorbent assay for soluble endoglin. RESULTS: Median maternal serum and amniotic fluid soluble endoglin concentrations were elevated in preeclampsia, compared with control pregnancies (66.9 ng/mL vs 15.1 ng/mL; P < .001, and 1.9 ng/mL vs 0.6 ng/mL; P < .001). Low concentrations of soluble endoglin were found in fetal circulation, which did not differ between preeclampsia and control pregnancies (5.0 ng/mL vs 4.7 ng/mL; P = .2). Maternal serum soluble endoglin levels correlated with circulating soluble fms-like tyrosine kinase 1 concentrations. CONCLUSION: We confirmed elevated soluble endoglin in maternal circulation in preeclampsia, which correlated with soluble fms-like tyrosine kinase 1 concentrations and soluble fms-like tyrosine kinase 1/placental growth factor ratio. The fetus appears not to contribute to elevated circulating maternal soluble endoglin concentrations in preeclampsia.

Homocysteine, cysteine, and related metabolites in maternal and fetal plasma in preeclampsia.

Homocysteine is associated with endothelial dysfunction and cardiovascular disease, and elevated concentrations of homocysteine have been found in preeclampsia. The purpose of this study was to investigate maternal and fetal concentrations of total homocysteine and related metabolites (including cysteine, choline, and betaine), and possible associations with infant birth weight. Women with preeclampsia (n=47) and controls (n=51), who underwent cesarean section, were included. Maternal plasma, umbilical vein, and artery plasma were analyzed. Median concentrations of homocysteine, cysteine, choline, and betaine were significantly higher in women with preeclampsia than controls, both in maternal and fetal plasma. There were no differences in folate and vitamin B12 concentrations between the groups, neither for maternal nor fetal samples. Maternal homocysteine concentration was a negative predictor for birth weight only in the preeclampsia group. Elevated homocysteine and cysteine concentration in maternal circulation in preeclampsia is reflected in the fetal circulation. The clinical significance of elevated homocysteine and cysteine concentrations in maternal and fetal compartments in preeclampsia remain to be explored, both regarding fetal growth and development of disease later in life.

Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.

The renin-angiotensin system (RAS) participates in preeclampsia; however, the relative contributions from the circulating RAS and the tissue-based, uteroplacental RAS are unknown. We hypothesized that the tissue-based uteroplacental RAS is dysregulated in preeclampsia. We performed microarray and gene expression studies and confirmed the findings on the protein level by immunohistochemistry in ureteroplacental units from 10 preeclamptic women and 10 women with uneventful pregnancies. All of the women were delivered by cesarean section. We also analyzed plasma renin activity and circulating agonistic angiotensin II type 1 (AT1) receptor autoantibodies. In preeclampsia, we found that the angiotensin II AT1 receptor gene was 5-fold upregulated in decidua (maternal origin). We also found AT1 autoantibodies in preeclamptic women and in their offspring by neonatal cardiomyocyte bioassay compared with women with normal pregnancies and their infants (mother: 17.5+/-2.2 versus 0.05+/-0.4; fetus: 14.5+/-1.8 versus 0.5+/-0.5 Deltabpm). Gene expressions for renin (35.0-fold), angiotensin-converting enzyme (2.9-fold), and angiotensinogen (8.9-fold) were higher in decidua than placenta (fetal origin) in both control and preeclamptic women, whereas the AT1 receptor was expressed 10-fold higher in placenta than in decidua in both groups. Our findings elucidate the ureteroplacental unit RAS in preeclamptic and normal pregnancies. We found that, in preeclampsia, the AT1 receptor expression is particularly high in decidua, combined with pregnancy-specific tissue RAS involving decidual angiotensin II production and AT1 autoantibodies. We also showed that AT1 autoantibodies cross the ureteroplacental barrier. These components could participate in the pathophysiology of preeclampsia.

Oxidative stress and antioxidant status in fetal circulation in preeclampsia.

