Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders.

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A 'pathway' driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the 'gene-environment neuroscience interaction'. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench-to-bedside scientific discovery agenda with ongoing clinician and patient engagement. WHAT THIS PAPER ADDS: Precision medicine has predominantly focused on genetic risk factors. The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied. A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented. The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.

Inequality in out of pocket fees, government funding and utilisation of maternal health services in Australia.

This study aimed to assess the distribution of service utilisation, out-of-pocket fees and government funding for maternal health care in Australia by socioeconomic group. A large linked administrative dataset was utilised. Women were grouped into socioeconomic quintiles using an area-based measure of socioeconomic status. Descriptive statistics were used to quantify the distribution of number of services, out of pocket fees, and government funding by socioeconomic quintile. Needs-adjusted concentration indices (CINA) were utilised to quantify inequity. The mean out of pocket fees for women of least socioeconomic advantage was $1,026 and for women of most socioeconomic advantage the mean was $2,432 (CINA 0.093, 95% CI: 0.088 - 0.098). However, use of many services were higher for women of most socioeconomic advantage: private obstetrician (CINA: 0.035, 95% CI: 0.032 - 0.038), other specialist services (CINA: 0.089, 95%CI: 0.083 - 0.094), and diagnostic and pathology tests (CINA: 0.027, 95%CI: 0.025 - 0.030). Federal government funding through Medicare was distributed towards women of most socioeconomic advantage (CINA: 0.036, 95%CI: 0.033 - 0.039); whereas government public hospital funding was skewed towards women of least socioeconomic advantage (CINA: -0.05, 95%CI: -0.057 - -0.046). Future policy changes in Australia's healthcare system need to ensure that women of least socioeconomic advantage have adequate access to maternity and early childhood care, and out of pocket fees are not an access barrier.

Breastfeeding patterns and effects of minimal supplementation on breastfeeding exclusivity and duration in term infants: A prospective sub-study of a randomised controlled trial.

AIM: Despite international recommendations, less than one-third of Australian women exclusively breastfeed for 6 months. The aims of this study were to prospectively determine rates and factors associated with the type and duration of breastfeeding in the first year and examine the effect of minimal supplementation. METHODS: We conducted a sub-study of a randomised controlled trial in Sydney, Australia, which included 635 women with uncomplicated term births who intended to breastfeed. Data were collected daily for 56 days, and then at 2, 6 and 12 months post-partum. RESULTS: Breastfeeding outcomes were evaluated for 553 (87%), 480 (76%) and 392 (62%) women at 2, 6 and 12 months. Exclusive breastfeeding was 81% at 2 months and 8% at 6 months. Partial breastfeeding was 75% at 6 months and 54% at 12 months. Factors associated with breastfeeding cessation included caesarean birth, low milk supply, problems latching, increased time to breastfeed, use of formula >7 days in the first 2 months, return to work and early introduction of solids. Breast pain in the first week was associated with a 10% decrease in exclusive breastfeeding. Cracked nipples and no previous breastfeeding experience were associated with supplementation of ≤7 days but had no effect on long-term breastfeeding duration. CONCLUSIONS: Exclusive breastfeeding declined significantly between 2 and 6 months post-partum. Early intervention and education to prolong breastfeeding duration should include strategies to manage breast pain and nipple damage to minimise prolonged supplementation. Consistent guidelines about introduction of complementary foods, improved maternity leave and workplace incentives could be effective in prolonging breastfeeding.

Financing Maternity and Early Childhood Healthcare in The Australian Healthcare System: Costs to Funders in Private and Public Hospitals Over the First 1000 Days.

