A systematic review and meta-analysis published in The Lancet looks at antidepressant use in pregnancy and the risk of autism and ADHD in children.
Dr Alison Wright, President of the Royal College of Obstetricians and Gynaecologists, said:
“The RCOG welcomes this important systematic review and meta-analysis, which provides further evidence-based reassurance that antidepressant use during pregnancy is not associated with ADHD or autism in children.
“At least one in five women experience mental health problems during pregnancy or in the first year after birth and the consequences of untreated depression can be devastating. Suicide remains one of the leading causes of maternal death in the UK.
“All women deserve personalised, compassionate care, and this includes mental health. Women who are struggling should speak to their midwife, obstetrician, or GP who can discuss the options. Prompt and supportive care can make a profound difference, and no woman should have to suffer alone.”
Prof Catriona Waitt, NIHR Professor of Clinical Pharmacology and Global Health, University of Liverpool, said:
“This study highlights the importance of confounding by indication. Women with moderate to severe depression may be more likely to be prescribed antidepressants and more likely to have children with neurodevelopmental differences, independently of any medication effect. This underlines why carefully designed research is required in this area. Where such confounding is not accounted for, studies risk producing conclusions that overestimate harm. This can result in avoidance of medications that may be clinically important, potentially leaving maternal mental illness undertreated.”
Dr Anita Banerjee, Associate Professor in Obstetric Medicine, King’s COllege London, said;
“This study is timely. The most recent MBRRACE report on maternal deaths found that mental health disorders are the leading cause of maternal mortality in the postpartum period up to a year in the UK, reinforcing that undertreated maternal mental illness carries its own serious risks. As is highlighted in the BPS position statement, evidence of this kind is essential to support informed, shared decision-making between clinicians and patients.”
BPS Position statement: https://www.bps.ac.uk/fileadmin/uploads/bps/Policy_statements/BPS_Position_Statement-_Medications_in_Pregnancy_and_Breastfeeding__1_.pdf
Prof James Walker, Professor Emeritus Obstetrics and Gynaecology, University of Leeds, said:
“It is completely understandable that parents-to-be are concerned about whether the medicines they take in pregnancy could affect their baby. That worry has grown in recent years, especially around autism, with so many headlines pointing the finger at one exposure or another. So, a careful, large piece of research like this is exactly what is needed to help cut through the noise.
“The good news here is that the findings are reassuring. The researchers pulled together 37 studies covering more than 600,000 pregnancies where the mother took an antidepressant, and nearly 25 million where she did not. While children of mothers who took antidepressants in pregnancy were slightly more likely to be diagnosed with autism or ADHD, the most likely explanation is not the medication. It is the fact that these conditions run in families, both through genes and through the home environment children grow up in.
“This is a really important point that is easy to get wrong. If you simply compare children whose mothers took antidepressants with children whose mothers did not, you may find a difference. But that does not mean the medicine caused the difference. Mothers who are prescribed antidepressants are, by definition, more likely to have a mental health condition. Mental health conditions are partly inherited, and they sit on the same family tree as autism and ADHD. So, children of these mothers were already a bit more likely to be diagnosed with autism or ADHD, regardless of whether any medication was involved.
“What is impressive about this study is the lengths the researchers went to in order to test that idea. They compared brothers and sisters in the same family where one had been exposed to antidepressants in pregnancy and the other had not, keeping the family genes and home life broadly the same. They compared mothers who took antidepressants in pregnancy with mothers who had taken them before pregnancy but stopped, separating the effect of the medicine from the effect of the underlying depression. In a novel approach, they looked at what happened when fathers, rather than mothers, took antidepressants during the pregnancy. They found almost exactly the same small increase in autism and ADHD in those children. A father’s medication obviously cannot reach the baby in the womb, so this pattern is very hard to explain by anything other than shared family traits.
“Each of these checks pointed in the same direction: once you allow for family and parental factors, the apparent link between antidepressants in pregnancy and autism or ADHD largely disappears. There was also no sign that higher doses caused more harm than lower doses, which is another reason to doubt that the medicines themselves are to blame.
“There are some limitations to keep in mind. The authors themselves describe the overall strength of the evidence as low. Important things like income, smoking, alcohol use, and birthweight were not always measured in the original studies. Only two of the 37 studies reported the ethnicity of the families involved, and most were White, so we cannot be certain the findings apply equally to everyone. There was a small lingering signal for two older antidepressants, amitriptyline and nortriptyline, but these tend to be prescribed when depression is more severe or has not responded to other treatments, so this probably reflects how unwell those women were rather than a real problem with the drugs. More research is needed before drawing firm conclusions about those two specifically.
“The practical message is straightforward. Women with moderate or severe depression should not stop their antidepressants in pregnancy out of fear of causing autism or ADHD. Depression that goes untreated in pregnancy carries real risks of its own, for the mother, the pregnancy, and the developing baby, including a higher chance of premature birth, postnatal depression, and difficulties bonding with the baby. For milder depression, talking therapies and other non-medication approaches are usually tried first, in line with current guidelines. As always, decisions in pregnancy are personal and should be made with a clinician who knows the woman’s history.
“One last thing worth saying. This study quietly makes a bigger point: dads matter too. By showing that fathers’ mental health is part of the picture, the researchers are reminding us that supporting both parents, not just mothers, is good for the whole family, and good for children as they grow.”
‘Maternal and paternal antidepressant use before and during pregnancy and offspring risk of neurodevelopmental disorders: a systematic review and meta-analysis’ by Joe Kwun Nam Chan et al. was published in Lancet Psychiatry at 23:30 UK time on Thursday 14th May.
Declared interests
Dr Alison Wright: Co-director of a private company ObGyn Matters
Prof Catriona Waitt:
Member of the working group that developed the BPS position statement on ‘Medications in pregnancy and breastfeeding’
Paid employment or self-employment:
University of Liverpool
Infectious Diseases Institute, Makerere University
I get payment for Wellcome early career interview panel work
I get consultancy from Gates Design Analyse Communicate (DAC)
Grant funding:
Wellcome clinical research career development fellowship
NIHR Global Health Research Professorship
Gates
EDCTP
Voluntary appointments:
A couple of committees with UK Christian Medical Fellowship
Memberships of relevant professional bodies/ charities/ voluntary organisations/ lobbying organisations:
British Pharmacological Society – ambassador, clinical committee, engagement committee, content committee
BJCP international editor
Decision-making or advisory positions:
WHO HIV, Hepatitis and STI pregnancy working group
WHO TB and pregnancy/ breastfeeding research toolkit committee
IDSMB for GSK on a trial
Several other IDSMBs – but it is only the GSK one that comes with a contract and consultancy fee
Dr Anita Banerjee: Member of the working group that developed the BPS position statement on ‘Medications in pregnancy and breastfeeding’:
Prof James Walker: “I have no conflict of interests in this area.”