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Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study

BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f2059 (Published 19 April 2013) Cite this as: BMJ 2013;346:f2059

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Re: Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study

The increased risk of autism with maternal antidepressant use during pregnancy may relate to previous use of progestins.1

Progesterone or progestins can cause depression by increasing monoamine oxidase levels in the late secretory phase of a normal cycle or during medication with a powerful progestin.2 Monoamine oxidase inhibitor drugs are antidepressants.

In 2010 Ann Brit Wirehn and colleagues studied nearly a million Swedish women.3 In all age groups progestin-only takers had significant increased risks of antidepressant use but the highest risk was in 16-19 year olds. Combined hormonal contraceptives also increased antidepressants use in 16-19 year-olds. The risk of antidepressants use for past hormone takers was not assessed. As past takers also have increases in depression, adding these women to never taker controls minimized the increased risk of antidepressant use for hormone ever- takers.

The RCGP study enrolled Pill takers and controls between 1968 and 1972 when depressive neurosis increased by 1.3 (p<0.01) in takers and by 1.28 (p>0.01) in ex-takers. Hospital admission for depression increased by 3.61 in ex-takers (p>0.01) and suicide was the commonest cause of death in takers.4 In 1984 the relative risks for attempted suicide was 1.42 for current takers and 2.12 for former takers compared with controls.5 Mortality in the RCGP study was under recorded as a quarter of the women originally enrolled were lost to follow-up before deaths began to be flagged on the NHS Central Register in 1977. The 2010 RCGP mortality study still found higher rates of violent deaths for ever-takers of oral contraceptives.6

There are already reasons to suspect a link between maternal hormonal contraceptive use and autism with increased toxic DNA adducts found in some women taking hormones and also in some autistic children.7 Now there is also a link with maternal antidepressant use.

1 Rai D, Leer BJ, Dalman C, Golding J, Lewis G, Magnusson C. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013;346:f2059.

2 Grant ECG. Pryce Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. BMJ 1968;3:777-80.

3 Wiréhn AB, Foldemo A, Josefsson A, Lindberg M. Use of hormonal contraceptives in relation to antidepressant therapy: A nationwide population-based study. Eur J Contracept Reprod Health Care. 2010;15:41-7.

4 Royal College of General Practitioners. Oral Contraceptives and Health. 1974 Pitman Medical, London.

5 Royal College of General Practitioners, Oral contraception study: some recent observations 1984;11 759-86.

6 Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners' Oral Contraception Study. BMJ 2010; 340: c927

7 Grant ECG. McLaren-Howard J. Re: The effects of toxic metals in autistic children. http://bmj.com/cgi/eletters/329/7466/588-b#74117, 13 Sep 2004.

Competing interests: No competing interests

29 April 2013
Ellen CG Grant
Physician and medical gynaecologist
Retired
Kingston upon Thames, Surrey