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Children with birth defects who were conceived via in vitro fertilization (IVF) were more likely to develop childhood cancer compared to those conceived naturally, according to the results of a cohort study.

Kids with a major birth defect conceived via IVF had nearly seven times the risk of cancer than those without a birth defect (hazard ratio 6.90, 95% CI 3.73-12.74), reported Barbara Luke, ScD, MPH, of Michigan State University in East Lansing.

Children who had a birth defect and were conceived without medical assistance, however, were three times more likely to develop cancer (HR 3.15, 95% CI 2.40-4.14), researchers wrote in .

Luke's group proposed that the epigenetic alterations -- changes in the chemical structure of the DNA that do not change the coding sequence -- that occur when an embryo is grown in a lab result in reprogramming that may cause birth defects and cancer in this population.

"IVF-conceived children are at about one-third greater risk of birth defects compared to their naturally-conceived counterparts, as well as at higher risk of childhood cancer, although in absolute terms these numbers are small," Luke told 名媛直播.

"An unresolved question in assisted reproduction research remains the contribution of parental versus treatment factors to adverse outcomes," Luke said. She added that most likely it's a combination of both, and further research is still warranted.

Alan Penzias, MD, a reproductive endocrinologist at Boston IVF, who was not involved in the study, commented that while continued research into causes and prevention of cancer should remain a priority, the absolute risk of cancer in IVF babies is small.

"Fortunately, the overwhelming majority of children born as a result of in vitro fertilization are healthy," Penzias said in an email. "The positive impact on families who would otherwise not exist without fertility treatment is immeasurable."

Penzias recognized that epigenetic alterations as a result of IVF treatment could be a potential mechanism for birth defects and cancer. However, he also noted that the parental age of study participants who conceived via IVF was higher than those who conceived naturally, and it is also known that people accumulate epigenetic modifications as they age.

"I think these studies need to move to look for molecular clues," said Logan Spector, PhD, professor of pediatrics at the University of Minnesota in Minneapolis and faculty in the Masonic Cancer Center, who also was not involved with the study.

Spector, who has previously studied the association between IVF and cancer, said there may be molecular differences in tumors between kids born from IVF and those conceived without medical assistance.

Previous research has shown an increased risk of childhood cancer with some IVF treatments. Birth defects have also been linked to cancer risk; however, the association has never been investigated in children conceived via IVF.

Luke and colleagues linked birth certificate data from four states (Massachusetts, New York, Texas, and North Carolina) to birth defects registries, cancer registries, the national IVF database, and the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System (SART CORS). They included births from 2004 to 2016.

All births were grouped into categories of fertile and IVF. Children were stratified according to the number of birth defects they had.

Exclusion criteria included gestational age of less than 22 weeks or birth weight of less than 300 g. In the IVF cohort, only births conceived with autologous oocytes and fresh embryos were included, as those conditions most closely paralleled natural conception.

More than one million children were born to mothers who were fertile, and around 53,000 conceived via IVF. Approximately 1.8% of children in the fertile group were born with a birth defect, compared to 2.4% in the IVF group. Most parents who conceived a child without medical assistance were between 18 and 34 years old, while the majority who used IVF were 35 and older.

Cancer risk was higher in children with birth defects in both the fertile and IVF groups. The hazard ratio of cancer for children with a nonchromosomal defect was 2.07 (95% CI 1.47-2.91) among those in the fertile group, and 4.04 (95% CI 1.86-8.77) in the IVF group.

Among babies with a chromosomal defect, the hazard ratio of cancer was 15.45 (95% CI 10.00-23.86) in children conceived without medical assistance, and 38.91 (95% CI 15.56-97.33) in the IVF group.

Luke and colleagues were not able to assess specific birth defect-cancer combination risks. They also acknowledged that the average follow-up period was around 6 years. when the incidence of childhood cancer is at its lowest.

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