Webb R T, Pickles A R, King-Hele S A, Appleby L, Mortensen P B, Abel K M
Centre for Women's Mental Health Research, The University of Manchester, Manchester, UK.
Psychol Med. 2008 Oct;38(10):1495-503. doi: 10.1017/S0033291707002280. Epub 2007 Dec 13.
Few large studies describe links between maternal mental illness and risk of major birth defect in offspring. Evidence is sparser still for how effects vary between maternal diagnoses and no previous study has assessed risk with paternal illnesses.
A population-based birth cohort was created by linking Danish national registers. We identified all singleton live births during 1973-1998 (n=1.45 m), all parental psychiatric admissions from 1969 onwards, and all fatal birth defects until 1 January 1999. Linkage and case ascertainment were almost complete. Relative risks were estimated using Poisson regression.
Risk of fatal birth defect was elevated in relation to history of any maternal admission and also with affective disorders specifically, although the strongest effect found was with maternal schizophrenia. The rate was more than doubled in this group compared to the general population [relative risk (RR) 2.34, 95% confidence interval (CI) 1.45-3.77], which also represented a significant excess risk compared with all other admitted maternal disorders (p=0.018). Risk of death from causes other than birth defect was no higher with schizophrenia than with other maternal conditions. There was no elevation in risk of fatal birth defect if the father was admitted with schizophrenia or any other psychiatric diagnosis.
There are many possible explanations for a higher risk of fatal birth defect with maternal schizophrenia and affective disorder. These include genetic effects directly linked with maternal illness, lifestyle factors (diet, smoking, alcohol and drugs), poor antenatal care, psychotropic medication toxicity, and gene-environment interactions. Further research is needed to elucidate the causal mechanisms.
很少有大型研究描述孕产妇精神疾病与后代重大出生缺陷风险之间的联系。关于不同孕产妇诊断之间影响如何变化的证据更为稀少，且此前没有研究评估父亲患病时的风险。
通过链接丹麦国家登记册创建了一个基于人群的出生队列。我们确定了1973年至1998年期间所有单胎活产（n = 145万）、1969年起所有父母的精神病住院情况以及截至1999年1月1日所有致命出生缺陷。链接和病例确定几乎是完整的。使用泊松回归估计相对风险。
与任何孕产妇住院史相关的致命出生缺陷风险升高，特别是与情感障碍相关，尽管发现最强的影响是与孕产妇精神分裂症相关。与一般人群相比，该组的发生率增加了一倍多[相对风险（RR）2.34，95%置信区间（CI）1.45 - 3.77]，与所有其他已确诊的孕产妇疾病相比，这也代表了显著的额外风险（p = 0.018）。精神分裂症患者因出生缺陷以外原因导致的死亡风险并不高于其他孕产妇情况。如果父亲被诊断为精神分裂症或任何其他精神疾病，致命出生缺陷的风险没有升高。
孕产妇精神分裂症和情感障碍导致致命出生缺陷风险较高有许多可能的解释？？这些包括与孕产妇疾病直接相关的遗传效应、生活方式因素（饮食、吸烟、饮酒和药物）、产前护理不佳、精神药物毒性以及基因 - 环境相互作用。需要进一步研究以阐明因果机制。
