Glomerular and tubular effects of nitric oxide (NO) are regulated by angiotensin II (Ang II) in an age-dependent manner through activation of both angiotensin receptors (AT1Rs and AT2Rs) in conscious lambs.

Renin-angiotensin (RAS) and nitric oxide (NO) systems and the balance and interaction between them are considered of primary importance in maintaining fluid and electrolyte homeostasis. It has been suggested that the effects of NO may be modulated at least in part by the angiotensin (Ang) II, yet the roles of angiotensin receptor type 1 (AT1R) and type 2 (AT2R) are not well understood. Even though both Ang II and NO are elevated at birth and during the newborn period, their contribution to the adaptation of the newborn to life after birth as well as their physiological roles during development are poorly understood. The aim of this study was to determine if NO regulation of renal function during postnatal maturation is modulated by Ang II through activation of AT1R or AT2R or both receptors. Glomerular and tubular effects of either AT1R selective antagonist ZD 7155, AT2R selective antagonist PD 123319, and both antagonists ZD 7155 plus PD 123319, were measured in 1- (N = 9) and 6-week-old (N = 13) conscious, chronically instrumented lambs before and after removal of endogenous NO with L-arginine analogue, L-NAME. Two-way analysis of variance (ANOVA) procedures for repeated measures over time with factors age and treatment were used to compare the effects of the treatments on several glomerular and tubular variables in both groups. This study showed that L-NAME infusion after pre-treatment with ATR antagonists did not alter glomerular function in 1- or 6-week-old lambs. NO effects on electrolytes handling along the nephron during postnatal development were modulated by Ang II through AT1R and AT2R in an age-dependent manner. Selective inhibition of AT1R and AT2R increased excretion of Na+, K+, and Cl- in 6- but not in 1-week-old lambs. In 6-week-old lambs, urinary flow rate increased by 200%, free water clearance increased by 50%, and urine osmolality decreased by 40% after L-NAME was added to the pre-treatment with ZD 7155 plus PD 123319. When L-NAME was added either to ZD 7155 or PD 123319, the same trend in the alterations of these variables was observed, albeit to a lower degree. In conclusion, in conscious animals, during postnatal maturation, Ang II modulates the effects of NO on glomerular function, fluid, and electrolyte homeostasis through AT1Rs and AT2Rs in an age-dependent manner. Under physiological conditions, AT2Rs may potentiate the effects of AT1R, providing evidence of a crosstalk between ATRs in modulating NO effects on fluid and electrolyte homeostasis during postnatal maturation. This study provides new insights on the regulation of renal function during early postnatal development showing that, compared with later in life, newborns have impaired capacity to regulate glomerular function, water, and electrolyte balance.

Recall of Prenatal Counselling Among Obese and Overweight Women from a Canadian Population: A Population Based Study.

Objective The objective of this study was to evaluate the recall of prenatal counselling received among overweight and obese women in primary care settings. Methods A sample of 1996 women with singleton, term deliveries and pre-pregnancy BMI >18.5 kg/m2 were identified from the All Our Babies pregnancy cohort. Information on socio-demographic characteristics and women's experiences with prenatal counselling on nutrition, vitamin and mineral supplements, exercise, weight gain, employment, alcohol and drug use, and smoking during pregnancy were collected through questionnaires administered at <25 weeks and 34-36 weeks gestation. Multivariable logistic regression analyses explored the associations between pre-pregnancy BMI and the domains of prenatal counselling, controlling for confounders. Results Women reported high levels of comfort asking questions and satisfaction with their health care provider. Women reported getting information about nutrition (69.3%), weight gain (67.8%), exercise (64.4%), vitamins and minerals supplementation (86.1%). Obese women (211, 10.6%) were more likely than normal weight women (1313, 65.8%) to be Caucasian (p = 0.004), less educated (p = 0.001), and to have been born or lived in Canada for at least 5 years (p = 0.01). There was no difference in the prenatal advice received on nutrition, weight gain and exercise in pregnancy between obese, overweight, and normal weight women. Conclusions for Practice Pre-pregnancy BMI did not appear to influence the recall of prenatal counselling women receive in community health care centers. Given the importance of nutrition and weight gain during pregnancy, and guidelines for weight gain based on pre-pregnancy BMI, there are missed opportunities in knowledge exchange between women and providers in the prenatal period.

