Obstetrics and Gynaecology - Research Publications

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    Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
    Calais-Ferreira, L ; Barreto, ME ; Mendonca, E ; Dite, GS ; Hickey, M ; Ferreira, PH ; Scurrah, KJ ; Hopper, JL (OXFORD UNIV PRESS, 2022-10-13)
    BACKGROUND: In infancy, males are at higher risk of dying than females. Birthweight and gestational age are potential confounders or mediators but are also familial and correlated, posing epidemiological challenges that can be addressed by studying male-female twin pairs. METHODS: We studied 28 558 male-female twin pairs born in Brazil between 2012 and 2016, by linking their birth and death records. Using a co-twin control study matched for gestational age and familial factors, we applied logistic regression with random effects (to account for paired data) to study the association between male sex and infant death, adjusting for: birthweight, within- and between-pair effects of birthweight, birth order and gestational age, including interactions. The main outcome was infant mortality (0-365 days) stratified by neonatal (early and late) and postneonatal deaths. RESULTS: Males were 100 g heavier and more at risk of infant death than their female co-twins before [odds ratio (OR)  = 1.28, 95% confidence interval (CI): 1.11-1.49, P = 0.001] and after (OR = 1.60, 95% CI: 1.39-1.83, P <0.001) adjusting for birthweight and birth order. When adjusting for birthweight within-pair difference and mean separately, the OR attenuated to 1.40 (95% CI: 1.21-1.61, P <0.001), with evidence of familial confounding (likelihood ratio test, P <0.001). We found evidence of interaction (P = 0.001) between male sex and gestational age for early neonatal death. CONCLUSIONS: After matching for gestational age and familial factors by design and controlling for birthweight and birth order, males remain at greater risk of infant death than their female co-twins. Birthweight's role as a confounder can be partially explained by familial factors.
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    Sex Differences in Infant Mortality: A Population Data Linkage Study of Brazilian Male-Female Twin Pairs
    Calais-Ferreira, L ; Mendonça, E ; Barreto, ME ; Dite, GM ; Hickey, M ; Ferreira, PH ; Scurrah, KJ ; Hopper, JL (Swansea University, 2020-12-07)
    IntroductionEpidemiological studies of twin pairs provide researchers with the opportunity to better understand the roles of genetics and the environment on human traits and health conditions. Twin births are also of interest for public health, given they are five times more likely to be of low birth weight and preterm compared to singletons. Male twin newborns are at high risk of mortality, although the causes of such disadvantage are still largely unknown. Objectives and ApproachWe deterministically linked population birth to death records of twins born in Brazil from 2012–2016, and probabilistically linked twins within pairs through a bespoke algorithm. We studied male-female twin pairs to investigate sex differences in infant mortality stratified by early neonatal (0–6 days), late neonatal (7–27 days) and late infant (28–365 days) deaths. We used conditional logistic regression to estimate odds ratios (OR) for male sex, adjusting for birth weight and matching for familial factors by design. ResultsOur algorithm successfully matched 101,382 twin pairs, 28,558 were male-female pairs included in the study. Average birthweight was 100g greater for males compared with females. We found that males were at higher risk of infant mortality than their female co-twins even after adjusting for birth weight and familial factors (aOR = 1.42, 95% CI: 1.22–1.66). The aORs for neonatal death increased from those born at less than 28 weeks to those born at 28–31, 32–26 and 37+ weeks: 1.47 (1.02–2.13), 1.73 (1.17–2.57), 1.99 (1.17–3.38), and 3.35 (1.29–8.73), respectively. Conclusion / ImplicationsMale twins have greater risk of infant and neonatal mortality compared with female co-twins, more so the higher the gestational age. Unmeasured familial and maternal factors may influence the role of birth weight in the association between sex and poor early life outcomes.
