Svahn M F, Hargreave M, Nielsen T S S, Plessen K J, Jensen S M, Kjaer S K, Jensen A
Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.
Child and Adolescent Mental Health Center, Mental Health Services, Capital Region, DK-2100 Copenhagen Ø, Denmark Department of Clinical Medicine, Faculty of Medicine and Health Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
Hum Reprod. 2015 Sep;30(9):2129-37. doi: 10.1093/humrep/dev172. Epub 2015 Jul 22.
Is the risk of hospital admission or outpatient contact for mental disorders increased in children born to women with fertility problems compared with children born to women without fertility problems?
We found an increased risk of hospital admission or outpatient contact for mental disorders in children born to women with fertility problems.
Few studies have investigated the risk of mental disorders in children born after fertility treatment and although some studies have pointed to an increased risk, others found no association. The inconsistent results may be due to methodological constraints in many previous studies, including small sample size and short follow-up, resulting in imprecise risk estimates and lack of information on risk patterns of mental disorders in adulthood.
STUDY DESIGN, SIZE, DURATION: This nationwide retrospective register-based cohort study included all 2 412 721 children born in Denmark between 1969 and 2006. All children were followed from date of birth until date of hospital contact for a mental disorder, date of emigration, date of death or 31 December 2009, whichever occurred first.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Information concerning maternal fertility status for all children in the cohort was obtained by linkage to the Danish Infertility Cohort, which contains data on nearly all women with fertility problems in Denmark since 1963. A total of 124 269 (5%) children were born to women with fertility problems and 2 288 452 (95%) to women without fertility problems. To identify children hospitalized for a mental disorder, the cohort was linked to the Danish Psychiatric Central Research Registry. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk of hospital admission or outpatient contact for various groups of mental disorders, including any mental disorder and all 11 main discharge diagnostic groups, classified according to the International Classification of Diseases, version 10.
During a mean follow-up period of 21 years (range, 0-40 years), 168 686 (7%) children were admitted to hospital or had an outpatient contact for a mental disorder. Children born to women with fertility problems had a significantly higher risk of any mental disorder (HR 1.23; 95% CI 1.20-1.26) and for most of the 11 main discharge groups, including schizophrenia (HR 1.16; 95% CI 1.07-1.27), mood (affective) disorders (HR 1.21; 95% CI 1.15-1.28) and disorders of psychological development (HR 1.15; 95% CI 1.09-1.21) as well as the subgroup of attention-deficit/hyperactivity disorders (HR 1.36; 95% CI 1.29-1.45) compared with children born to women without fertility problems. The risk estimates did not change markedly when analyses were performed separately for mental disorders diagnosed during childhood (0-19 years) and in young adulthood (20-40 years).
LIMITATIONS, REASON FOR CAUTION: The true risk of mental disorders may be somewhat underestimated, as only severe disorders requiring hospital admission or outpatient contact were considered as events. Furthermore, we could not determine whether the increased risks observed were due to factors related to the underlying infertility or to fertility treatment procedures.
This is the first report on mental disorders in adulthood among children born to women with fertility problems. Furthermore, we have assessed the risk of several severe mental disorders not previously studied (e.g. neurotic, stress-related and somatoform disorders and disorders of adult personality and behaviour). These important findings should be investigated further in large epidemiological studies designed to differentiate between factors related to fertility treatment and to the underlying infertility.
STUDY FUNDING/COMPETING INTERESTS: The study was supported by internal funding from the Unit of Virus, Lifestyle and Genes at the Danish Cancer Society Research Center. All authors report no conflicts of interest.
与未患生育问题的女性所生孩子相比,患生育问题的女性所生孩子患精神障碍而住院或门诊就诊的风险是否增加?
我们发现,患生育问题的女性所生孩子患精神障碍而住院或门诊就诊的风险增加。
很少有研究调查过接受生育治疗后出生儿童患精神障碍的风险,尽管一些研究指出风险增加,但其他研究未发现关联。结果不一致可能是由于许多先前研究存在方法学限制,包括样本量小和随访时间短,导致风险估计不准确,且缺乏成年期精神障碍风险模式的信息。
研究设计、规模、持续时间:这项基于全国性回顾性登记的队列研究纳入了1969年至2006年在丹麦出生的所有2412721名儿童。所有儿童从出生之日起随访至因精神障碍住院就诊之日、移民之日、死亡之日或2009年12月31日,以先发生者为准。
参与者/材料、环境、方法:通过与丹麦不孕症队列建立联系,获取了队列中所有儿童母亲的生育状况信息,该队列包含自1963年以来丹麦几乎所有有生育问题女性的数据。共有124269名(5%)儿童的母亲有生育问题,2288452名(95%)儿童的母亲无生育问题。为确定因精神障碍住院的儿童,该队列与丹麦精神病学中央研究登记处建立了联系。使用Cox比例风险模型估计母亲生育状况与各类精神障碍住院或门诊就诊风险之间关联的风险比(HRs)和95%置信区间(CIs),包括任何精神障碍以及根据《疾病和有关健康问题的国际统计分类》第10版分类的所有11个主要出院诊断组。
在平均21年(范围0 - 40年)的随访期内,168686名(7%)儿童因精神障碍住院或门诊就诊。母亲有生育问题的儿童患任何精神障碍的风险显著更高(HR 1.23;95% CI 1.20 - 1.26),在11个主要出院组中的大多数组中也是如此,包括精神分裂症(HR 1.16;95% CI 1.07 - 1.27)、心境(情感)障碍(HR 1.21;95% CI 1.15 - 1.28)、心理发育障碍(HR 1.15;95% CI 1.09 - 1.2)以及注意力缺陷/多动障碍亚组(HR 1.36;95% CI 1.29 - 1.45),与母亲无生育问题的儿童相比。当分别对儿童期(0 - 19岁)和青年期(20 - 40岁)诊断的精神障碍进行分析时,风险估计没有明显变化。
局限性、谨慎理由:精神障碍的真实风险可能被略微低估,因为仅将需要住院或门诊就诊的严重障碍视为事件。此外,我们无法确定观察到的风险增加是由于与潜在不孕症相关的因素还是生育治疗程序。
这是关于有生育问题女性所生孩子成年期精神障碍的首份报告。此外,我们评估了几种先前未研究过的严重精神障碍的风险(如神经症、与应激相关和躯体形式障碍以及成人个性和行为障碍)。这些重要发现应在旨在区分生育治疗相关因素和潜在不孕症相关因素的大型流行病学研究中进一步调查。
研究资金/利益冲突:该研究由丹麦癌症协会研究中心病毒、生活方式和基因部门的内部资金支持。所有作者均声明无利益冲突。