Maternal preeclampsia is associated with reduced adolescent off-spring hip bone mineral density in a UK population based birth cohort

Introduction: A suboptimal intrauterine environment has been postulated to have adverse long-term health effects, including an increased risk of osteoporosis. Since preeclampsia (PE) and to a lesser extent gestational hypertension (GH) are associated with impaired placental function we postulated that these represent hitherto unrecognised risk factors for reduced bone mineral density (BMD) of the offspring. Objective: To investigate if exposure to PE or GH in utero is associated with BMD of the offspring as measured in late adolescence. Methods: Mother-offspring pairs from the UK population based cohort study 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. Results: 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 and lean mass), PE was negatively associated with BMD at the hip (-0.30SD (-0.50, -0.10)) (SD difference (95% confidence interval)). This association was not attenuated by further adjustment for gestational age and birthweight, which were hypothesized to be on the causal pathway. There was also weak evidence for a negative association between PE and total body BMD (-0.17SD (-0.36, 0.02)), whereas no relationship was evident at the spine (-0.11SD (-0.30, 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.
Conclusion: Modest negative associations from exposure to PE, but not GH may represent a hitherto unrecognised risk factor for low BMD. Further exploration of the causal relationship of the in utero environment on subsequent offspring bone health is required.