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Maternal Shift Work and the Risk of Urogenital Defects in Offspring Conceived Using Infertility Treatment

Fertility Society Australia Conference 2015, Canberra

Renae C. Fernandez1-3, Kristyn J. Willson2,3, Vivienne M. Moore2,3, Michael J. Davies1,3

 1School of Medicine, 2School of Public Health, 3Robinson Research Institute, University of Adelaide

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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

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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).

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• 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

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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.

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ResultsParameters OR

Lower CI

UpperCI

 Parameters OR

LowerCI

UpperCI

Exposed to Light at night   Infertility diagnosis (cont.)      No† 1.00 - -   Ovulatory 0.73 0.27 2.00Yes 1.66 1.05 2.62   Tubal 0.98 0.52 1.85Baby sex   Endometriosis 1.28 0.66 2.48Female† 1.00 - -   Other/mixed 0.76 0.28 2.08Male 3.94 2.63 5.90   Combined male/female 0.86 0.51 1.46Multiplicity         Idiopathic 0.92 0.45 1.55Singleton† 1.00 - -   ART treatment type      Multiple 1.13 0.78 1.63   Spontaneous 0.86 0.30 2.45Maternal age   Minimal or OI Only 1.00 0.55 1.83< 25 0.90 0.33 2.48   IUI 1.33 0.71 2.4925-29† 1.00 - -   IVF Fresh† 1.00 - -30-34 0.87 0.58 1.30   IVF Frozen 0.85 0.42 1.7335-39 0.76 0.45 1.15   ICSI Fresh 2.11 1.23 3.62≥ 40 0.59 0.23 1.49   ICSI Frozen 1.02 0.39 2.71Infertility diagnosis         GIFT 1.38 0.73 2.61Male infertility† 1.00 - -   Donor oocyte 1.30 0.40 4.25

† Reference category

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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

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Co-Authors: Wilson KJ, Moore VM, Davies MJ.

Acknowledgements: Life Course and Intergenerational Health Research Group