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Updated: Jun 2, 2026

Culturing and Measuring Fetal and Newborn Murine Long Bones
Published on: April 26, 2019
Insights into the programming of bone development from the Avon Longitudinal Study of Parents and Children (ALSPAC)
Colin D Steer1, Jonathan H Tobias
1Centre for Child and Adolescent Health and Academic Rheumatology, Southmead Hospital, University of Bristol, United Kingdom.
Insights
In utero nutrition impacts childhood bone development. Maternal vitamin D and folate status positively influence bone mineral content, area, and density, independent of birth weight effects.
Area of Science:
- Pediatric Bone Health
- Prenatal Nutrition
- Skeletal Development
Background:
- In utero nutrition significantly influences fetal development, with potential long-term effects on skeletal health.
- Understanding these prenatal factors is crucial for optimizing bone mass accrual in childhood.
Purpose of the Study:
- To investigate the associations between proxy measures of in utero nutrition and bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) in children.
- To explore the independent effects of birth weight, maternal vitamin D status, and maternal folate intake on childhood bone development.
Main Methods:
- Utilized data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
- Assessed BMC, BA, and BMD at age 9.9 years.
- Examined associations with birth weight, maternal ultraviolet B (UVB) exposure (proxy for vitamin D), and maternal folate intake, with adjustments for body size and genetic factors (MTHFR genotype).
Main Results:
- Positive associations were found between birth weight and childhood BMC, BA, and BMD, largely explained by body size.
- An inverse association between birth weight and BMD was observed after adjusting for height and weight, suggesting a potential negative influence.
- Maternal UVB exposure was positively related to BMC, BA, and BMD, with effects on skeletal size and mass independent of longitudinal growth.
- Maternal folate intake showed a positive association with spine BMD, independent of body size, potentially mediated by maternal MTHFR genotype.
Conclusions:
- Childhood bone development is related to in utero nutritional status.
- Maternal vitamin D and folate status during pregnancy appear to have independent positive effects on offspring bone mass.
- Birth weight's influence on childhood bone density is complex, with potential negative effects after accounting for body size.
Abstract:
We examined associations between proxy measures of in utero nutrition and total body bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) assessed at age 9.9 y in the Avon Longitudinal Study of Parents and Children (ALSPAC). There were positive relations between birth weight and BMC, BA, and BMD. These associations were explained by the co-association of birth weight with body size in later childhood. In height- and weight-adjusted analyses, an inverse association was observed between birth weight and BMD at age 9.9 y, which suggests that birth weight had a negative influence on bone mass after relations with bone and body size were taken into account. In analyses of associations between bone mass at age 9 y and background ultraviolet B exposure during the third trimester of pregnancy (a proxy measure for maternal vitamin D status), maternal ultraviolet B exposure was positively related to BMC, BA, and BMD. After adjustment for height, these associations were only partially attenuated, which suggests that maternal ultraviolet B exposure affected skeletal size and mass independently of longitudinal growth, possibly by the increase of periosteal expansion. There was a positive relation between maternal folate intake and BMD of the spine subregion independent of body size. Although a co-association with folate intake in childhood could explain this relation, the maternal methylenetetrahydrofolate reductase (MTHFR) genotype affected spine BMD independently of the child MTHFR genotype, which suggests that maternal folate status has an independent effect on bone development of offspring. Together, these results confirm that there is a relation between bone development in childhood and several proxy measures for nutritional status in utero.
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