Cerebral Palsy Risk Among IVF Children Continues to Decline

Anne Laerke Spangmose, MD

Findings of a large-scale population study demonstrate the risk of cerebral palsy in in vitro fertilization (IVF) children has declined by more than 50% over the past 2 decades.

Anne Laerke Spangmose, MD, and a team of Europe-based investigators used data from birth cohorts in Denmark, Finland, and Sweden to learn if the risk of cerebral palsy changed over a 20-year period in children born after assisted reproductive technology. The colleagues said the results were likely due to the reduction in the rate of twin births in IVF.

The results provided strong evidence that reducing the number of twins born after IVF treatment has lowered cerebral palsy risk, Spangmose, from Rigshospitalet, Copenhagen University Hospital, said.

“Multiple embryo transfer is still standard care in many countries,” she said in a statement. “Our findings emphasize that single embryo transfer and singleton births should be encouraged worldwide.”

Spangmose and the team collected data from Denmark (birth years 1994-2010) and Finland (1990-2010) including 2 cohorts: 55,233 assisted reproductive technology children and 2,327,350 spontaneously conceived children. Of the assisted reproductive technology children, 37,404 were singletons, 17,057 were twins, and 772 were higher-order multiples.

The investigators assessed the risk of cerebral palsy by stratifying the births into groups: those born 1990-1994, 1995-1999, 2000-2004, and 2005-2010. The children were followed up until 2014.

Cerebral palsy was defined as G80 ICD-10 diagnoses registered in the patient registry before the age of 10 years old. The team used logistic regression models to compare cerebral palsy for assisted reproductive technology children and spontaneously conceived children, singletons, and twins.

Overall, there were 307 (.6%) of assisted reproductive technology children and 5911 (.3%) of spontaneously conceived children diagnosed with cerebral palsy. The crude risk of cerebral palsy in assisted reproductive technology children decreased consistently from .9% from 1990-1994 to .4% from 2005-2010. There was a decrease in risk for assisted reproductive technology singletons from .7% from 1990-1994 to .3% from 2005-2010, while risk stayed stable for assisted reproductive technology twins (.7%), spontaneously conceived singletons (.2%) and spontaneously conceived twins (.8%). The risk remained unchanged for spontaneously conceived children (.3%).

The adjusted risk of cerebral palsy was higher for IVF children compared to spontaneously conceived children (adjusted odds ratio (aOR, 1.93; 95% CI, 1.71-2.17). Risk stayed increased after adjustment for plurality (aOR, 1.18; 95% CI, 1.04-1.34). There was a higher risk of cerebral palsy for IVF singletons (aOR, 1.32; 95% CI, 1.1-1.57).

Over time, the team saw a consistent decrease in cerebral palsy risk for IVF versus spontaneously conceived children (1990-1994: aOR, 2.88; [95% CI, 1.81-4.32]; 2005-2010: aOR, 1.34; [95% CI, 1.12-1.61]). The risk of cerebral palsy was no longer statistically significant from 2005-2010 after further adjustments for plurality (aOR, .96; 95% CI, .79-1.15). Cerebral palsy risk decreased substantially over time for assisted reproductive technology singletons compared with spontaneously conceived singletons (1990-1994; aOR, 2.53; [95% CI, 1.2-4.63]; 2005-2010; aOR, 1.21 [95% CI, .88-1.62]).

The findings suggested limiting the number of twins born after IVF treatment lowers the risk of cerebral palsy among the assisted reproductive technology population. Single embryo transfer should be encouraged worldwide, the investigators concluded.

The study, “The risk of cerebral palsy in ART children has more than halved over two decades—a Nordic collaborative study on 55,233 liveborn children,” was presented as part of the online Annual Meeting the European Society of Human Reproduction and Embryology.