BACKGROUND: Maternity care is a significant contributor to overall healthcare expenditure, and private care is seen as a mechanism to reduce the cost to public funders. However, public funders may still contribute to part of the cost of private care. The paper aims to quantify (1) the cost to different funders of maternal and early childhood healthcare over the first 1000 days for both women giving birth in private and public hospitals; (2) any variation in cost to different funders by birth type; and (3) the cost of excess caesarean sections in public and private hospitals in Australia. METHODS: This study utilised a whole of population linked administrative dataset, and classified costs by the funding source. The mean cost to different funders for private hospital births, and public hospital births in the Australian state, Queensland are presented by time period and by birth type. The World Health Organization's (WHO's) C-model was used to identify the optimal caesarean section rate based upon demographic and clinical factors, and counterfactual analysis was utilised to identify the cost to different funders if caesarean section had been utilised at this rate across Australia. RESULTS: We found that for women who gave birth in a public hospital as a public patient, the mean cost was $22 474. For women who gave birth in a private hospital the mean cost was $24 731, and the largest contributor was private health insurers ($11 550), followed by Medicare ($7261) and individuals ($3312). Private hospital births cost government funders $10 050 on average; whereas public hospital public patient births cost government funders $21 723 on average and public hospital private patient births cost government funders $20 899 on average. If caesarean section deliveries were reduced, public hospital funders could save $974 million and private health insurers could save $216 million. CONCLUSION: Private hospital births cost government funders less than public hospital births, but government funders still pay for around 40% of the cost of private hospital births. Caesarean sections, which are more frequently performed in private hospitals, are costly to all funders and reducing them could impart significant cost savings to all funders.

Knowledge, advice and attitudes toward women driving a car after caesarean section or hysterectomy: A survey of obstetrician/gynaecologists and midwives.

BACKGROUND: Women are given variable information about when to recommence driving after surgery. AIMS: To assess obstetrician/gynaecologists' and midwives' knowledge, attitudes and advice about car driving after abdominal surgery including hysterectomy or caesarean section (CS). MATERIALS AND METHODS: An anonymous SurveyMonkey™ survey was distributed to accredited trainees and Fellows of the Royal Australian New Zealand College of Obstetricians and Gynaecologists and midwives registered with the Australian College of Midwives by email in November 2013. Demographic information, recommendations about driving, and reasoning behind these recommendations were collected. RESULTS: Nine hundred and seventy-seven clinician responses (15.8%) were analysed: 555 midwives, 92 trainees and 330 Fellows. Ninety-six percent gave advice about driving after surgery. Respondents considered pain (85.6%), medication (73.2%) and mobility (70.5%) the most important factors when advising on resumption of driving. After uncomplicated CS, 19% said they would advise a well woman that she could drive <4 weeks, 18% advised four weeks, 33% advised five to six weeks and 27% did not give a specific timeframe. Similar timeframes were given following hysterectomy. Of each professional group, trainees (49%) and midwives (48%) were more likely to advise waiting five to six weeks to resume driving compared with Fellows (9%) (P < 0.001). Although 71.5% of respondents thought that most women drove before four weeks, only 33.9% of respondents thought driving earlier than advice given was unsafe. CONCLUSIONS: Clinicians frequently give advice about driving after surgery. This advice is inconsistent and many advise women not to drive for significant time periods. This study highlights the need for education and research about driving after surgery.

Iron supplement use in pregnancy - Are the right women taking the right amount?

OBJECTIVES: To examine the prevalence and determinants of iron supplement use and the amount of iron consumed from iron-containing supplements. METHODS: A cross-sectional survey was performed in antenatal clinics in two tertiary hospitals in Sydney, Australia between January and March 2014. RESULTS: Of 612 (91% response rate) pregnant women, 589 with complete data were analysed. Overall iron-containing supplement use was 88.0%, of which 70.1% was multivitamin (MV) only, 7.2% was iron-only and 22.2% was both. Use of iron-containing supplements was associated with increased gestational age, a diagnosis of anaemia or iron deficiency (ID) in the current pregnancy and pre-pregnancy use of an iron-containing supplement. Several risk factors for ID or anaemia such as non-red meat eating and previous miscarriage were not associated with current iron supplement use. About 65% of women diagnosed with ID, and 62.3% of women diagnosed with anaemia were taking an iron-only supplement, with or without a MV. The proportion of women consuming low (<30), preventative (30-99) and treatment (≥100) mg/day doses were 36.8%, 45.4%, and 17.8%, respectively. Only 46.7% of women diagnosed with ID were taking ≥100 mg/day iron from supplements, while 23.3% were taking <30 mg/day. CONCLUSION: Women are consuming varying doses of iron and some high-risk women are taking inadequate doses of iron to prevent or treat ID or iron deficiency anaemia. Healthcare professionals are best positioned to advise women on iron supplement use in pregnancy and should educate women individually about the type and dose of supplement best suited to their needs.

Systematic review of the impact of sacral neuromodulation on clinical symptoms and gastrointestinal physiology.

