1. 1 Maternal Shift Work and the Risk of Urogenital Defects in Offspring Conceived Using Infertility Treatment Fertility Society Australia Conference 2015, Canberra Renae C. Fernandez 1-3, Kristyn J. Willson 2,3, Vivienne M. Moore 2,3, Michael J. Davies 1,3 1 School of Medicine, 2 School of Public Health, 3 Robinson Research Institute, University of Adelaide

2. 2 Background Exposure to light at night is known to interfere with circadian rhythms Altered oestrogen & melatonin levels are observed among female shift workers (Ji et al. 2012, Gomez- Acebo et al. 2015) Melatonin plays an important role in placental function Risk factors for urogenital defects –Androgen/oestrogen balance in utero (male babies), placental insufficiency, assisted conception (van der Zanden 2014) Urogenital defects Exposure to light at night Altered endocrinology

3. 3 Aim To investigate the risk of urogenital birth defects among children born to female shift workers in a South Australian (SA) birth cohort conceived using assisted reproductive technologies (ART).

4. 4 Linked dataset –patient data from all ART clinics (1986-2002), SA Birth Defects Register, SA Perinatal Statistics Collection. Outcome variable –Urogenital birth defects detected up to the child’s fifth birthday. Exposure variable –Shift work-related exposure to light at night inferred using a job-exposure matrix. Analysis –Bayesian data augmentation to counteract sparse data –Logistic regression using Generalised Estimating Equations –A series of models was specified, progressively considering potential covariates –Final results adjusted for maternal age, infertility diagnosis, treatment type, multiplicity, baby sex. Methods

5. 5 Summary of Results Urogenital birth defects occurred in 23.4 per 1,000 ART births. 11% of total ART births (n=6,315) were to mothers exposed to shift work. Risk of urogenital birth defects was significantly higher among births to female shift workers exposed to light at night, OR=1.68 (95% CI 1.06-2.62). Male babies and babies conceived using fresh ICSI treatment also had significantly higher risk. The risk of urogenital defects did not significantly vary across infertility diagnoses after adjusting for other factors.

6. 6 Results ParametersOR Lower CI Upper CI ParametersOR Lower CI Upper CI Exposed to Light at night Infertility diagnosis (cont.) No † 1.00-- Ovulatory 0.730.272.00 Yes 1.661.052.62 Tubal 0.980.521.85 Baby sex Endometriosis 1.280.662.48 Female † 1.00-- Other/mixed 0.760.282.08 Male 3.942.635.90 Combined male/female 0.860.511.46 Multiplicity Idiopathic 0.920.451.55 Singleton † 1.00-- ART treatment type Multiple 1.130.781.63 Spontaneous 0.860.302.45 Maternal age Minimal or OI Only 1.000.551.83 < 25 0.900.332.48 IUI 1.330.712.49 25-29 † 1.00-- IVF Fresh † 1.00-- 30-34 0.870.581.30 IVF Frozen 0.850.421.73 35-39 0.760.451.15 ICSI Fresh 2.111.233.62 ≥ 40 0.590.231.49 ICSI Frozen 1.020.392.71 Infertility diagnosis GIFT 1.380.732.61 Male infertility † 1.00-- Donor oocyte 1.300.404.25 † Reference category

7. 7 Discussion & Future Work Potential mechanisms –Hormone disturbances and development in utero –Melatonin and impaired placental function Strengths –Cohort size and completeness of outcome data Limitations –Crude exposure assessment Next steps –Repeat analysis using first pregnancies only (strengthen exposure classification) –Repeat analysis in general population cohort –Role of infertility and/or ART treatment type as mediators

8. 8 Co-Authors: Wilson KJ, Moore VM, Davies MJ. Acknowledgements: Life Course and Intergenerational Health Research Group