Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark3Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada4Center for Primary Care and Outcomes Research, Stanford University, Stanford, California5Clinical Excellence Research Center, Stanford University School of Medicine, Stanford, California.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
JAMA. 2016 Dec 20;316(23):2515-2524. doi: 10.1001/jama.2016.18425.
Giving birth to a child with a major birth defect is a serious life event for a woman, yet little is known about the long-term health consequences for the mother.
To assess whether birth of an infant born with a major congenital anomaly was associated with higher maternal risk of mortality.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study (n = 455 250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly (41 508) between 1979 and 2010, with follow-up until December 31, 2014. A comparison cohort (413 742) was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity, and year of infant's birth.
Live birth of an infant with a major congenital anomaly as defined by the European Surveillance of Congenital Anomalies classification system.
Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality. Hazard ratios (HRs) were adjusted for marital status, immigration status, income quartile (since 1980), educational level (since 1981), diabetes mellitus, modified Charlson comorbidity index score, hypertension, depression, history of alcohol-related disease, previous spontaneous abortion, pregnancy complications, smoking (since 1991), and body mass index (since 2004).
Mothers in both groups were a mean (SD) age of 28.9 (5.1) years at delivery. After a median (IQR) follow-up of 21 (12-28) years, there were 1275 deaths (1.60 per 1000 person-years) among 41 508 mothers of a child with a major congenital anomaly vs 10 112 deaths (1.27 per 1000 person-years) among 413 742 mothers in the comparison cohort, corresponding to an absolute mortality rate difference of 0.33 per 1000 person-years (95% CI, 0.24-0.42), an unadjusted HR of 1.27 (95% CI, 1.20-1.35), and an adjusted HR of 1.22 (95% CI, 1.15-1.29). Mothers with affected infants were more likely to die of cardiovascular disease (rate difference, 0.05 per 1000 person-years [95% CI, 0.02-0.08]; adjusted HR, 1.26 [95% CI, 1.04-1.53]), respiratory disease (rate difference, 0.02 per 1000 person-years [95% CI, 0.00-0.04]; adjusted HR, 1.45 [95% CI, 1.01-2.08]), and other natural causes (rate difference, 0.11 per 1000 person-years [95% CI, 0.07-0.15]; adjusted HR, 1.50 [95% CI, 1.27-1.76]).
In Denmark, having a child with a major congenital anomaly was associated with a small but statistically significantly increased mortality risk in the mother compared with women without an affected child. However, the clinical importance of this association is uncertain.
对于女性来说，生育有重大出生缺陷的孩子是一件严重的生活事件，但对于母亲来说，长期健康后果知之甚少。
评估婴儿出生时患有重大先天异常是否与母亲死亡风险增加有关。
设计、地点和参与者：这项基于人群的队列研究（n=455250 名女性）使用个体水平的丹麦注册数据，对 1979 年至 2010 年间出生的患有重大先天异常的婴儿（41508 例）的母亲进行了研究，并随访至 2014 年 12 月 31 日。通过对每个患有受影响婴儿的母亲进行随机抽样，构建了一个对照队列（413742 例），并按母亲年龄、产次和婴儿出生年份匹配了最多 10 名母亲。
定义为欧洲先天性畸形监测系统的活产婴儿有重大先天性异常。
主要结局为全因死亡率。次要结局包括病因特异性死亡率。风险比（HR）调整了婚姻状况、移民状况、收入四分位（自 1980 年起）、教育水平（自 1981 年起）、糖尿病、改良 Charlson 合并症指数评分、高血压、抑郁症、酒精相关疾病史、先前自然流产、妊娠并发症、吸烟（自 1991 年起）和体重指数（自 2004 年起）。
两组母亲的分娩年龄平均（SD）为 28.9（5.1）岁。中位（IQR）随访 21（12-28）年后，41508 名患有重大先天性异常婴儿的母亲中有 1275 人死亡（每 1000 人年 1.60 人），413742 名对照队列母亲中有 10112 人死亡（每 1000 人年 1.27 人），绝对死亡率差异为 0.33/1000 人年（95%CI，0.24-0.42），未调整 HR 为 1.27（95%CI，1.20-1.35），调整 HR 为 1.22（95%CI，1.15-1.29）。患有受影响婴儿的母亲更有可能死于心血管疾病（差异率为 0.05/1000 人年[95%CI，0.02-0.08]；调整 HR 为 1.26[95%CI，1.04-1.53]）、呼吸道疾病（差异率为 0.02/1000 人年[95%CI，0.00-0.04]；调整 HR 为 1.45[95%CI，1.01-2.08]）和其他自然原因（差异率为 0.11/1000 人年[95%CI，0.07-0.15]；调整 HR 为 1.50[95%CI，1.27-1.76]）。
在丹麦，与没有受影响孩子的女性相比，母亲生育患有重大先天性异常的孩子与母亲死亡风险略有但统计学上显著增加相关。然而，这种关联的临床重要性尚不确定。