BACKGROUND: Sacral neuromodulation (SNM) has emerged as a treatment option for faecal incontinence (FI). However, its objective effect on symptoms and anorectal function is inconsistently described. This study aimed to systematically review the impact of SNM on clinical symptoms and gastrointestinal physiology in patients with FI, including factors that may predict treatment outcome. METHODS: An electronic search of MEDLINE (1946-2014)/EMBASE database was performed in accordance with PRISMA guidelines. Articles that reported the relevant outcome measures following SNM were included. Clinical outcomes evaluated included: frequency of FI episodes, FI severity score and success rates. Its impact on anorectal and gastrointestinal physiology was also evaluated. RESULTS: Of 554 citations identified, data were extracted from 81 eligible studies. Meta-analysis of the data was precluded due to lack of a comparison group in most studies. After permanent SNM, 'perfect' continence was noted in 13-88% of patients. Most studies reported a reduction in weekly FI episodes (median difference of the mean -7.0 (range: -24.8 to -2.7)) and Wexner scores (median difference of the mean -9 (-14.9 to -6)). A trend towards improved resting and squeeze anal pressures and a reduction in rectal sensory volumes were noted. Studies failed to identify any consistent impact on other physiological parameters or clinicophysiological factors associated with success. CONCLUSION: SNM improves clinical symptoms and reduces number of incontinence episodes and severity scores in patients with FI, in part by improving anorectal physiological function. However, intervention studies with standardized outcome measures and physiological techniques are required to robustly assess the physiological impact of SNM.

Dietary vitamin, mineral and herbal supplement use: a cross-sectional survey of before and during pregnancy use in Sydney, Australia.

AIM: To describe the use of dietary vitamin, mineral and herbal supplements before and during pregnancy. MATERIALS AND METHODS: Pregnant women attending for antenatal care at two tertiary Sydney hospitals between January and March 2014 completed an anonymous survey. Information on general maternal and pregnancy characteristics and the use of dietary and herbal supplements, including type, duration and sources of information, was collected. Frequency and contingency tabulations were performed. RESULTS: A total of 612 women agreed to participate (91% response rate). Of 589 women included in the analysis, mean gestational age at the time of survey was 28.5 weeks (SD 8.3), 55% had no children, and 67% were tertiary-educated. Overall, 62.9% of women reported taking a multivitamin (MV) and/or folic acid (FA) supplement in the 3 months prepregnancy, and 97.5% took a MV and/or FA in the first trimester. At the time of the survey, 93.8% of women were taking at least one supplement (median 2, range 1-13). During pregnancy, 79.1% of women were taking MVs, including 59.2% taking MV only and 19.9% taking MV and FA. The five most common supplements outside of a MV were FA (31%), iron (30%), vitamin D (23%), calcium (13%) and fish oil (12%). Reported herbal supplement rates were low. CONCLUSION: Folic acid, MVs and other supplements use during and prepregnancy is relatively high, although prepregnancy FA supplementation rates could still be improved. Further research on the actual dosages and dietary intakes consumed is needed to examine whether pregnant women have adequate intake of nutrients, regardless of supplement use.

Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study.

OBJECTIVE: The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia). DESIGN: Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6 years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared. RESULTS: Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40 weeks. CONCLUSION: The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the decline.

Development and pilot-testing of a decision aid for women with a breech-presenting baby.

OBJECTIVE: To develop a decision aid for pregnant women with a breech presentation at term, and to assess its acceptability. METHODS: The external cephalic version (ECV) decision aid was developed using the Ottawa Decision Support Framework and a systematic review of the evidence to provide probabilistic information about the benefits and risks of options. It incorporates a workbook supplemented by a CD and worksheet, and these were evaluated in a pilot study using self-administered questionnaires. PARTICIPANTS: 19 women with a breech presentation attending antenatal clinics at a local obstetric hospital and 11 recently pregnant women. FINDINGS: Of 30 women surveyed, nearly all found the decision aid clear and easy to understand, and thought that enough information was provided for them to make a decision. Women experienced increased knowledge, reduced decisional conflict, increased satisfaction and participation in decision making without increased anxiety. Participants also found the tool helpful and would recommend it to others. KEY CONCLUSIONS: The ECV decision aid was well accepted and helpful for pregnant women with a breech presenting baby. We are currently evaluating the decision aid in a randomised trial to assess cognitive, affective and health outcomes.