Maternal Use of Estrogen Hormonal Contraception Just Before Pregnancy – A Risk for Childhood Leukemia?

In a well done and very interesting study in Lancet Oncology, Danish researchers have identified an association between use of estrogen-containing oral contraceptives in the three months prior to pregnancy or during pregnancy and the risk of childhood leukemia in the offspring of that pregnancy.

The study’s conclusions are strengthened by the fact that the data come from three reliable nationwide Danish databases –  one registering births, one registering cancers and the other registering prescriptions –  and included over a million children born between 1996 and 2014, with a median of 9 years follow up from birth.

How high is the risk?

The hazard ratio for childhood leukemia was about 50%-70% higher among children born to women taking estrogen-containing contraceptives in the three months prior to or during pregnancy, compared to that in the offspring of women not using these contraceptives immediately before or during pregnancy. The risk was confined to non-lymphoid leukemias.

Because the overall risk of leukemias is low (most children do NOT develop leukemia), the actual risk translates to one extra case of leukemia for every 50,000 potentially exposed children, or in Denmark, about 4% of leukemia cases over the 9 years studied.

That’s not a large risk, but it is worth looking at.

Which hormonal contraceptives were implicated?

The risk for childhood leukemia was only found for use of estrogen-containing oral contraceptives in the 3 months just prior to pregnancy or during pregnancy. No association was found for non-oral preparations, but there were few cases of these.

No increase in risk was found for ever use of any hormonal contraceptive prior to the 3 months immediately preceding pregnancy.

No risk was found for use of non-estrogen containing hormonal contraception (think the mini-pill, levonorgestrel IUD and Depo-Provera) at any time, even immediately before or during pregnancy.

Is this really true?

Let’s be clear. Association is NOT causation. But it is a signal that warrants further study and a plausible explanation.

In this case there is a biologically plausible mechanism, in that estrogens can inhibit certain enzymes that protect DNA from cancer causing mutations. There are also other proposed mechanisms.

But there could be alternate explanations for the study’s results. For example, what if the mother carries and transmits to her child a genetic predisposition that not only increases the risk of leukemia, but also causes her to have heavy periods that necessitated her use of birth control pills? Or if by chance, in this study, more women with a genetic predisposition happened to take birth control pills? The researchers did not have genetic information on both mother and child, and that’s important.

Results of other studies exploring the birth control pill-leukemia link have been mixed.

So we need further studies.

But still, it begs the question – what should we do until we have the results of these further studies? After all that can take years, and women are getting pregnant now.

What should you do with this information?

What you should NOT do is let this study scare you away from using birth control pills to prevent pregnancy. Oral contraceptives continue to be among the safest, most effective ways to prevent pregnancy. Not to mention their benefits in treating irregular, painful or heavy menses, endometriosis, acne, hirsutism and in some women, PMS.

But until we have further data, I don’t see any harm in playing it safe – which means stopping estrogen-containing hormonal birth control and using either the mini-pill or a barrier method of birth control (such as condoms or diaphragm) in the 3 months prior to attempting pregnancy.  (Theres no reason to change to a long acting method such as Depo-Provera or the IUD for just 3 months.)

If you’re an inconsistent oral contraceptive user worried you may become pregnant due to missed pills, this may be another reason why you may want to change to a more effective method such as the IUD for long term use.

As they say, talk to your doctor.  

With my own patients, I tend to take an “If it’s not broken, don’t fix it” approach to birth control. Which means, if you are happy and healthy using estrogen-containing birth control, don’t let this be a reason to stop using it. But do have a plan for transitioning off when you want to become pregnant.

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References

  • Pombo-de-Oliveira MS. Maternal hormonal contraception and childhood leukaemi. Comment. Lancet Oncology 19:10. p1261-1262. Oct 1, 2018.
  • Hargreave M, Mørch LS, Andersen KK, Winther JF, Schmiegelow K, Kjaer SK.
    Maternal use of hormonal contraception and risk of childhood leukaemia: a nationwide, population-based cohort study.Lancet Oncology. 2018; (published online Sept 6. http://dx.doi.org/10.1016/S1470-2045(18)30479-0.)

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