Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm Sweden.
Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health, McGill University Faculty of Medicine, Montreal, Canada.
Int J Epidemiol. 2019 Feb 1;48(1):297-306. doi: 10.1093/ije/dyy196.
Small-for-gestational-age (SGA) birth is commonly used as a proxy for fetal growth restriction, but also includes constitutionally small infants. Genetic factors account for almost half of the risk of SGA birth. We estimated perinatal risks of SGA birth using both population-based and within-sibling analyses, where the latter by design controls for shared genetic factors and maternal environmental factors that are constant across pregnancies.
This was a prospective nationwide cohort study of 2 616 974 singleton infants born in Sweden between January 1987 and December 2012, of whom 1 885 924 were full siblings. We estimated associations between severe or moderate SGA (<3rd percentile and 3rd to <10th percentiles, respectively) and risks of stillbirth, neonatal mortality and morbidity, using both population-based and within-sibling analyses. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated in stillbirth analyses, whereas relative risks (RRs) were used for analyses of neonatal outcomes.
Compared with non-SGA births (>10th percentile), the HR (95% CI) of stillbirth was 18.5 (95% CI 17.4-19.5) among severe SGA births in the population analysis and 22.5 (95% CI 18.7-27.1) in the within-sibling analysis. In non-malformed infants, RRs for neonatal mortality in moderate and severe SGA infants were similarly increased in both population and within-sibling analyses. In term non-malformed infants (≥37 weeks), SGA-related RRs of several neonatal morbidities were higher in within-sibling than in population analyses.
Perinatal risks associated with fetal growth restriction are more accurately estimated from analyses of SGA in which genetic factors are accounted for.
小胎龄儿（SGA）出生通常被用作胎儿生长受限的替代指标，但也包括先天身材较小的婴儿。遗传因素几乎占 SGA 出生风险的一半。我们使用基于人群的和同胞内分析来估计 SGA 出生的围产期风险，后者通过设计控制了在整个妊娠过程中保持不变的共同遗传因素和母体环境因素。
这是一项在瑞典进行的前瞻性全国队列研究，纳入了 1987 年 1 月至 2012 年 12 月间出生的 2616974 例单胎婴儿，其中 1885924 例为同胞。我们使用基于人群的和同胞内分析来估计严重或中度 SGA（分别<第 3 百分位和第 3 至<第 10 百分位）与死产、新生儿死亡率和发病率的风险之间的关联。在死产分析中，使用危害比（HR）和 95%置信区间（CI）来估计，而在新生儿结局分析中，使用相对风险（RR）。
与非 SGA 出生（>第 10 百分位）相比，在人群分析中，严重 SGA 出生的死产 HR（95%CI）为 18.5（95%CI 17.4-19.5），而在同胞内分析中为 22.5（95%CI 18.7-27.1）。在非畸形婴儿中，中度和严重 SGA 婴儿的新生儿死亡率 RR 在人群和同胞内分析中均增加。在足月非畸形婴儿（≥37 周）中，同胞内分析中与 SGA 相关的几种新生儿疾病的 RR 高于人群分析。
从考虑遗传因素的 SGA 分析中，可以更准确地估计与胎儿生长受限相关的围产期风险。
