adrenomedullin and Birth-Weight

Reduced maternal plasma levels of the peptide vasodilator adrenomedullin have been associated with adverse pregnancy outcomes. We measured the extent to which genetic polymorphisms in the adrenomedullin signaling pathway are associated with birth weight, glycemic regulation, and preeclampsia risk.. We genotyped 1,353 women in the Pregnancy, Infection, and Nutrition Postpartum Study for 37 ancestry-informative markers and for single-nucleotide polymorphisms in adrenomedullin (ADM), complement factor H variant (CFH), and calcitonin receptor-like receptor (CALCRL). We used linear and logistic regression to model the association between genotype and birth weight, glucose loading test (GLT) results, preeclampsia, and gestational diabetes (GDM). All models were adjusted for pregravid body mass index, maternal age, and probability of Yoruban ancestry. p values of < 0.05 were considered statistically significant.. Among Caucasian women, ADM rs57153895, a proxy for rs11042725, was associated with reduced birth weight z-score. Among African-American women, ADM rs57153895 was associated with increased birth weight z-score. Two CALCRL variants were associated with GDM risk. CFH rs1061170 was associated with higher GLT results and increased preeclampsia risk.. Consistent with studies of plasma adrenomedullin and adverse pregnancy outcomes, we found associations between variants in the adrenomedullin signaling pathway and birth weight, glycemic regulation, and preeclampsia.

Topics: Adolescent; Adrenomedullin; Adult; Birth Weight; Black or African American; Calcitonin Receptor-Like Protein; Complement Factor H; Diabetes, Gestational; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Linear Models; Logistic Models; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Signal Transduction; White People; Young Adult

Adrenomedullin (ADM) is one of the strongest endogenous vasodilating hormones. Its stable by-product midregional-proADM (MR-proADM) is an established indicator of systemic infection and cardiovascular compromise in adult patients.. A prospective cross-sectional study was performed to investigate the perinatal factors affecting MR-proADM plasma concentrations in 328 newborn infants with a gestational age (GA) between 24 and 41 wk.. Blood samples were obtained in 270 infants from umbilical veins (with additional 108 paired samples from umbilical arteries), and at 2-3 d of life in 183 infants. Paired venous and arterial umbilical cord MR-proADM concentrations were closely related (Spearman's rank order correlation coefficient (R(s)) = 0.825, P < 0.001). MR-proADM concentrations at birth and at 2-3 d were inversely related to GA (R(s) = -0.403 and R(s) = -0.541, respectively) and birth weight (BW; R(s) = -0.421 and R(s) = -0.530, respectively; all P < 0.001). On stepwise regression analysis, clinical chorioamnionitis and umbilical arterial blood base excess retained a significant impact on MR-proADM cord venous blood concentrations. At 2-3 d of life, histologic chorioamnionitis and GA at delivery were significantly associated with MR-proADM levels.. As compared with adults, MR-proADM concentrations are elevated in neonates, especially those born very preterm. Immaturity and infection, which both feature low systemic vascular resistance, are related to increased MR-proADM concentrations.

Topics: Adrenomedullin; Birth Weight; Cross-Sectional Studies; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infections; Male; Prospective Studies; Protein Precursors; Regression Analysis

Proadrenomedullin (pro-ADM) for the diagnosis of proven and clinical sepsis in a newborn cohort including preterm newborns has not been investigated. We aimed to investigate the value of pro-ADM as a new marker by comparing it with conventional markers in neonatal sepsis (NS).. Participants were stratified into three groups; proven sepsis (Group 1a), clinical sepsis (Group 1b), and the control group (Group 2), which consisted of newborns of matched gestational age and birth weight. Sequential measurements of white blood cell count, C-reactive protein (CRP), interleukin-6 (IL-6), and pro-ADM were compared.. A total of 76 patients with NS (31 with proven sepsis and 45 with clinical sepsis) and 52 healthy controls were enrolled. Mean baseline serum levels of CRP, IL-6, and pro-ADM were significantly higher in both Group 1a and Group 1b as compared with healthy controls (P < 0.001 for both). Although mean baseline CRP and IL-6 levels were similar between groups, mean baseline pro-ADM level was higher in the proven sepsis group than in the clinical sepsis group (P < 0.001).. The use of pro-ADM in combination with other acute-phase reactants such as CRP and IL-6 for the diagnosis and follow-up of patients with NS has high sensitivity and specificity.

Topics: Adrenomedullin; Adult; Analysis of Variance; Biomarkers; Birth Weight; C-Reactive Protein; Case-Control Studies; Chi-Square Distribution; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Leukocyte Count; Male; Predictive Value of Tests; Prognosis; Protein Precursors; Sensitivity and Specificity; Sepsis; Time Factors; Up-Regulation; Young Adult

