Reducing stillbirths: screening and monitoring during pregnancy and labour

Background

Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality.

Methods

The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome.

Results

We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress.

Conclusion

There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit.

     

The Impact of Healthcare Issues on the Future of the Nursing Profession: The Resulting Increased Influence of Community-Based and Public Health Nursing

Several key issues, such as the necessity for cost containment, role conflicts between healthcare professions, nursing shortages, and organizational difficulties of healthcare organizations, significantly influence current healthcare delivery. These circumstances, which constitute a compelling need for responsive and effective change, are examined in terms of their impact upon the nursing profession. A review of the referenced journals and textbooks reveals that national nursing efforts will shift from acute care hospital-oriented provisions to community-based public health orientations. This evolution will result in improved health outcomes, less need for tertiary treatment, and savings for hospitals and insurance companies.     

Accumulation of PDGF+ cells and internalisation of the PDGF receptor at myotendinous junction following modified hindlimb muscle use in the rat

Morphological observations have shown previously that myotendinous junctions (MTJs) are sites where the associations between the cytoskeleton and the cell membrane are extensively remodelled during muscle growth and modified mechanical loading. The platelet derived growth factor (PDGF) molecule has been shown to induce cytoskeletal remodelling at focal contact sites of myoblasts in culture, the analogous structures of MTJs. The goals of the study were to determine whether PDGF is synthesised by mononuclear cells and whether PDGF receptors are internalised at the MTJs of the soleus muscle experiencing reloading. We also examined whether ED2⁺ macrophages that are nonphagocytic and activated inflammatory cells at MTJs during reloading secrete PDGF. Results obtained by immunohistochemistry showed that there was an increase in the number of cells expressing PDGF at remodelling MTJs and that the ED2⁺ macrophage population does not express PDGF at MTJs. According to morphological criteria, fibroblasts would be the logical candidates to secrete PDGF molecules near MTJs. Furthermore, the modification in muscle loading resulted in internalisation of PDGF receptors concentrated at the MTJ which accumulated predominantly around muscle nuclei. The enrichment of PDGF receptors and PDGF⁺ cells at MTJs and the internalisation of PDGF receptors during remodelling of MTJs suggest that PDGF may influence remodelling of MTJs following modified muscle use.     

Recognition and management of falciparum malaria

Falciparum malaria is a serious parasitic infection that, if left untreated, can give rise to a range of life‐threatening complications. Prompt recognition depends on a high index of suspicion and a detailed history identifying possible malaria risk factors. Symptoms and signs, apart from periodic fever in some cases, are typically non‐specific. Even in cases of severe falciparum malaria with vital organ involvement, the differential diagnosis can be broad. The gold standard diagnostic test is blood film microscopy but antigen detection tests have become available as an alternative. Other laboratory tests can, together with the history and examination findings, help confirm the diagnosis and provide data relating to the nature and severity of complications. Management of malaria involves prompt administration of effective antimalarial drugs and prevention or amelioration of complications such as coma (cerebral malaria), renal failure and acidosis. Oral treatment is usually given to patients with uncomplicated malaria while therapy should be administered parenterally in severe cases. Conventional drugs such as quinine are still useful but the artemisinin derivatives are rapidly acting antimalarial drugs that are increasingly used as first‐line therapy in tropical countries. Most adjunctive therapies assessed specifically for their effectiveness against complications have proved disappointing but some (such as prophylactic phenobarbitone and exchange transfusion) can complement generic management protocols that remain the cornerstone of intensive care for the severely ill patient with malaria.     

Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P 0.05.RESULTS: There were significant differences in age(P 0.001), weight(P 0.001), and body mass index(P 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-N-oxide(TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.     

The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds.

In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 89, 4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a single TEF value (0.00003) for all relevant mono-ortho-substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non-dioxin-like aryl hydrocarbon receptor agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (TEQ) approach to abiotic matrices, such as soil, sediment, etc., for direct application in human risk assessment. This is problematic as the present TEF scheme and TEQ methodology are primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden.     

Evaluation of three psychologic interventions to reduce anxiety during MR imaging

The authors compared the effectiveness of three anxiety-reducing interventions for patients undergoing magnetic resonance imaging. Each of 50 subjects was randomly assigned to one of the interventions. Intervention 1 involved provision of information about the imager and nature of the examination. Intervention 2 included information and counseling. Intervention 3 included information and a 12-minute relaxation exercise. Anxiety levels were measured by means of a 20-item questionnaire before and after imaging. The latter provided a retrospective report of anxiety experienced during imaging. Patients in intervention group 3 showed significantly less increase in anxiety compared with those in groups 1 and 2. Overall, only patients who participated in intervention 1 showed a significant increase in anxiety during imaging. When anxiety levels experienced before and during the examination were compared, with the focus on each questionnaire item for each group, those in group 1 showed a significant increase in anxiety on eight of 20 items; those in group 2, three items; and those in group 3, none. Psychologic preparation that includes relaxation strategies is more effective than provision of information alone.     

Fast-field-echo MR imaging with Gd-DTPA: physiologic evaluation of the kidney and liver

To determine if magnetic resonance imaging with Gd-DTPA could be used to assess renal and hepatic perfusion and possibly function, a fast-field-echo technique was used to perform sequential imaging of the kidney and liver of five subjects. Sixteen 3-second images of the same section were obtained at 13-second intervals immediately after Gd-DTPA administration, and again at 30 or 50 minutes after injection. From these images, curves of renal and hepatic signal versus time were generated. In each case the renal signal intensity peaked within 2 minutes and decreased to 60% or less by 3.4 minutes, and 35% or less by 50 minutes. Hepatic curves peaked within 2 minutes and approached initial levels by 30 minutes. These results suggest that transit and clearance of the contrast agent can be imaged by this technique.