Hannam Kimberly, Lawlor Debbie A, Tobias Jon H
Musculoskeletal Research Unit, University of Bristol, Bristol, UK.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
J Bone Miner Res. 2015 Sep;30(9):1684-91. doi: 10.1002/jbmr.2506. Epub 2015 May 14.
A suboptimal intrauterine environment has been postulated to have adverse long-term health effects, including an increased risk of osteoporosis. Because preeclampsia (PE) and to a lesser extent gestational hypertension (GH) are associated with impaired placental function, we postulated that these represent hitherto unrecognized risk factors for reduced bone mineral density (BMD) of the offspring. The objective of this study was to investigate if exposure to PE or GH in utero is associated with BMD of the offspring as measured in late adolescence. Mother-offspring pairs from the UK population-based cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), were investigated (n = 3088 with relevant data). Multivariable linear regression was used to examine associations between PE/GH and total body, spine, and total hip BMD at age 17 years. Of the 3088 mother-offspring pairs, 2% (n = 60) of the mothers fulfilled criteria for PE and 14% (n = 416) for GH. In confounder-adjusted analyses (ie, age of scan, gender, maternal factors, including BMI, offspring height, fat mass, and lean mass), PE was negatively associated with BMD at the hip (SD difference -0.30; 95%CI, -0.50 to -0.10). This association was not attenuated by further adjustment for gestational age and birth weight, which were hypothesized to be on the causal pathway. There was also weak evidence for a negative association between PE and total body BMD (SD difference -0.17; 95% CI, -0.36 to 0.02), whereas no relationship was evident at the spine (SD difference -0.11; 95% CI, -0.30 to 0.09). In contrast, a positive association of GH with offspring total body, hip, and spine BMD attenuated to the null with adjustment for confounders, in particular confounding via the maternal and offspring adiposity/size and the link between the two. Modest negative associations from exposure to PE, but not GH may represent a hitherto unrecognized risk factor for low BMD. Further exploration of the causal relationship of the in utero environment on subsequent offspring bone health is required.
据推测，子宫内环境欠佳会对长期健康产生不利影响，包括骨质疏松风险增加。由于子痫前期（PE）以及程度较轻的妊娠期高血压（GH）与胎盘功能受损有关，我们推测这些是迄今为止未被认识到的后代骨密度（BMD）降低的风险因素。本研究的目的是调查子宫内暴露于PE或GH是否与青春期后期测量的后代骨密度有关。对来自英国基于人群的队列研究“埃文父母与儿童纵向研究”（ALSPAC）的母婴对进行了调查（n = 3088，有相关数据）。采用多变量线性回归来检验PE/GH与17岁时全身、脊柱和全髋骨密度之间的关联。在3088对母婴对中，2%（n = 60）的母亲符合PE标准，14%（n = 416）符合GH标准。在混杂因素调整分析（即扫描年龄、性别、母亲因素，包括体重指数、后代身高、脂肪量和瘦体重）中，PE与髋部骨密度呈负相关（标准差差异 -0.30；95%置信区间，-0.50至 -0.10）。进一步调整胎龄和出生体重后，这种关联并未减弱，胎龄和出生体重被认为处于因果路径上。也有微弱证据表明PE与全身骨密度呈负相关（标准差差异 -0.17；95%置信区间，-0.36至0.02），而在脊柱方面无明显关系（标准差差异 -0.11；95%置信区间，-0.30至0.09）。相比之下，GH与后代全身、髋部和脊柱骨密度的正相关在调整混杂因素后减弱至无关联，尤其是通过母亲和后代肥胖/体型以及两者之间的联系产生的混杂。暴露于PE而非GH产生的适度负相关可能代表了一种迄今为止未被认识到的低骨密度风险因素。需要进一步探索子宫内环境与后代后续骨骼健康之间的因果关系。