The purpose of this study was to evaluate whether adrenomedullin concentrations in the early 2nd-trimester amniotic fluid predict preterm delivery or fetal growth at birth.. The adrenomedullin concentrations in early 2nd-trimester amniotic fluid were measured in 70 pregnancies with term delivery and in 3 pregnancies with preterm delivery. Total and free adrenomedullin concentrations were measured from early 2nd-trimester amniotic fluid samples using an immunoradiometric assay.. The amniotic fluid total adrenomedullin concentrations in women with preterm delivery were significantly higher (129.7 +/- 19.6 fmol/ml) than those in women with term delivery (92.5 +/- 28.2 fmol/ml; p < 0.05). There were no significant differences for amniotic fluid free adrenomedullin concentrations and free/total adrenomedullin ratios between the two groups. Total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid showed an inverse correlation both with birth weight (r = 0.27, p < 0.05, and r = 0.21, p < 0.05) and height (r = 0.30, p < 0.05, and r = 0.28, p < 0.05). There were no correlations between placental weight and total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid.. These results suggest that adrenomedullin concentrations in the early 2nd-trimester amniotic fluid might be related to further in utero fetal growth and that high levels of adrenomedullin in the early 2nd-trimester amniotic fluid may be involved in the occurrence of preterm delivery.

Topics: Adrenomedullin; Adult; Amniotic Fluid; Biomarkers; Birth Weight; Body Height; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Obstetric Labor, Premature; Peptides; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Second

To evaluate whether maternal and fetal plasma adrenomedullin levels in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants.. Maternal and fetal circulating adrenomedullin levels were compared between 62 pregnancies with AGA (43 delivered vaginally and 19 delivered by elective cesarean section) and 28 pregnancies with SGA (20 delivered vaginally and 8 delivered by elective cesarean section) at birth. Plasma adrenomedullin levels were measured from maternal and cord venous blood samples using a radioimmunoassay. Umbilical artery blood pH was also measured.. There were no significant differences for maternal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. There were also no significant differences for fetal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. In the AGA group delivered vaginally, fetal mature/total adrenomedullin ratio (mean +/- standard error, 16.6 +/- 0.7%) was significantly higher than the maternal ratio (13.8 +/- 0.6%) (p < 0.05). In the SGA group delivered vaginally, fetal mature/total adrenomedullin ratio (18.5 +/- 1.0%) was also significantly higher than the maternal ratio (14.5 +/- 0.6%) (p < 0.05). There was no significant difference in umbilical artery blood pH among the groups.. These results suggest that maternal and fetal plasma circulating adrenomedullin levels may play a role in maternal and fetal cardiovascular adaptation during delivery in pregnancies with both AGA and SGA infants.

Topics: Adrenomedullin; Adult; Birth Weight; Cesarean Section; Delivery, Obstetric; Female; Fetal Blood; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Infant, Small for Gestational Age; Peptides; Pregnancy; Umbilical Arteries

To examine whether adrenomedullin, a novel vasoactive peptide produced by the placenta, participates in the uteroplacental hemodynamic alterations in intrauterine growth restriction, we studied the correlation between adrenomedullin levels and fetoplacental blood flow.. Maternal and umbilical blood samples were collected in pregnancies complicated by intrauterine growth restriction with abnormal umbilical artery Doppler findings and in control pregnancies. Adrenomedullin levels were measured by means of a specific radioimmunoassay, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries.. Mean adrenomedullin values in umbilical plasma were higher (P <.05) in patients with intrauterine growth restriction (63.7 +/- 34.2 pg/mL; n = 16) than in control subjects (38.1 +/- 14.8 pg/mL; n = 16). A significant correlation was found between maternal adrenomedullin levels and umbilical artery pulsatility index. Moreover, fetal adrenomedullin concentrations correlated negatively with middle cerebral artery pulsatility index and positively with umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio.. This study provides evidence that adrenomedullin is increased in fetuses with intrauterine growth restriction in response to reduced uteroplacental blood flow and suggests that it may participate in the fetal hemodynamic modifications.

Topics: Adrenomedullin; Adult; Birth Weight; Blood Flow Velocity; Female; Fetal Growth Retardation; Gestational Age; Humans; Peptides; Placental Insufficiency; Pregnancy; Ultrasonography, Prenatal

The purpose of the present study was to investigate whether placental immunohistochemical adrenomedullin expression in normal normotensive pregnancies is different from that in pregnancies with pre-eclampsia. Placental tissues were obtained from seven normal normotensive pregnancies and 12 pregnancies with pre-eclampsia. The intensity of adrenomedullin staining in syncytiotrophoblasts was evaluated by means of immunohistochemistry and the ratio of the number of intact tertiary villi to that of total tertiary villi (intact/total villi ratio) was determined. The intensity of adrenomedullin expression in the placenta obtained from pregnancies with pre-eclampsia was significantly decreased compared with expression in placentas from uncomplicated normotensive pregnancies (P < 0.005). The intact/total villi ratio in placentas obtained from pregnancies with pre-eclampsia was significantly lower than that in placentas from normal normotensive pregnancies (P < 0.0001). In the amnion and extravillous trophoblast cells in both groups, no difference for the intensity of adrenomedullin expression was noted. These results suggest that adrenomedullin synthesis in the villous syncytiotrophoblasts is decreased in pregnancies with pre-eclampsia.

Topics: Adrenomedullin; Adult; Amnion; Antihypertensive Agents; Birth Weight; Female; Gestational Age; Humans; Immunoenzyme Techniques; Organ Size; Peptides; Placenta; Pre-Eclampsia; Pregnancy