Preeclampsia is associated with oxidative stress in maternal circulation. The purpose of this study was to explore oxidative stress and antioxidants in the fetal circulation in preeclampsia. Women with preeclampsia (n = 19) or uncomplicated pregnancies (n = 33) delivered by cesarean section were included. Blood was sampled separately from the umbilical vein and artery. 8-Iso-prostaglandin F(2alpha) (8-isoprostane), a stable product of lipid peroxidation, is a reliable marker of oxidative stress. Concentration of total 8-isoprostane in cord plasma was analyzed by gas chromatography-mass spectrometry. Antioxidant status was evaluated measuring ferric reducing ability of plasma and vitamin E. There was no difference between preeclampsia and control groups regarding median plasma concentration of 8-isoprostane in umbilical vein (955 versus 780 pg/mL, p = 0.41) or in umbilical artery (233 versus 276 pg/mL, p = 0.65). Concentration of 8-isoprostane was much higher in plasma from the umbilical vein than artery, suggesting placenta as the source of 8-isoprostane. Median ferric reducing ability of plasma concentration was higher in preeclampsia than in controls, both in the umbilical vein and artery. Median vitamin E concentration in the umbilical vein was higher in preeclampsia, but no difference was found in the umbilical artery. In conclusion, no evidence of increased oxidative stress, evaluated by 8-isoprostane concentration, was found in fetal circulation in preeclampsia.

Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line.

Transplacental transfer of maternal fatty acids is critical for fetal growth and development. In the placenta, a preferential uptake of fatty acids toward long-chain polyunsaturated fatty acids (LCPUFAs) has been demonstrated. Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that has been ascribed a role in cellular fatty acid uptake and storage. However, its role in placenta is not known. We demonstrate that ADRP mRNA and protein are regulated by fatty acids in a human placental choriocarcinoma cell line (BeWo) and in primary human trophoblasts. LCPUFAs of the n-3 and n-6 series [arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3), and eicosapentaenoic acid (20:5n-3)] were more efficient than shorter fatty acids at stimulating ADRP mRNA expression. The fatty acid-mediated increase in ADRP mRNA expression was not related to the differentiation state of the cells. Synthetic peroxisome proliferator-activated receptor and retinoic X receptor agonists increased ADRP mRNA level but had no effect on ADRP protein level in undifferentiated BeWo cells. Furthermore, we show that incubation of BeWo cells with LCPUFAs, but not synthetic agonists, increased the cellular content of radiolabeled oleic acid, coinciding with the increase in ADRP mRNA and protein level. These studies provide new information on the regulation of ADRP in placental trophoblasts and suggest that LCPUFA-dependent regulation of ADRP could be involved in the metabolism of lipids in the placenta.

Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression.

Adipokines are predominantly secretory protein hormones from adipose tissue but may also originate in placenta and other organs. Cross-sectionally, we monitored maternal plasma concentration of adiponectin, resistin, and leptin and their mRNA expression in abdominal subcutaneous adipose tissue and placenta from preeclamptic (PE; n = 15) and healthy pregnant (HP; n = 23) women undergoing caesarean section. The study groups were similar in age and BMI, whereas HOMA-IR tended to be higher in the PE group. In fasting plasma samples, the PE group had higher concentrations of adiponectin (18.3 +/- 2.2 vs. 12.2 +/- 1.1 microg/ml, P = 0.011), resistin (5.68 +/- 0.41 vs. 4.65 +/- 0.32 ng/ml, P = 0.028), and leptin (34.4 +/- 3.2 vs. 22.7 +/- 2.1 ng/ml, P = 0.003) compared with the HP group. Adiponectin and leptin concentrations were still different between PE and HP after controlling for BMI and HOMA-IR, whereas resistin concentrations differed only after controlling for BMI but not HOMA-IR. We found similar mean mRNA levels of adiponectin, resistin, and leptin in abdominal subcutaneous adipose tissue in PE and HP women. When data were pooled from PE and HP women, resistin mRNA levels in adipose tissue also correlated with HOMA-IR (r = 0.470, P = 0.012) after controlling for BMI and pregnancy duration. Resistin mRNA levels in placenta were not significantly different between PE and HP, whereas leptin mRNA levels were higher in PE placenta compared with HP. Thus increased plasma concentrations of adiponectin and resistin in preeclampsia may not relate to altered expression levels in adipose tissue and placenta, whereas both plasma and placenta mRNA levels of leptin are increased in preeclampsia.

Serious foetal growth restriction is associated with reduced proportions of natural killer cells in decidua basalis.

