Department of Social Policy, London School of Economics and Political Science, London, UK; Max Planck Institute for Demographic Research, Rostock, Germany.
Population Research Unit, University of Helsinki, Helsinki, Finland.
Lancet. 2019 Mar 23;393(10177):1225-1232. doi: 10.1016/S0140-6736(18)31863-4. Epub 2019 Jan 14.
Children born after medically assisted reproduction are at higher risk of adverse birth outcomes than are children conceived naturally. We aimed to establish the extent to which this excess risk should be attributed to harmful effects of treatment or to pre-existing parental characteristics that confound the association.
We used data from Finnish administrative registers covering a 20% random sample of households with at least one child aged 0-14 years at the end of 2000 (n=65 723). We analysed birthweight, gestational age, risk of low birthweight, and risk of preterm birth among children conceived both by medically assisted reproduction and naturally. First, we estimated differences in birth outcomes by mode of conception in the general population, using standard multivariate methods that controlled for observed factors (eg, multiple birth, birth order, and parental sociodemographic characteristics). Second, we used a sibling-comparison approach that has not been used before in medically assisted reproduction research. We compared children conceived by medically assisted reproduction with siblings conceived naturally and, thus, controlled for all observed and unobserved factors shared by siblings.
Between 1995 and 2000, 2776 (4%) children in our sample were conceived by medically assisted reproduction; 1245 children were included in the sibling comparison. Children conceived by medically assisted reproduction had worse outcomes than did those conceived naturally, for all outcomes, even after adjustments for observed child and parental characteristics-eg, difference in birthweight of -60 g (95% CI -86 to -34) and 2·15 percentage point (95% CI 1·07 to 3·24) increased risk of preterm delivery. In the sibling comparison, the gap in birth outcomes was attenuated, such that the relation between medically assisted reproduction and adverse birth outcomes was statistically and substantively weak for all outcomes-eg, difference in birthweight of -31 g (95% CI -85 to 22) and 1·56 percentage point (95% CI -1·26 to 4·38) increased risk of preterm delivery.
Children conceived by medically assisted reproduction face an elevated risk of adverse birth outcomes. However, our results indicate that this increased risk is largely attributable to factors other than the medically assisted reproduction treatment itself.
European Research Council, the Academy of Finland, and the Signe and Ane Gyllenberg Foundation.
通过医学辅助生殖技术出生的儿童比自然受孕出生的儿童发生不良出生结局的风险更高。我们旨在确定这种额外风险在多大程度上归因于治疗的有害影响，或归因于混淆关联的预先存在的父母特征。
我们使用了来自芬兰行政登记处的数据，这些数据覆盖了 2000 年底至少有一个 0-14 岁儿童的家庭的 20%随机样本（n=65723）。我们分析了通过医学辅助生殖技术和自然受孕所生育的儿童的出生体重、胎龄、低出生体重风险和早产风险。首先，我们使用标准的多变量方法估计了普通人群中不同受孕方式的出生结局差异，该方法控制了观察到的因素（例如，多胎、出生顺序和父母的社会人口统计学特征）。其次，我们使用了一种以前在医学辅助生殖研究中未使用过的同胞比较方法。我们将通过医学辅助生殖技术受孕的儿童与自然受孕的同胞进行比较，从而控制了同胞之间共享的所有观察到和未观察到的因素。
在 1995 年至 2000 年期间，我们样本中的 2776 名（4%）儿童是通过医学辅助生殖技术受孕的；1245 名儿童纳入了同胞比较。即使在调整了儿童和父母的观察特征后，通过医学辅助生殖技术受孕的儿童的结局也比自然受孕的儿童差，所有结局均如此，例如，出生体重差异为-60g（95%CI-86 至-34）和早产风险增加 2.15 个百分点（95%CI 1.07 至 3.24）。在同胞比较中，出生结局的差距减弱，因此，医学辅助生殖与不良出生结局之间的关系在所有结局方面均具有统计学意义和实质性意义减弱，例如，出生体重差异为-31g（95%CI-85 至 22）和早产风险增加 1.56 个百分点（95%CI 1.26 至 4.38）。
通过医学辅助生殖技术受孕的儿童面临不良出生结局的风险增加。然而，我们的结果表明，这种增加的风险主要归因于医学辅助生殖治疗本身以外的因素。
欧洲研究理事会、芬兰科学院和 Signe 和 Ane Gyllenberg 基金会。