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    Motivators of Inappropriate Ovarian Cancer Screening: A Survey of Women and Their Clinicians
    Macdonald, C ; Mazza, D ; Hickey, M ; Hunter, M ; Keogh, LA ; Jones, SC ; Saunders, C ; Nesci, S ; Milne, RL ; Mclachlan, S-A ; Hopper, JL ; Friedlander, ML ; Emery, J ; Phillips, K-A (OXFORD UNIV PRESS, 2021-02)
    BACKGROUND: This study examined why women and doctors screen for ovarian cancer (OC) contrary to guidelines. METHODS: Surveys, based on the Theoretical Domains Framework, were sent to women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer and family physicians and gynecologists who organized their screening. RESULTS: Of 1264 Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer women, 832 (65.8%) responded. In the past 2 years, 126 (15.1%) had screened. Most of these (n = 101, 80.2%) would continue even if their doctor told them it is ineffective. For women, key OC screening motivators operated in the domains of social role and goals (staying healthy for family, 93.9%), emotion and reinforcement (peace of mind, 93.1%), and beliefs about capabilities (tests are easy to have, 91.9%). Of 531 clinicians 252 (47.5%) responded; a minority (family physicians 45.8%, gynecologists 16.7%) thought OC screening was useful. For gynecologists, the main motivators of OC screening operated in the domains of environmental context (lack of other screening options, 27.6%), and emotion (patient peace of mind, 17.2%; difficulty discontinuing screening, 13.8%). For family physicians,, the strongest motivators were in the domains of social influence (women ask for these tests, 20.7%), goals (a chance these tests will detect cancer early, 16.4%), emotion (patient peace of mind, 13.8%), and environmental context (no other OC screening options, 11.2%). CONCLUSION: Reasons for OC screening are mostly patient driven. Clinician knowledge and practice are discordant. Motivators of OC screening encompass several domains, which could be targeted in interventions to reduce inappropriate OC screening.
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    The cognitive, affective, social and environmental drivers of inappropriate ovarian cancer screening: A survey of women and their clinicians using the theoretical domains framework
    Macdonald, C ; Mazza, D ; Hickey, M ; Hunter, M ; Keogh, LA ; Jones, SC ; Saunders, C ; Nesci, S ; Milne, RL ; McLachlan, SA ; Hopper, J ; Friedlander, M ; Emery, J ; Phillips, KA (ELSEVIER, 2020-09)
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    Improved quality of risk-reducing salpingo-oophorectomy in Australasian women at high risk of pelvic serous cancer
    Lee, YC ; Bressel, M ; Grant, P ; Russell, P ; Smith, C ; Picken, S ; Camm, S ; Kiely, BE ; Milne, RL ; McLachlan, SA ; Hickey, M ; Friedlander, ML ; Hopper, JL ; Phillips, KA (SPRINGER, 2017-10)
    OBJECTIVES: The quality of risk-reducing salpingo-oophorectomy (RRSO) performed in Australasian women was previously reported to be suboptimal. Here we describe the quality of RRSO performed since 2008 in women enrolled in the same cohort and determine whether it has improved. DESIGN: Prospective cohort study of women at high risk of pelvic serous cancer (PSC) in kConFab. Eligible women had RRSO between 2008 and 2014 and their RRSO surgical and pathology reports were reviewed. "Adequate" surgery and pathology were defined as complete removal and paraffin embedding of all ovarian and extra-uterine fallopian tube tissue, respectively. Associations between clinical factors and "adequate" pathology were assessed using logistic regression. Data were compared with published cohort data on RRSO performed prior to 2008 using Chi square test. RESULTS: Of 164 contemporary RRSOs performed in 78 centres, 158/159 (99%) had "adequate" surgery and 108/164 (66%) had "adequate" pathology. Surgery performed by a gynaecologic oncologist rather than a general gynaecologist [OR 8.2, 95%CI (3.6-20.4), p < 0.001], surgery without concurrent hysterectomy [OR 2.5, 95%CI (1.1-6.0), p = 0.03], more recent year of surgery [OR 1.4, 95%CI (1.1-1.8), p = 0.02], and clinical notation that indicated high risk [OR 19.4, 95%CI (3.1-385), p = 0.008] were independently associated with "adequate" pathology. Both surgery and pathology were significantly more likely to be "adequate" (p < 0.001) in this contemporary sample. CONCLUSION: The quality of RRSOs has significantly improved since our last report. Surgery by a gynaecologic oncologist who informs the pathologist that the woman is at high risk for PSC is associated with optimal RRSO pathology.