Biomarkers of spontaneous preterm birth: a systematic review of studies using multiplex analysis.

OBJECTIVE: Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. MATERIALS AND METHODS: Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal biomarkers associated with PTB published from January 2005 to March 2014. RESULTS: Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies) followed by MIP-1ß, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. CONCLUSION: By this systematic review, we conclude that multiplex assays are a potential technological advancement for identifying biomarkers of PTB, although no single or combination of biomarkers could be identified to predict PTB risk.

Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors.

BACKGROUND: Evidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development. METHODS: The renal effects of the selective antagonist to AT1R, ZD 7155 and to AT2R, PD 1233319 were evaluated in two groups of conscious chronically instrumented lambs aged ~ one week (N = 8) and ~ six weeks (N = 10). Two experiments were carried out in each animal and consisted of the assessment of renal variables including glomerular and tubular function, for 30 min before (Control) and 60 min after infusion of ZD 7155 and PD 123319, respectively. Statistical significance was determined using parametric testing (Student t-test, analysis of variance ANOVA) as appropriate. RESULTS: ZD 7155 infusion was associated with a significant decrease in glomerular filtration rate and filtration fraction at one but not six weeks; urinary flow rate decreased significantly in older animals, whereas sodium excretion and free water clearance were not altered. There was an age-dependent effect on potassium handling along the nephron, potassium excretion decreasing after ZD 7155 infusion in younger but not in older lambs. PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group. CONCLUSIONS: These results provide evidence to support an important role for AT1Rs in mediating the renal effects of angiotensin II during postnatal maturation in conscious developing animals. In contrast to a role for AT2Rs later in life, there appears to be no role for AT2Rs in influencing the renal effects of Angiotensin II in the postnatal period.

Pre-pregnancy body mass index (BMI) and macrosomia in a Canadian birth cohort.

OBJECTIVE: To compare demographic characteristics and maternal, fetal, neonatal, and pregnancy outcomes of term macrosomic infants of obese and non-obese mothers. METHODS: A sample of 1996 singleton, term deliveries was drawn from the All Our Babies Cohort, a prospective, community-based pregnancy cohort. Maternal self-reported socio-demographic and anthropometric information was linked to the clinical data on pregnancy and birth events abstracted from electronic health records. Demographic, obstetrical characteristics and maternal, fetal, neonatal, and pregnancy outcomes of macrosomic infants in obese, overweight, and normal weight women were compared. Multinomial regression analysis assessed the risk factors of macrosomia in primiparous and multiparous women stratified by maternal pre-pregnancy BMI, controlling for confounding variables. RESULTS: Macrosomia affected 10% of pregnancies in the study. Mothers whose infants were macrosomic were more likely to be Caucasian, obese, have had previous deliveries, undergo induction of labour and delivery by emergency C-section, particularly for labour abnormalities. Macrosomic infants were more likely to be delivered postdates, have meconium stained liquor and require resuscitation at birth. There were no significant differences in birth and neonatal outcomes of macrosomic pregnancies between obese, overweight and normal weight women. Pre-pregnancy BMI and gestational age at delivery were risk factors for macrosomia in all women. Ethnicity and history of delivery of a macrosomic infant were additional independent risk factors in multiparas. CONCLUSIONS: Obesity in pregnancy increases the risk of delivery of a macrosomic infant in both primiparous and multiparous women. The maternal, fetal and neonatal outcomes of macrosomic pregnancies are similar in obese and normal weight women.

Maternal perceptions of underweight and overweight for 6-8†years olds from a Canadian cohort: reporting weights, concerns and conversations with healthcare providers.

