• 배경
  • 임신 중 항우울제 사용 사례 60만 건을 분석한 메타 분석 결과가 15일 아침, '랜싯 정신의학'에 발표됐습니다.
    • 논문 제목: Maternal and paternal antidepressant use before and during pregnancy and offspring risk of neurodevelopmental disorders: a systematic review and meta-analysis
    • 5월 15일 07시 30분 엠바고 해제
  • 임신 중 산모의 약 사용은 언제나 조심스러운 일입니다. 항우울제 사용과 아동의 신경발달장애 위험 역시 염려하는 산모가 많습니다. 하지만 임신 중 항우울제 복용을 중단하는 것 또한 재발 위험 증가로 인해 위험할 수 있는 만큼, 항우울제 복용의 안전성은 큰 관심을 모으고 있습니다.
    • 하지만 이런 중요성에 비해, 이 주제를 조사한 이전 메타분석은 약 10년 전에 수행돼 오래됐으며, 연구 대상 수가 적고 추가적인 요인을 통제하지 못했다는 한계가 있었습니다.
  • 홍콩 연구팀은 항우울제를 사용한 60만 건 이상의 임신 사례를 분석한 37개 연구를 이용해 대규모 메타분석을 실시했습니다.
  • 연구 결과, 산모의 정신 건강 및 기타 요인을 고려했을 때 임신 중 항우울제 사용과 아이의 자폐스펙트럼장애 및 ADHD 사이에 유의미한 연관성은 없는 것으로 나타났습니다. 
  • 연구팀은 일부 나타는 연관성은 다른 요인이 원인이라고 밝혔습니다.
    • 교란 변수를 고려하기 전 연구에서는 임신 중 항우울제 사용과 아동의 자폐 또는 ADHD 사이에 약한 연관성이 있었습니다. 
      • 정신 건강 질환과 같은 주요 요인을 통제하기 전 분석 결과, 임신 중 어머니의 항우울제 복용은 ADHD 발병 위험을 35%, 자폐증 발병 위험을 69% 증가시켰습니다.
        
    • 하지만, 연관성은 임신 전 어머니의 항우울제 사용과 임신 중 아버지의 항우울제 사용에서도 나타났습니다. 
      • 임신 중 아버지의 항우울제 복용은 ADHD 위험을 46%, 자폐 위험을 28% 증가시키는 것과 관련이 있었습니다.
        
    • 연구팀은 약물 자체보다는 부모의 정신 건강 및 유전적 요인을 반영하는 것으로 보인다고 설명했습니다.
  • 연구팀은 "흔히 사용되는 항우울제가 아이의 자폐나 ADHD와 같은 신경발달장애 위험을 증가시키지 않는다는 안심할 만한 증거를 제공하는 연구"라며 "중증 우울증을 앓고 있는 여성의 경우, 의사와 환자는 임신 중 항우울제 치료를 지속하는 것의 잠재적 위험과 이점, 그리고 치료받지 않은 우울증의 잠재적 위험성을 신중하게 비교 검토해야 한다"고 밝혔습니다.

• 전문가 의견 요청 내용

  • 내용 해설 (결과에서 흥미롭거나 주목할 부분, 다른 논문이나 기존 연구와의 차별성 등)

  • 이번 논문의 의의 또는 한계, 향후 전망과 연구 과제, 결과 해석 상 주의할 점

  • 한국에서 특별히 주목해야 할 부분(국내 학계의 관련 연구, 한국 내 처방 경향에 대한 의견, 향후 국내에서 진행하면 좋을 연구 등)

  • 국내 전문가 및 해외 SMC 수집 의견을 전달합니다.

• 엠바고는 5월 15일 07시 30분(KST) 해제됐습니다. 자유롭게 활용 가능합니다.
• 되도록 원문을 그대로 활용해주시길 부탁드립니다.
• SMCK를 꼭 인용할 필요는 없습니다. 만약 인용 출처가 필요한 경우, 아래 형식을 따를 수 있습니다.
  • "ㅇㅇㅇ(전문가)는 한국과학기술미디어센터에 ㅁㅁㅁ라고 말했다."

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.”

Declared interests