Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome.

OBJECTIVES: To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening. METHODS: State-wide data collections of prenatal screening and diagnostic tests were linked to all Victorian births and pregnancy terminations for birth defects. RESULTS: Overall, 52% of women had a prenatal test (65 692/126 305); screening (44.9%), diagnostic testing (3.9%), or both (3.2%). Uptake of diagnostic testing was 71.4% (2390/3349) after an increased risk screen result, and 2.5% (1381/54 286) after a low risk result. Variation in uptake of diagnostic testing reduced the effectiveness of the screening program by 11.2%: from 87.4% (sensitivity - 125/143) to 76.2% (prenatal diagnoses of Down syndrome - 109/143). In both the increased and low risk groups, uptake was influenced by absolute numerical risk, as well as by the change in numerical risk from a priori risk. CONCLUSIONS: This comprehensive follow-up demonstrates clearly that numerical risk is being used to aid in decision making about confirmatory diagnostic testing. Collectively, these fundamental individual decisions will impact on the overall effectiveness of screening programmes for Down syndrome.

Going down a different road: first support and information needs of families with a baby with Down syndrome.

OBJECTIVE: To explore the experiences of families with a baby with Down syndrome at the time of diagnosis, and their preferences for information and support in the early period after diagnosis. DESIGN, SETTING AND PARTICIPANTS: A qualitative, interview-based study of 18 families living in Victoria with a child with Down syndrome born between 2002 and 2004 who had not been diagnosed with the syndrome before birth. Interviews were transcribed verbatim and interpretive content analysis was undertaken. RESULTS: Parental coping with the unexpected diagnosis of Down syndrome in their infant was influenced by the time interval between birth and disclosure of clinical suspicion of Down syndrome, the level of certainty of the attending physician at the time of disclosure, and the time interval between disclosure of clinical suspicion and confirmation of karyotype. Initial uncertainty and a delay in the diagnosis were detrimental to parental coping, as was premature communication of the news. Perinatal complications increased parental anxiety regarding their child's condition and future. Individual communication style of midwives and physicians was a powerful predictor of parental adaptation. Parental needs for support and information were facilitated through normalising postnatal care, ensuring privacy, and providing early access to peer support and up-to-date written information. Many parents would have appreciated access to a liaison worker. CONCLUSION: The experiences of parents in this study provide practice points for improving postnatal care with minimal changes to formal service systems.

Is Down syndrome a disappearing birth defect?

OBJECTIVE: To assess trends in the prevalence of Down syndrome (DS) from 1986 to 2004 in Victoria, Australia (population approximately 5 million). STUDY DESIGN: The Victorian Birth Defects Register and the Prenatal Diagnosis Database were linked to ascertain all cases of DS. Total and birth prevalence estimates were calculated per year and presented as 3-year moving averages. RESULTS: The total number of cases of DS increased from 113 in 1986 to 188 in 2004. The number of births declined over the first decade of the study, particularly in younger women, but total numbers have fluctuated between 45 and 60 births since 1996. In women under age 35 years, total prevalence was 10/10,000 until 1997 and then increased to 12.5/10,000. In older women, total prevalence increased from 70/10,000 to 90/10,000 in this time frame. Birth prevalence declined at first but remained relatively stable in the later years of the study. The proportion of cases diagnosed prenatally increased from 3% to 60% in younger women. CONCLUSIONS: Our findings demonstrate the continuing need to devote resources to support individuals with DS and their families.

Folic acid and risk of twinning: a systematic review of the recent literature, July 1994 to July 2006.

OBJECTIVE: To assess the evidence of an association between periconceptional folic acid (FA) supplementation or fortification of foods with FA and the risk of twinning, using the Food Standards Australia New Zealand (FSANZ) framework for assessing evidence when substantiating nutrition, health and related claims on foods. DATA SOURCES: The Cochrane Library Database, MEDLINE, MEDLINE in Process, EMBASE, PubMed National Library of Medicine, and CINAHL were searched to identify systematic reviews and primary intervention and observational studies published from 1 July 1994 to 7 July 2006. STUDY SELECTION: One prospective and five retrospective cohort studies that assessed the rate of twinning in populations exposed to FA through supplementation, and six retrospective registry-based cohort studies examining twinning rates after fortification of foods with FA. DATA EXTRACTION: Two reviewers appraised eligible studies and evaluated data independently. DATA SYNTHESIS: The best maximal risk estimates of twinning after FA supplementation were an adjusted odds ratio (adjOR) of 1.26 (95% CI, 0.91-1.73) for preconceptional supplementation and dizygotic twinning and an adjOR of 1.02 (95% CI, 0.85-1.24) for overall twinning. Data from four FA fortification studies in the United States that allowed for calculation of an annual percentage increase showed a maximal annual increase in twinning rates of 4.6%. CONCLUSIONS: Overall, under the FSANZ framework, there is possible evidence for a relationship between periconceptional FA intake and increased twinning. To support this tentative relationship, more well designed, long-term follow-up studies are needed in places where fortification with FA has been introduced, focusing on dose-response and obtaining accurate data on infertility treatments.

Health behaviour modelling for prenatal diagnosis in Australia: a geodemographic framework for health service utilisation and policy development.

