Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle.
Centre for Perinatal Medicine & Health, Department of Obstetrics & Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
JAMA Psychiatry. 2019 Jun 1;76(6):594-602. doi: 10.1001/jamapsychiatry.2019.0029.
The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero.
To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy.
DESIGN, SETTING, AND PARTICIPANTS: A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018.
Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection.
Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring.
A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero.
These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.
精神疾病的发育起源尚不完全清楚。虽然自闭症和精神分裂症的发展与胎儿期感染有关，但尚不清楚更常见的精神疾病，如抑郁症，是否可能在子宫内开始。
评估在怀孕期间因母亲感染而住院的胎儿暴露于任何感染的精神病理状况的风险。
设计、地点和参与者：总共观察了 1791520 名 1973 年 1 月 1 日至 2014 年 12 月 31 日期间在瑞典出生的儿童，使用链接的基于人群的登记册对他们进行了长达 41 年的观察。如果儿童出生时间太晚而无法提供人员时间、在有风险之前死亡或缺少特定模型数据，则将其排除在外。感染和精神科诊断是使用住院治疗的代码得出的。通过系统文献综述开发了有向无环图，以确定儿童精神病理状况的 Cox 比例风险回归模型。使用概率和简单偏差分析评估结果。统计分析于 2018 年 2 月 10 日至 10 月 17 日进行。
怀孕期间母亲感染住院、严重母亲感染和尿路感染。
在瑞典出生的 1791520 名儿童（48.6%为女性，51.4%为男性）从出生到 41 岁期间进行了观察，共 32125813 人年。在有向无环图的假设框架内，胎儿暴露于任何母亲感染都会增加儿童自闭症（危险比[HR]，1.79；95%置信区间[CI]，1.34-2.40）或抑郁症（HR，1.24；95%CI，1.08-1.42）的住院诊断风险。在严重的母亲感染（自闭症：HR，1.81；95%CI，1.18-2.78；抑郁症：HR，1.24；95%CI，0.88-1.73）或尿路感染（自闭症：HR，1.89；95%CI，1.23-2.90；抑郁症：HR，1.30；95%CI，1.04-1.61）后，自闭症和抑郁症的效应估计值相似，且结果稳健，不受中度未知混杂的影响。在有向无环图的假设框架内，感染与抑郁症之间的关系容易受到随访丢失的影响，但来自瑞典死亡登记处的单独数据表明，暴露于妊娠感染的个体自杀风险增加。没有证据表明暴露于感染的儿童会增加双相情感障碍或精神病的风险。
这些发现表明，胎儿在住院期间暴露于母亲感染会增加儿童生命期间自闭症和抑郁症的风险，但不会增加双相情感障碍或精神病的风险。这些结果强调了避免怀孕期间感染的重要性，因为感染可能会导致胎儿大脑受到轻微损伤，从而导致自闭症和抑郁症的发生。
