Establishment of metanephros transplantation in mice highlights contributions by both nephrectomy and pregnancy to developmental progression

Background: It has been demonstrated that embryonic kidneys (metanephroi) xenotransplanted into the omentum of adult recipients continue to develop and display immune protection due to their more nave immune presentation. To date, this has been achieved using rat, pig and human metanephroi, with unilateral nephrectomy (UNX) of recipient rats a requisite of renal development. The aim of this study was to adapt this approach for use in mice and examine the parameters affecting successful onward development in this species. Methods: Metanephroi at embryonic age (E) 13.5 were transplanted either onto the body wall, abdominal fat pads or omentum of recipient isogenic C57/Bl6 mice using either sutures or polyglycolic acid mesh. Having established greatest success with polyglycolic acid mesh on the body wall, E12.5 and 15.5 days metanephroi from C57/Bl6 mice were then transplanted onto the body wall of control (non-pregnant non-UNX), UNX or 12.5 days post-coitum pregnant isogenic recipients. After 7 days, implanted tissue was harvested and examined using histology and immunohistochemistry for markers of renal maturation. The mean number of S-shaped bodies and glomeruli per section were recorded and statistically analysed for significant differences between all recipient groups and untransplanted metanephroi. The degree of development was scored qualitatively. Results: Transplanted E12.5 metanephroi developed S-shaped bodies and glomeruli in all recipient groups, although there were statistically higher numbers of S-shaped bodies in UNX (n = 2) and pregnant recipients (n = 9) than in control recipients (n = 4). Continued development, as indicated by mature vascularized glomeruli, was only observed in those E15.5 metanephroi transplanted into pregnant recipients (n = 11) with a 15.5-fold increase in S-shaped bodies and 4-fold increase in glomeruli compared with control transplants (n = 12). Conclusions: We have successfully established metanephros transplantation in mice and demonstrated enhancement of onward development of E12.5 metanephroi in response to both pregnancy and UNX. Using E15.5 metanephroi, continued development only occurred in pregnant recipients, implying pregnancy provides an environment conducive to continued organogenesis. This murine assay, when coupled with transgenically-tagged strains of mice, will allow the investigation of the relative contribution of donor and recipient cells to this process. Copyright (C) 2005 S. Karger AG, Basel.

Population pharmacokinetics of metformin in late pregnancy

The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes, 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method, A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in'NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0. 1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 ka (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, ea, effects on neonatal obesity and insulin resistance, remain unknown.

Risk factors for pregnancy and childbearing in single young women: Evidence from the Australian Longitudinal Study on Women's Health

This study investigated psychosocial predictors of early pregnancy and childbearing in single young women, consistent with the Eriksonian developmental perspective. Two mail-out surveys assessing reproductive behaviour and sociodemographic, education/competence, psychosocial well-being, and aspiration factors were completed 4 years apart by 2635 young women, aged 18 to 20 when first surveyed. Young women in the emerging adulthood'' developmental period were selected from the Australian Longitudinal Study on Women's Health. Longitudinally, lower investment in education over low-status paid work, experiencing unemployment, greater psychosocial distress, stress and alcohol use, and high family aspirations combined with low vocational aspirations were risk factors for early single pregnancy and childbearing. Several mediational relationships also existed between these predictor variables. It was concluded that psychosocial factors play an important role in understanding early pregnancy and childbearing in single young Australian women, and that the findings provide some support for investigating early pregnancy and childbearing from an Eriksonian developmental perspective.

Socioeconomic position, cognitive function, and clustering of cardiovascular risk factors in adolescence: Findings from the Mater University Study of Pregnancy and its outcomes

Objectives: The objectives of this study were to examine the extent of clustering of smoking, high levels of television watching, overweight, and high blood pressure among adolescents and whether this clustering varies by socioeconomic position and Cognitive function. Methods: This study was a cross-sectional analysis of 3613 (1742 females) participants of an Australian birth cohort who were examined at age 14. Results: Three hundred fifty-three (9.8%) of the participants had co-occurrence of three or four risk factors. Risk factors clustered in these adolescents with a greater number of participants than would be predicted by assumptions of independence having no risk factors and three or four risk factors. The extent of clustering tended to be greater in those from lower-income families and among those with lower cognitive function. The age-adjusted ratio of observed to expected cooccurrence of three or four risk factors was 2.70 (95% confidence interval [Cl], 1.80-4.06) among those from low-income families and 1.70 (95% Cl, 1.34-2.16) among those from more affluent families. The ratio among those with low Raven's scores (nonverbal reasoning) was 2.36 (95% Cl, 1.69-3.30) and among those with higher scores was 1.51 (95% Cl, 1.19-1.92); similar results for the WRAT 3 score (reading ability) were 2.69 (95% Cl, 1.85-3.94) and 1.68 (95% Cl, 1.34-2.11). Clustering did not differ by sex. Conclusion: Among adolescents, coronary heart disease risk factors cluster, and there is some evidence that this clustering is greater among those from families with low income and those who have lower cognitive function.