BACKGROUND: Despite the wide availability of prenatal screening and diagnosis, a number of studies have reported no decrease in the rate of babies born with Down syndrome. The objective of this study was to investigate the geodemographic characteristics of women who have prenatal diagnosis in Victoria, Australia, by applying a novel consumer behaviour modelling technique in the analysis of health data. METHODS: A descriptive analysis of data on all prenatal diagnostic tests, births (1998 and 2002) and births of babies with Down syndrome (1998 to 2002) was undertaken using a Geographic Information System and socioeconomic lifestyle segmentation classifications. RESULTS: Most metropolitan women in Victoria have average or above State average levels of uptake of prenatal diagnosis. Inner city women residing in high socioeconomic lifestyle segments who have high rates of prenatal diagnosis spend 20% more on specialist physician's fees when compared to those whose rates are average. Rates of prenatal diagnosis are generally low amongst women in rural Victoria, with the lowest rates observed in farming districts. Reasons for this are likely to be a combination of lack of access to services (remoteness) and individual opportunity (lack of transportation, low levels of support and income). However, there are additional reasons for low uptake rates in farming areas that could not be explained by the behaviour modelling. These may relate to women's attitudes and choices. CONCLUSION: A lack of statewide geodemographic consistency in uptake of prenatal diagnosis implies that there is a need to target health professionals and pregnant women in specific areas to ensure there is increased equity of access to services and that all pregnant women can make informed choices that are best for them. Equally as important is appropriate health service provision for families of children with Down syndrome. Our findings show that these potential interventions are particularly relevant in rural areas. Classifying data to lifestyle segments allowed for practical comparisons of the geodemographic characteristics of women having prenatal diagnosis in Australia at a population level. This methodology may in future be a feasible and cost-effective tool for service planners and policy developers.

Prenatal diagnostic testing and Down Syndrome in Victoria 1992--2002.

OBJECTIVE: To describe patterns of uptake of prenatal diagnostic testing and prenatal detection rates for Down syndrome in Victoria with regard to maternal age and prenatal screening practices. METHODS: Analysis of routinely collected statewide datasets for 1992 to 2002, containing detailed information on all prenatal diagnoses, births and birth defects. RESULTS: Utilisation of prenatal diagnosis in women less than 37 years has increased significantly (p<0.0001), whereas in older women it has fallen from 65.1% in 1996 to 42.7% in 2002. The overall proportion of diagnostic tests prompted by an increased risk screening test result has increased five-fold over 11 years to 35.4% in 2002 (p<0.0001). Almost 6% of diagnostic tests done in 2002 detected a fetal chromosome abnormality, compared with 3.0% in 1992. Prenatal detection of Down syndrome has increased in women less than 37 years with approximately 70% of cases now diagnosed prenatally (p<0.0001). A smaller non-significant increase (from 67% to 82%) in prenatal detection of Down syndrome was observed among older women. CONCLUSIONS: The widespread use of prenatal screening for Down syndrome has changed the demographic profile of women having prenatal diagnosis in terms of their age. An increasing number and proportion of younger women and fewer older women are having prenatal diagnosis. The declining figures for diagnostic testing in older women have not had an impact on prenatal detection rates for Down syndrome. IMPLICATION: Current prenatal screening practices provide a more effective risk assessment for Down syndrome and indication for prenatal diagnosis than advanced maternal age alone.

Prevention of diabetes-induced albuminuria in transgenic rats overexpressing human aldose reductase.

Studies using pharmacologic inhibitors have implicated the enzyme aldose reductase in the pathogenesis of albuminuria and diabetic renal disease. However, a clear conclusion is not easily drawn from such studies since these pharmacologic inhibitors have nonspecific properties. To examine further the role of aldose reductase, we have overexpressed the human enzyme in a transgenic rat model. Transgene expression in the kidney was predominantly localized to the outer stripe of the outer medulla, compatible with the histotopography of the straight (S3) proximal tubule. The effect of enzyme overexpression on diabetes-induced renal function and structure was then investigated. Contrary to what may have been anticipated from the previous enzyme inhibition studies, diabetes-induced albuminuria was completely prevented by the overexpression of aldose reductase. No effect of overexpression of aldose reductase on renal structure nor on urinary excretion of beta2-microglobulin and N-acetyl-beta-D-glucosaminidase was observed in this transgenic rat model. In conclusion, our study strongly suggests that multiple roles for aldose reductase may give it a more complex place in diabetic nephropathy than is currently recognized.

Hyaluronan increases glomerular cyclooxygenase-2 protein expression in a p38 MAP-kinase-dependent process.

BACKGROUND: Accumulation of the matrix glycosaminoglycan hyaluronan occurs in many types of renal injury but could follow any provision of hyaluronan substrate to the kidney, for example, through widespread use of supplementary glucosamine in osteoarthritic conditions. Hyaluronan can increase cyclooxygenase-2 (COX-2) protein and prostaglandin production. This effect was characterized in rat renal glomeruli to determine the cellular mechanism of activation. METHODS: Isolated glomeruli were treated with purified hyaluronan (molecular mass 2 x 105 D) for up to 24 hours. RESULTS: An increase in cyclooxygenase capacity and COX-2 protein was shown to follow the activation of p38-mitogen-activated protein (MAP) kinase and to be inhibited by a specific pyridinyl imadazole inhibitor (SB 202190). Hyaluronan-induced activation of cytosolic phospholipase A2 also was shown to be a p38 MAP kinase effect in these preparations. Prostaglandin production was inhibited by COX-2-specific non-steroidal anti-inflammatory compounds (NS-398 and celecoxib) but, as shown for many non-steroidal anti-inflammatory drugs (NSAIDs), an increase in COX-2 protein accompanied this inhibition. CONCLUSIONS: We propose that these findings have clinical relevance. Prostaglandins have a number of important intrarenal regulatory effects leading to some debate over renal function with the use of NSAIDs. Where hyaluronan is increased, p38 MAP-kinase-dependent provision of prostaglandin substrate, via activation of cytosolic phospholipase A2, and a concomitant increase in cyclooxygenase-2 protein would raise renal prostaglandin levels. While NSAID treatment can prevent a rise in prostaglandin levels, it needs to be maintained to avoid possible exacerbation of pro-inflammatory conditions due to increased COX-2 protein levels.