IVF Associated With Increased Risk for Childhood Cancer

From Medscape Medical News
IVF Associated With Increased Risk for Childhood Cancer

Nick Mulcahy

July 20, 2010 — Children born after in vitro fertilization (IVF) are at a "moderately" increased risk of developing childhood cancer, according to a population-based study from Sweden published online July 19 in Pediatrics.

The study, which is the largest to date, is the first to show that the increased risk is statistically significant.

The researchers compared 26,692 children born after IVF with a control group of 2.4 million children not conceived by IVF between 1982 and 2005.

They identified 53 cases of cancer in children who were born after IVF (38 cases were expected). The total cancer risk estimate was 1.42 (95% confidence interval [CI], 1.09 - 1.87; P = .01).

"It should be stressed that the individual risk for a child who is born after IVF to develop childhood cancer is low," write the authors, led by Bengt Källén, MD, PhD, from the Tornblad Institute of the University of Lund in Sweden.

Dr. Källén and colleagues do not believe that IVF itself is the likely cause of the risk.

"This is probably not attributable to the IVF procedure itself but could be an effect of confounding from unidentified characteristics of women who undergo IVF or could act via the widely known increased risks for neonatal complication," they write.

The increased risk for perinatal complications from IVF births includes congenital malformations, the authors point out.

The study is actually an outgrowth of a previous study by the same Swedish researchers. In the earlier study (Fertil Steril. 2005;84:605-610), there were fewer children born after IVF and less follow-up time. That study found nearly the same risk estimate (1.41), but the result was not statistically significant (95% CI, 0.98 - 2.03).

Statistics Include Langerhans Cell Histiocytosis

Among the 53 cases of cancer found in the study, the individual cancers were as follows:

* 18 infants had hematologic neoplasms (12.3 expected), 15 of which were acute lymphoblastic leukemia
* 15 infants had central nervous system neoplasms (8.1 expected), 7 of which were astrocytomas
* 2 infants had malignant retinal tumors (retinoblastoma) (1.25 expected)
* 6 infants had Langerhans cell histiocytosis (1 expected).

After adjustment for year of birth, the odds ratio for childhood cancer among infants who were born after IVF was 1.42.

The researchers acknowledge that the classification of Langerhans cell histiocytosis as a cancer is debatable: "Is it a malignant neoplastic disease or a reactive process?"

"Little is known about the epidemiology of Langerhans histiocytosis," the authors write.

Therefore, they performed an analysis of the total cancer risk that excluded the children with histiocytosis and found that the odds ratio went down to 1.34 — but remained statistically significant.

What's Driving the Increased Risk?

The investigators observed that the mothers of children born after IVF differed in many ways from the 2.4 million other women who gave birth in the study: maternal age was higher, there was a high percentage of first parity, fewer smoked, more had a high body mass index, and fewer were born outside Sweden.

Neither the differences between the 2 sets of mothers nor adjustment for these differences had any impact on the estimated risk, report the study authors, but neonatal characteristics did affect cancer risk.

There was an increased risk for cancer associated with preterm birth before week 37, a birth weight of 4500 g of higher, and a low Apgar score.

"Neonatal factors could act as intermediaries between the IVF procedure and cancer development," write the authors.

They also note that, in various studies, 2 neonatal factors have shown a "relatively constant association" with an increased childhood cancer risk: high birth weight and neonatal asphyxia.

Both factors were seen in this study. Neonatal asphyxia or oxygen treatment was indicated in the study by a low Apgar score.

Multiple births, which are a common complication in IVF pregnancies, did not seem to factor into the cancer risk in the study, report the authors.

The study was supported by a grant from the Evy and Gunnar Sandberg Foundation in Lund. The authors have disclosed no relevant financial relationships.

Pediatrics. 2010;126:e270-e276.