OBJECTIVES: The majority of mothers do not correctly identify their child's weight status. The reasons for the misperception are not well understood. This study's objective was to describe maternal perceptions of their child's body mass index (BMI) and maternal report of weight concerns raised by a health professional. DESIGN: Prospective, community-based cohort. PARTICIPANTS: Data were collected in 2010 from 450 mothers previously included in a longitudinal birth cohort. Mothers of children aged 6-8 years reported their child's anthropometric measures and were surveyed concerning their opinion about their child's weight. They were also asked if a healthcare provider raised any concerns regarding their child's body weight. Child BMI was categorised according to the WHO Growth Charts adapted for Canada. Descriptive statistics and bivariate analyses were used to evaluate mothers' ability to correctly identify their children's body habitus. RESULTS: 74% of children had a healthy BMI, 10% were underweight, 9% were overweight and 7% were obese. 80%, 89% and 62% of mothers with underweight, overweight and obese children, respectively, believed that their child was at the right weight. The proportion of mothers who recalled a health professional raising concerns about their child being underweight, overweight, and obese was low (12.5%). CONCLUSIONS: The majority of mothers with children at unhealthy weights misclassified and normalised their child's weight status, and they did not recall a health professional raising concerns regarding their child's weight. The highest rates of child body weight misclassification occurred in overweight children. This suggests that there are missed opportunities for healthcare professionals to improve knowledge exchange and early interventions to assist parents to recognise and support healthy weights for their children.

Maternal microbiome - A pathway to preterm birth.

Despite great medical advances in preventing maternal and infant mortality in the past century, one issue remains unresolved: why do so many women give birth prematurely? A major new field of human microbiome studies has begun to shed light on the impact of microbes (of both the commensal and pathogen varieties) on pregnancy outcomes. Recent advances in next-generation sequencing and metagenomic analysis have revealed that maternal microbiomes at a variety of niches including the oral, vaginal, gut, cervical, and even the placenta itself govern pregnancy outcomes. In this review, we describe how alterations in the microbial biomasses impact preterm birth and we discuss the major research questions concerning the cause and/or interdependent relationships between microbiome, infection, and preterm delivery.

Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.

The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17-23 (sampling time point 1, T1) and 27-33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care.

The Influence of Back Pain and Urinary Incontinence on Daily Tasks of Mothers at 12 Months Postpartum.

OBJECTIVE: The present study examined back pain (BP) and/or urinary incontinence (UI) impact on the ability to perform daily tasks at 12 months after childbirth in healthy reproductive women who sought maternity care in community based family practice clinics. METHODS: This study is a secondary analysis from the All Our Babies Study, a prospective, community-based pregnancy cohort in Calgary, Alberta. Maternal self-reported information on demographics, lifestyle, experiences with pregnancy and childbirth, occurrence of BP, UI and consequent impairment of daily tasks were collected by questionnaires administered before 25 weeks, at 34-36 weeks gestation and at 4 and 12 months postpartum. The occurrence and severity of BP and UI at one year after childbirth was assessed using descriptive and bivariate analyses. Logistic regression models examined the association between demographic and obstetrical variables and the severity of functional impairment due to UI and BP. RESULTS: From 1574 women with singleton pregnancies included in the study, 1212 (77%) experienced BP, 773 (49%) UI, and 620 (40%) both BP and UI. From the 821 women reporting impairment of daily tasks due to BP, 199 (24 %) were moderately and 90 (11%) severely affected with the remainder, 532 (64%) being mildly affected. From 267 women with functional impairment due to UI, 52 (19%) reported moderately to severe impairment in their ability to perform daily tasks. Obesity and parity were risk factors for impairment of daily functioning due to BP, whereas obesity and vaginal delivery increased the risk of moderate to severe impairment due to UI. CONCLUSIONS: BP and UI are common occurrences 1 year after childbirth. Maternal performance of daily tasks and women's health and quality of life are more often impaired due to BP than UI. Our study brings new evidence of the risk factors that predict severity and impact of these conditions on women functioning at 12 months postpartum.

Do angiotensin type 2 receptors modulate haemodynamic effects of type 1 receptors in conscious newborn lambs?