Acupressure for the in-patient treatment of nausea and vomiting in early pregnancy: A randomized control trial

Objective: The purpose of this study was to evaluate the efficacy of acupressure at the P6 point for the in-patient treatment of severe nausea and vomiting in early pregnancy. Study design: This was a prospective single-blind randomized control trial that involved 80 patients with nausea and vomiting plus ketonuria before 14 weeks of gestation. Results: There was no difference between length of stay, amount of medication, or fluid required between the acupressure and placebo groups, although acupressure reduced the number of patients who stayed >= 4 nights in the hospital. Acupressure was well tolerated and not associated with an increase in perinatal morbidity or death. Conclusion: The use of acupressure Lit the P6 point does not reduce the amount of antiemetric medication that is required, the requirement for intravenous fluid, and median duration of inpatient stay more than the use of placebo. A small reduction was seen in the number of women who required >= 4 days in the hospital. (c) 2006 Mosby, Inc. All rights reserved.

Psychosocial risk factors for pregnancy risk-taking in young women in emerging adulthood: Evidence from the Australian Longitudinal Study on Women's Health

This study represents the first longitudinal investigation of distal psychosocial predictors of pregnancy risk-taking in young Australian women. Participants were from the Australian Longitudinal Study on Women's Health. Two mail-out surveys assessing sociodemographic, education/competence, psychosocial wellbeing, and aspiration/identity factors, were completed at ages 18 and 22 by 1647 young women in emerging adulthood, and a third survey assessing pregnancy risk-taking behaviour was completed by a subsample of 90 young women at age 24. Higher psychosocial distress at age 22 was a risk factor for pregnancy risk-taking at age 24 (beta=0.29-0.38). Post hoc analyses suggested that the strongest component of psychosocial distress when predicting pregnancy risk-taking was higher depressive symptoms (beta=0.44-0.68). Demographic, education, unemployment, and future aspirations factors at age 18 and 22 were unrelated to pregnancy risk-taking at age 24.

Maternal health during pregnancy and perinatal mortality in Bangladesh: evidence form a large-scale community-based clinical trial

Perinatal mortality is very high in Bangladesh. In this setting, few community-level studies have assessed the influence of underlying maternal health factors on perinatal outcomes. We used the data from a community-based clinical controlled trial conducted between 1994 and 1997 in the catchment areas of a large MCH/FP hospital located in Mirpur, a suburban area of Dhaka in Bangladesh, to investigate the levels of perinatal mortality and its associated maternal health factors during pregnancy. A total of 2007 women were followed after recruitment up to delivery, maternal death, or until they dropped out of the study. Of these, 1584 who gave birth formed our study subjects. The stillbirth rate was 39.1 per 1000 births [95% confidence interval (CI) 39.0, 39.3] and the perinatal mortality rate (up to 3 days) was 54.3 per 1000 births [95% CI 54.0, 54.6] among the study population. In the fully adjusted logistic regression model, the risk of perinatal mortality was as high as 2.7 times [95% CI 1.5, 4.9] more likely for women with hypertensive disorders, 5.0 times [95% CI 2.3, 10.8] as high for women who had antepartum haemorrhage and 2.6 times [95% CI 1.2, 5.8] as high for women who had higher haemoglobin levels in pregnancy when compared with their counterparts. The inclusion of potential confounding variables such as poor obstetric history, sociodemographic characteristics and preterm delivery influenced only marginally the net effect of important maternal health factors associated with perinatal mortality. Perinatal mortality in the study setting was significantly associated with poor maternal health conditions during pregnancy. The results of this study point towards the urgent need for monitoring complications in high-risk pregnancies, calling for the specific components of the safe motherhood programme interventions that are designed to manage these complications of pregnancy.

"Making it all normal": the role of the Internet in problematic pregnancy

Women are actively encouraged to educate themselves about pregnancy from formal sources (e.g., information leaflets, antenatal classes, books). In addition, informal stories of pregnancy and birth are routinely told between women. However, increased prenatal testing means that more fetuses are diagnosed with abnormalities, shifting the information requirements during pregnancy. Traditional sources of information cannot cover all possible outcomes, and the Internet is beginning to fill this gap. In this article, we draw from interviews about experiences of antenatal screening and pregnancy to explore how the Internet provides a unique resource for problematic pregnancies. It allows access to information about rarer conditions beyond standard pregnancy texts, as well as personal narratives about conditions. Learning how others have coped or are coping in similar situations can help alleviate feelings of isolation, and also places women back in a familiar territory of shared pregnancy narratives.