1 maternal shift work and the risk of urogenital defects in offspring conceived using infertility...
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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