INTRODUCTION AND HYPOTHESIS: It was hypothesized that in the immediate newborn period, when the renin-angiotensin system (RAS) is activated, angiotensin type 2 receptors (AT2Rs) buffer the haemodynamic effects of angiotensin type 1 receptors (AT1Rs), as occurs in adult animals when the RAS is activated. MATERIALS AND METHODS: Arterial (systolic, diastolic, and mean) pressures (SAP, DAP, MAP), mean venous pressures (MVP) and renal blood flows (RBF) were measured in conscious, chronically instrumented lambs aged ~1 (8±2 days, N=8) and 6 weeks (41±4 days, N=11). In each animal, measurements were made before and after administration of the selective AT1R antagonist ZD 7155 (experiment one) and the selective AT2R antagonist PD123319 (experiment two) as well as both antagonists, ZD 7155 and PD 123319 (experiment three). RESULTS: Haemodynamic responses to combined inhibition of both AT1Rs and AT2Rs were similar to inhibition of AT1Rs alone: there was a significant decrease in SAP, DAP, and MAP and a significant increase in RBF within minutes of concomitant administration of ZD 7155 and PD 123319 in both age groups. These responses were similar to responses to ZD 7155 alone, whereas PD 123319 alone did not alter any of the measured variables. CONCLUSIONS: AT2Rs do not counterbalance the pressor and renal vasoconstrictor effects elicited by activation of AT1Rs in the immediate newborn period. During this time, AT1Rs appear to predominate in eliciting the haemodynamic effects of angiotensin II (ANG II), whereas the role of the upregulated AT2Rs remains elusive.

Angiotensin receptors modulate the renal hemodynamic effects of nitric oxide in conscious newborn lambs.

This study aimed to elucidate the roles of both angiotensin II (ANG II) receptors - type 1 (AT1Rs) and type 2 (AT2Rs) - separately and together in influencing hemodynamic effects of endogenously produced nitric oxide (NO) during postnatal development. In conscious, chronically instrumented lambs aged ~1 week (8 ± 1 days, N = 8) and ~6 weeks (41 ± 2 days, N = 8), systolic, diastolic, and mean arterial pressure (SAP, DAP, MAP) and venous pressure (MVP), renal blood flow (RBF), and renal vascular resistance (RVR) were measured in response to the l-arginine analog, l-NAME after pretreatment with either the AT1R antagonist, ZD 7155, the AT2R antagonist, PD 123319, or both antagonists. The increase in SAP, DAP, and MAP by l-NAME was not altered by either ATR antagonist in either age group. The increase in RBF after l-NAME was, however, altered by both ATR antagonists in an age-dependent manner, which was mediated predominantly through AT2Rs in newborn lambs. These findings reveal that there is an age-dependent interaction between the renin-angiotensin (RAS) and the NO pathway in regulating renal but not systemic hemodynamics through both ATRs, whereas AT2Rs appear to be important in the renal hemodynamic effects of NO early in life.

Regulation of sPLA2-IID in Human Decidua: Insights Into the Complexity of the Prostaglandin Pathway in Labor.

Prostaglandins are implicated in the labor process, yet the precise role and regulation of the prostaglandin pathway remains to be elucidated. The first step in the pathway is cleavage of membrane phospholipids by phospholipase A2 (PLA2). Previous work demonstrated upregulation of secretory PLA2 (sPLA2)-IIA with labor in human myometrium, and recent evidence shows that there are numerous PLA2 isoforms. The present study investigates the potential of additional sPLA2 isoforms during pregnancy and labor. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry were used to determine sPLA2 expression and localization. Results show the presence of sPLA2-IID in amnion, chorion, placenta, decidua, and myometrium. Expression of sPLA2-IID in decidua was significantly decreased in term labor compared to nonlabor patients, whereas no significant labor-associated changes were observed in other gestational tissues. Secretory PLA2-IID was localized within chorion fibroblasts, placenta trophoblasts, decidual cells, and in myometrial smooth muscle cells. In primary decidual cell cultures, interleukin (IL) 10 (IL-10) increased sPLA2-IID messenger RNA (mRNA) expression, while IL-1ß had no effect on sPLA2-IID mRNA expression. In conclusion, decreased expression of sPLA2-IID in the decidua at labor indicates that it is unlikely to contribute to increased prostaglandin production during labor. However, increased expression of sPLA2-IID, induced by IL-10, suggests that sPLA2-IID may play an important anti-inflammatory role at the maternal-fetal interface. Nevertheless, precise functions of sPLA2-IID within the human uterus remain to be determined.