Extravillous trophoblasts are major participants in placental development and remodelling of spiral arteries. Trophoblast invasion is regulated by maternal immune cells, and abnormal leucocyte subpopulation composition has been reported in implantation failure. In pre-eclampsia (PE), with or without foetal growth restriction (FGR), superficial trophoblast invasion and insufficient remodelling of spiral arteries are common findings. In the present study, we have compared spiral artery remodelling and leucocyte composition in decidual tissue from 30 cases (PE=8, FGR=5, PE + FGR=17) and 31 controls. Six histological remodelling criteria were established, and each pregnancy obtained a remodelling score. Numbers of natural killer (NK) cells (CD56+), T cells (CD3+) and activated (CD25+ or CD69+) leucocytes were determined and related to total leucocyte (CD45+) numbers in serial sections. Cases demonstrated significantly impaired spiral artery remodelling, inappropriate placental growth and reduced NK cell proportions, as compared to controls (P=0.02, P<0.001 and P=0.01, respectively). Reduced NK cell proportion was primarily found in pregnancies complicated by FGR, with or without PE, and a significant positive correlation was observed between NK cell proportion, trophoblast infiltration and placental growth. Our in vivo observations support the hypothesized association between NK cells, impaired placental development and pathogenesis of PE/FGR.

Augmented oxidative stress as well as antioxidant capacity in maternal circulation in preeclampsia.

OBJECTIVES: Isoprostanes are stable markers of oxidative stress. We wanted to assess maternal circulating levels of total 8-isoprostane and indices of antioxidant capacity in preeclampsia compared to uneventful pregnancies. STUDY DESIGN: Total 8-isoprostane concentrations, FRAP (ferric reducing ability of plasma), Vitamin E and d-ROM (diacron reactive oxygen metabolites) were measured in maternal venous blood samples from preeclamptic (n=21) and uncomplicated (n=38) pregnancies at cesarean section. RESULTS: Median total 8-isoprostane concentration was elevated in preeclampsia compared to uncomplicated pregnancies (354 and 218 pg/mL, P=0.02). Median FRAP level was also elevated in preeclampsia compared to uncomplicated pregnancies, but to a lesser degree than 8-isoprostane. A positive correlation between 8-isoprostane and previously analyzed placenta-derived sFlt1 (soluble fms-like tyrosine kinase 1) levels in the maternal circulation was found in preeclampsia. CONCLUSION: We found a relative more increase for the oxidative stress marker (8-isoprostane) than for the antioxidant capacity (FRAP) in preeclampsia compared to uneventful pregnancies.

Calprotectin, a marker of inflammation, is elevated in the maternal but not in the fetal circulation in preeclampsia.

OBJECTIVE: Preeclampsia is associated with excessive inflammatory response compared with normal pregnancy. Calprotectin is an inflammation marker not previously explored in preeclampsia. STUDY DESIGN: Calprotectin in maternal and fetal plasma and amniotic fluid was investigated at cesarean delivery in normal pregnancies and preeclampsia. C-reactive protein (CRP) and plasminogen activator inhibitor type1 (PAI-1) were also analyzed. RESULTS: Maternal median calprotectin, CRP, and PAI-1 concentrations were elevated in preeclampsia (1081 microg/L, 4.8 mg/L, and 51.0 U/mL) compared with control levels (552 microg/L, 3.8 mg/L, and 36.5 U/mL). In the umbilical vein, there were no differences between preeclampsia and controls regarding calprotectin and CRP levels. Maternal calprotectin concentrations correlate with CRP and PAI-1 values for the total study group, but a statistical significant correlation was not found in the preeclamptic group. CONCLUSION: Calprotectin is elevated in the maternal circulation in preeclamptic pregnancies. We found no evidence of inflammatory response in the fetal circulation in preeclampsia.

Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia.

