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Scientists comment on study, published in PLOS Medicine, on prenatal exposure to maternal depression and antidepressants and neurodevelopmental outcomes.
Prof Asma Khalil, Professor of Obstetrics and Maternal–Fetal Medicine, City St George’s, University of London, said:
“This is a substantial study with a useful strength: it links health and school records for more than 167,000 children and compares children whose mothers had recorded depression with and without an antidepressant prescription. In the adjusted analysis, special educational needs were estimated in about 24 out of 100 children whose mothers had recorded depression without an antidepressant prescription, compared with about 27 out of 100 whose mothers had both. That difference is worth studying, but it does not show that antidepressants caused it. The researchers could not measure how severe the mothers’ depression was, and women prescribed medication may have differed in important ways from those who were not.
“The press release acknowledges this uncertainty, although its references to ‘neurodevelopmental disorders’ need care: the main outcome was a broad measure of special educational needs, which is not the same as a clinical diagnosis. A prescription also does not establish that a medicine was taken throughout pregnancy. This study adds valuable evidence about the needs of children and families, but it cannot tell an individual woman whether taking or stopping an antidepressant would change her child’s developmental risk.”
Prof Chiara Nosarti, Professor of Neurodevelopment & Mental Health, King’s College London (KCL), said:
“This is an important study addressing a challenging question in maternal mental health. The findings suggest that children exposed to antidepressants during pregnancy had a slightly higher rate of special educational needs, but the increase was small, and these findings do not establish that antidepressants themselves caused the difference. Women who receive antidepressant treatment may have more severe or persistent depression, making it difficult to separate the effects of the underlying depression from those of its treatment.
“Importantly, maternal depression itself can be associated with children’s developmental and educational outcomes, and this is not limited to women with the most severe depression or those who take antidepressants. Supporting women who experience depressive symptoms during pregnancy, including mild symptoms, is therefore critical. Ensuring that women have access to appropriate support early on may help address their mental health needs and should be an important part of antenatal care.
“Further research is needed to better understand the contributions of maternal depression, its severity and its treatment to children’s longer-term outcomes. We also need to improve our mechanistic understanding of how maternal depression and its treatment during pregnancy may influence child development, so that we can better identify potential risks and protective factors and provide women with clearer evidence to inform decisions about their care.”
Prof Stella Chan, Charlie Waller Chair in Evidence-Based Psychological Treatment, University of Reading, said:
“This study examined the risk for neurodevelopmental disorders in children of mothers who experienced depression during pregnancy. Key findings suggested that there was a significant link, whether the mother received antidepressants or not during pregnancy, although there might be a small additional risk associated with those exposed to medications. As justly highlighted in the press release, this association could be due to many crucial factors not examined in this study, such as severity and family history of depression. It should also be pointed out that some neurodevelopmental disorders are heritable, and that some mothers in this study could have undiagnosed autism or other conditions that may have contributed to the risk. Furthermore, the wider psycho-social factors and environments have not been considered. In summary, the associations between these factors are highly complex with wide individual differences; as such, we should be cautious about making conclusions based on a single finding.
“The press release itself presents the findings of the study in a balanced way. It is very important that people understand the confounding factors in this study that may also have influenced the results, so that there can be no misunderstanding about what this study found. There was a link and the analyses were sound, but there were simply so many complex factors in this link, all potentially interacting with each other, it is very difficult to draw definitive conclusions.
“The key message is that we need to do what we can to support people with depression, and the findings in this study alone are not clear enough to steer pregnant women towards the decision of medication. I feel passionate about this topic because pregnant women are often receiving very conflicting and unclear guidance on medications of all kinds, and we shouldn’t add more pressure to them unless we have had very clear findings.”
Prof David Curtis, Honorary Professor, UCL Genetics Institute, University College London (UCL), said:
“Although this study shows that children of mothers who suffered depression or took antidepressants have increased rates of special educational needs, we cannot assume that this represents a causal relationship. These outcomes were also strongly associated with a number of confounding variables including deprivation, maternal age and smoking status. Although the researchers did their best to account for these confounders it would not be possible to completely negate their effects. Other factors which were not measured may also have contributed, such as alcohol and drug misuse, physical and mental health problems and help-seeking behaviour.
“In fact, for me it seems somewhat implausible that a mother being depressed in the two years before birth would somehow cause the child to be at subsequently increased risk of having learning difficulties. Typically, a depressive illness per se does not produce profound physiological changes such as might be expected to substantially disrupt foetal development. Alternative explanations seem more likely. A mother depressed in the years before delivery would be more likely to have subsequent episodes of depression and these subsequent episodes might impact a child’s psychosocial development. A mother with a previous diagnosis of depression might have more contact with support services which could result in a higher probability of problems with the child being detected. Or, as mentioned by the authors themselves, a mother abusing alcohol would be at increased risk of depression while also exposing the foetus to the harmful effects of alcohol in utero. There are quite a number of ways in which risk factors for maternal depression could overlap with risk factors for neurodevelopmental problems in the child.
“I think we may be seeing association rather than causation.”
Prof Angelica Ronald, Professor of Psychology and Genetics, University of Surrey, said:
“The writing in the press release is clear and suitably cautious. This sentence from the press release is incredibly important for the public understanding of this issue, “Our results don’t suggest that women should automatically stop taking their antidepressants because depression can harm both mother and baby if not treated. Women should always speak to their doctor about what is best in their situation.”
“I believe this is good quality research. The sample size is very large which means that the estimates are likely to be accurate for the population that was studied. The use of linked education and medical records is a big strength of the study.
“There is evidence from a range of sources that depression and neurodevelopmental conditions such as autism and ADHD share some genetic influences. This means we expect autism, ADHD and depression to run in the same families to some degree. This new study does not account for the fact that autism, ADHD and depression share some inherited (genetic) influences. Shared genetic influences might explain some of the associations found here between maternal depression in pregnancy and maternal use of antidepressants in pregnancy and offspring special educational needs. We cannot be sure that maternal use of antidepressants in pregnancy causes offspring special educational needs from these results alone. The authors are suitably cautious about their results.”
‘Prenatal exposure to maternal depression and antidepressants and neurodevelopmental outcomes: A population cohort study’ by Saraid McIlvride et al. was published in PLOS Medicine at 19:00 UK time on Tuesday 29 September.
DOI: 10.1371/journal.pmed.1004658
Declared interests
Prof Asma Khalil: “No relevant DOIs”
Prof Chiara Nosarti: “I do not have any COIs to declare”
Prof Stella Chan: “no conflict of interest”
Prof David Curtis: “I have no conflict of interest.”
Prof Angelica Ronald: “My research is funded by the Simons Foundation and UK Genetics Society”