Xu Xiaoqing, Ritz Beate, Cockburn Myles, Lombardi Christina, Heck Julia E
Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA.
Department of Neurology, School of Medicine, UCLA, Los Angeles, CA.
Paediatr Perinat Epidemiol. 2017 Mar;31(2):157-164. doi: 10.1111/ppe.12338. Epub 2017 Jan 26.
Preeclampsia is a major cause of adverse effects on fetal health. We examined associations between fetal exposure to preeclampsia and subsequent odds of childhood cancers.
We obtained childhood cancer cases (n = 13 669) diagnosed at 5 years old or younger between 1988 and 2012 from the California Cancer Registry and linked them to birth certificates. Controls (n = 271 383) were randomly selected from all California births and frequency matched to cases by birth year. We obtained data regarding preeclampsia during pregnancy, labour, and delivery from the medical worksheet of the electronic birth record. We used unconditional logistic regression models with stabilised inverse probability weights to estimate the effect of preeclampsia on each subtype of childhood cancer, taking into account potential confounding by pregnancy characteristics. Marginal structural models were fitted to assess the controlled direct effects of preeclampsia, independent of preterm delivery and NICU admission.
Although a null association was observed for all cancer subtypes combined (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.9, 1.2), preeclampsia was found to be associated with increased odds of two histological subtypes of germ cell tumours: seminomas (OR 8.6, 95% CI 1.9, 38.4) and teratoma (OR 3.0, 95% CI 1.7, 5.4), but not yolk sac tumours in children. Odds remained elevated after adjusting for preterm delivery and NICU admission. Increases in odds were also observed for hepatoblastoma, however this association was attenuated in marginal structural models after accounting for NICU admission.
These findings suggest that maternal preeclampsia is associated with higher odds of some rare childhood cancers and may shed light on new aetiological factors for these cancers.
子痫前期是对胎儿健康产生不良影响的主要原因。我们研究了胎儿暴露于子痫前期与儿童期癌症后续发病几率之间的关联。
我们从加利福尼亚癌症登记处获取了1988年至2012年间诊断为5岁及以下的儿童癌症病例(n = 13669),并将其与出生证明相关联。对照组(n = 271383)从加利福尼亚所有出生记录中随机选取,并按出生年份与病例进行频数匹配。我们从电子出生记录的医疗工作表中获取了孕期、分娩期子痫前期的数据。我们使用带有稳定逆概率权重的无条件逻辑回归模型来估计子痫前期对儿童期癌症各亚型的影响,同时考虑到妊娠特征可能产生的混杂因素。拟合边际结构模型以评估子痫前期独立于早产和新生儿重症监护病房(NICU)入院情况的受控直接效应。
尽管所有癌症亚型合并分析时未观察到关联(比值比(OR)为1.0,95%置信区间(CI)为0.9,1.2),但发现子痫前期与生殖细胞肿瘤的两种组织学亚型发病几率增加有关:精原细胞瘤(OR 8.6,95% CI 1.9,38.4)和畸胎瘤(OR 3.0,95% CI 1.7,5.4),但与儿童卵黄囊瘤无关。在调整早产和NICU入院情况后,发病几率仍然升高。肝母细胞瘤的发病几率也有所增加,然而在考虑NICU入院情况后,该关联在边际结构模型中有所减弱。
这些发现表明,母亲子痫前期与某些罕见儿童期癌症的较高发病几率相关,可能为这些癌症的新病因因素提供线索。