Pre-eclampsia and assisted reproductive technologies: consequences of advanced maternal age, interbirth intervals, new partner and smoking habits

Objective: To examine the risk of pre-eclampsia (PE) in women conceiving after assisted reproductive technologies (ART). Potential confounding from maternal age, long intervals between births, new partner and smoking were evaluated.

Design and setting: Population-based cohort study with data from the Medical Birth Registry of Norway.

Population: A total of 501,766 mothers with offspring from 1988 to 2009.

Methods: Births to the same mother were linked in sibship data files with information of ART.

Main outcome measures: Odds ratio (OR) (95% confidence intervals) of PE in pregnancies conceived by ART compared with spontaneous conception, stratified by parity.

Results: The prevalence of PE was 5.1% in first, 2.2% in second and 2.1% in third pregnancies. Corresponding figures in ART pregnancies were 6.0%, 3.3% and 4.4%. Hence, the odds ratios of PE in ART pregnancies relative to spontaneous pregnancies increased from 1.2 (1.1-1.3) in first, 1.5 (1.3-1.8) in second to 2.1 (1.4-3.3) in third pregnancies. Adjusting by maternal age lowered the odds ratio to 1.3 (1.1-1.6) and 1.8 (1.2-2.8) in second and third pregnancies, respectively. Multi-adjusted, birth interval had more impact than change of partner. Smoking was associated with a strongly reduced PE risk (odds ratio 0.65; 0.62-0.69), but there was no confounding by smoking on the ART associated risk.

Conclusions: Assisted reproductive technologies increases the risk of PE, and the risk may increase by parity. The association between ART pregnancies and PE is to some extent explained by interbirth intervals and advanced maternal age, but not to change of partner or smoking.