OBJECTIVE: We hypothesized that umbilical vein serum soluble fms-like tyrosine kinase 1 (sFlt1) concentration was augmented in pre-eclampsia. We also explored a possible association between fetal and maternal concentrations of sFlt1. STUDY DESIGN: At cesarean delivery, maternal serum samples from pre-eclamptic (n=38) and uncomplicated (n=32) pregnancies were obtained, as well as umbilical vein serum and amniotic fluid samples. ELISA for human sFlt1, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were performed. RESULTS: Median sFlt1 concentrations were elevated in pre-eclampsia compared to uncomplicated pregnancy, in umbilical venous serum (246 and 163 pg/mL, P=0.04), in maternal serum (9932 and 3417 pg/mL, P<0.001), as well as in amniotic fluid (51,040 and 33,490 pg/mL, P=0.03). A positive association between the fetal and maternal serum levels of sFlt1 was found in the pre-eclampsia group. Median PlGF concentration in the maternal serum was significantly lower in the pre-eclampsia group compared to the control group (82 pg/mL and 169 pg/mL, P<0.001). CONCLUSIONS: sFlt1 concentration is elevated in the fetal circulation in pre-eclampsia, but at a much lower level than in the maternal circulation. The results of our study do not support a substantial fetal contribution to the elevated circulating maternal sFlt1 protein concentration in pre-eclampsia.

The decidual suction method: a new way of collecting decidual tissue for functional and morphological studies.

BACKGROUND: Studies of extravillous trophoblasts and placental bed spiral arteries are essential for a better understanding of pathological pregnancies such as preeclampsia, intrauterine growth restriction and diabetes mellitus. A major challenge is to obtain representative and sufficient tissue for morphological and functional investigations. Currently, tissue material is mostly harvested by placental bed biopsy (PBB). We describe a new suction method to obtain a larger volume of decidual tissue from the placental bed. METHODS: Tissue was harvested in 51 cesarean sections by vacuum suction of the placental bed. Sections from formalin-fixed, paraffin-embedded tissue were routinely stained with hematoxylin and eosin (H&E), immunostained with a panel of antibodies and morphologically examined for the presence of trophoblasts and spiral arteries. The results were compared with those from archive material from PBBs and placental basal plate sections (BPSs). Short-term adverse events were registered for the study patients. Long-term complications were registered from medical charts of 151 women having undergone the decidual suction method (DSM), with a follow-up of 38-60 months. RESULTS: In 86% (n = 44), one random section from the decidual suction material demonstrated at least one spiral artery. In 37% (n = 19), six or more spiral arteries were present. All sections revealed extravillous trophoblasts. No short- or long-term morbidity was recorded. CONCLUSIONS: The decidual suction method represents an important improvement in the work to obtain sufficient decidual tissue for morphological and functional studies of extravillous trophoblast function and spiral artery adaptation. The method is safe, as no short- or long-term complications were registered.

Adiponectin is reduced in gestational diabetes mellitus in normal weight women.

BACKGROUND: Adiponectin is an adipose tissue-derived protein counteracting insulin resistance and inflammation. We have compared women with gestational diabetes mellitus (GDM; n = 22) and normal pregnancies (controls; n = 29) to evaluate whether adiponectin represents a link between endocrine function of adipose tissue and the development of diabetes during pregnancy. METHODS: The participants were categorized according to their prepregnancy body mass index (BMI) into two classes: BMI < 25 and BMI = 25. Plasma concentrations of adiponectin, leptin and insulin were measured by radioimmunoassay (RIA). Total cholesterol, high density lipoprotein (HDL) cholesterol and triacylglycerol were determined by routine enzymatic methods. Expression of adiponectin/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was determined by real-time reverse transcription polymerase chain reaction (RT-PCR) in subcutaneous adipose tissues obtained by excision at cesarean delivery. RESULTS: Among individuals with GDM and BMI < 25 kg/m2 (n = 8), plasma adiponectin concentration was lower than in the controls (n = 20), 8.1 +/- 1.2 microg/mL vs. 12.2 +/- 1.1 microg/mL; p = 0.04). The mean plasma leptin concentrations did not differ between the GDM and control groups. Plasma concentrations of insulin and C-peptide were significantly higher among GDM than control individuals independent of BMI. For all the women included in the study, we found that plasma adiponectin only correlated negatively with prepregnancy and third-trimester (sampling day) BMI (p = 0.03 vs. p = 0.01). In abdominal subcutaneous adipose tissue of pregnant women, adiponectin mRNA levels were lower in GDM than in control subjects (0.77 +/- 0.18 vs. 1.39 +/- 0.15; p = 0.05). CONCLUSIONS: These results indicate that low plasma adiponectin concentration is associated with GDM. In addition, we found that adiponectin mRNA levels in adipose tissue biopsies from GDM subjects were reduced.