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    Meanings of abortion in context: accounts of abortion in the lives of women diagnosed with breast cancer
    Kirkman, M ; Apicella, C ; Graham, J ; Hickey, M ; Hopper, JL ; Keogh, L ; Winship, I ; Fisher, J (BMC, 2017-04-05)
    BACKGROUND: A breast cancer diagnosis and an abortion can each be pivotal moments in a woman's life. Research on abortion and breast cancer deals predominantly with women diagnosed during pregnancy who might be advised to have an abortion. The other-discredited but persistent-association is that abortions cause breast cancer. The aim here was to understand some of the ways in which women themselves might experience the convergence of abortion and breast cancer. METHODS: Among 50 women recruited from the Australian Breast Cancer Family Study and interviewed in depth about what it meant to have a breast cancer diagnosis before the age of 41, five spontaneously told of having or contemplating an abortion. The transcripts of these five women were analysed to identify what abortion meant in the context of breast cancer, studying each woman's account as an individual "case" and interpreting it within narrative theory. RESULTS: It was evident that each woman understood abortion as playing a different role in her life. One reported an abortion that she did not link to her cancer, the second was relieved not to have to abort a mid-treatment pregnancy, the third represented abortion as saving her life by making her cancer identifiable, the fourth grieved an abortion that had enabled her to begin chemotherapy, and the fifth believed that her cancer was caused by an earlier abortion. CONCLUSIONS: The women's accounts illustrate the different meanings of abortion in women's lives, with concomitant need for diverse support, advice, and information.
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    Anti-Mullerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations
    Phillips, K-A ; Collins, IM ; Milne, RL ; McLachlan, SA ; Friedlander, M ; Hickey, M ; Stern, C ; Hopper, JL ; Fisher, R ; Kannemeyer, G ; Picken, S ; Smith, CD ; Kelsey, TW ; Anderson, RA (OXFORD UNIV PRESS, 2016-05)
    STUDY QUESTION: Do women with ITALIC! BRCA1 or ITALIC! BRCA2 mutations have reduced ovarian reserve, as measured by circulating anti-Müllerian hormone (AMH) concentration? SUMMARY ANSWER: Women with a germline mutation in ITALIC! BRCA1 have reduced ovarian reserve as measured by AMH. WHAT IS KNOWN ALREADY: The DNA repair enzymes encoded by ITALIC! BRCA1 and ITALIC! BRCA2 are implicated in reproductive aging. Circulating AMH is a biomarker of ovarian reserve and hence reproductive lifespan. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of AMH concentrations of 693 women at the time of enrolment into the Kathleen Cuningham Foundation Consortium for research in the Familial Breast Cancer (kConFab) cohort study (recruitment from 19 August 1997 until 18 September 2012). AMH was measured on stored plasma samples between November 2014 and January 2015 using an electrochemiluminescence immunoassay platform. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible women were from families segregating ITALIC! BRCA1 or ITALIC! BRCA2 mutations and had known mutation status. Participants were aged 25-45 years, had no personal history of cancer, retained both ovaries and were not pregnant or breastfeeding at the time of plasma storage. Circulating AMH was measured for 172 carriers and 216 non-carriers from families carrying ITALIC! BRCA1 mutations, and 147 carriers and 158 non-carriers from families carrying ITALIC! BRCA2 mutations. Associations between plasma AMH concentration and carrier status were tested by linear regression, adjusted for age at plasma storage, oral contraceptive use, body mass index and cigarette smoking. MAIN RESULTS AND THE ROLE OF CHANCE: Mean AMH concentration was negatively associated with age ( ITALIC! P < 0.001). Mutation carriers were younger at blood draw than non-carriers ( ITALIC! P ≤ 0.031). ITALIC! BRCA1 mutation carriers had, on average, 25% (95% CI: 5%-41%, ITALIC! P = 0.02) lower AMH concentrations than non-carriers and were more likely to have AMH concentrations in the lowest quartile for age (OR 1.84, 95% CI: 1.11-303, ITALIC! P = 0.02). There was no evidence of an association between AMH concentration and ITALIC! BRCA2 mutation status ( ITALIC! P = 0.94). LIMITATIONS, REASONS FOR CAUTION: AMH does not directly measure the primordial follicle pool. The clinical implications of the lower AMH concentrations seen in ITALIC! BRCA1 mutation carriers cannot be assessed by this study design. WIDER IMPLICATIONS OF THE FINDINGS: Women with a germline mutation in ITALIC! BRCA1 may have reduced ovarian reserve. This is consistent with other smaller studies in the literature and has potential implications for fertility and reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: kConFab is supported by a grant from the Australian National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. K.A.P. is an Australian National Breast Cancer Foundation Practitioner Fellow. J.L.H. is a NHMRC Senior Principal Research Fellow. M.H. is a NHMRC Practitioner Fellow. R.A.A. reports personal fees from Roche Diagnostics & Beckman Coulter outside the submitted work and C.S. reports other earnings from Melbourne IVF outside the submitted work. The remaining authors have nothing to declare and no conflicts of interest.