Bone Mineral Density In Offspring Research Articles

The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis.

A systematic review and meta-analysis was performed to assess the effect of pregnancy vitamin D supplementation on offspring bone mineral density (BMD) in childhood. A literature search was conducted for published RCTs of antenatal vitamin D supplementation with assessment of offspring BMD or bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) using MEDLINE and EMBASE up to 13th July 2022. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Study findings were grouped in two age groups of offspring assessment: neonatal period and early childhood (3-6years). Random-effects meta-analysis of the effect on BMC/BMD at 3-6years was performed using RevMan 5.4.1, yielding standardised mean difference (SMD) (95% CI). Five RCTs were identified with offspring assessment of BMD or BMC; 3250 women were randomised within these studies. Risk of bias was low in 2 studies and "of concern" in 3. Supplementation regimes and the control used (3 studies used placebo and 2 used 400IU/day cholecalciferol) varied, but in all studies the intervention increased maternal 25-hydroxvitamin D status compared to the control group. Two trials assessing BMD in the neonatal period (total n = 690) found no difference between groups, but meta-analysis was not performed as one trial represented 96.4% of those studied at this age. Three trials assessed offspring whole-body-less-head BMD at age 4-6years. BMD was higher in children born to mothers supplemented with vitamin D [0.16 SD (95% confidence interval 0.05, 0.27), n = 1358] with a smaller effect on BMC [0.07 SD (95% CI - 0.04, 0.19), n = 1351]. There are few RCTs published to address this question, and these are inconsistent in methodology and findings. However, meta-analysis of three trials suggests moderate- to high-dose vitamin D supplementation in pregnancy might increase offspring BMD in early childhood, but further trials are required to confirm this finding. (Prospero CRD42021288682; no funding received).

No effect of maternal calcium intake and bone resorption during pregnancy on offspring bone mineral density at age 5 years.

Suboptimal bone mineral density in childhood can result in osteoporosis later in life. We reported previously that lower calcium intake during pregnancy was associated with higher maternal bone resorption during pregnancy and that lower maternal dietary calcium and higher maternal bone resorption in pregnancy were associated with lower maternal bone mineral density (BMD) 5 years later. The current study sought to investigate the effect of both maternal dietary calcium intake and maternal bone resorption during pregnancy on offspring BMD at 5 years. Data collected as part of the ROLO longitudinal cohort study (n = 103, mother-child dyads) were used in the current analysis. ROLO started as a randomised controlled trial of a low glycemic index diet during second pregnancy in women with macrosomia in first pregnancy in order to prevent recurrence of macrosomia. Maternal dietary intakes were assessed using 3-day food diaries completed during each trimester of pregnancy. Bone resorption in early and late pregnancy was calculated through urinary excretion of cross-linked N-telopeptides (uNTX). Offspring whole-body BMD at 5 years was measured using dual-energy X-ray absorptiometry. Offspring BMD at 5 years correlated with offspring body mass index (r = .385; p < .001) and offspring BMD was higher in boys than girls (t = 2.91; p = .004). Offspring BMD at 5 years was not associated with either maternal calcium intake or uNTX during pregnancy, after controlling for offspring body mass index and offspring sex. Offspring BMD at 5 years is not associated with either maternal calcium intake or maternal bone resorption during pregnancy.

Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta-analysis.

Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566). No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long‐term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high‐dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.

Maternal Diet, Nutritional Status, and Birth-Related Factors Influencing Offspring's Bone Mineral Density: A Narrative Review of Observational, Cohort, and Randomized Controlled Trials.

There is growing evidence that bone health may be programmed in the first years of life. Factors during the prenatal period, especially maternal nutrition, may have an influence on offspring’s skeletal development and thus the risk of osteoporosis in further life, which is an increasing societal, health and economic burden. However, it is still inconclusive which early life factors are the most important and to what extent they may affect bone health. We searched through three databases (PubMed, Google Scholar, Cochrane Library) and after eligibility criteria were met, the results of 49 articles were analyzed. This narrative review is an overall summary of up-to-date studies on maternal diet, nutritional status, and birth-related factors that may affect offspring bone development, particularly bone mineral density (BMD). Maternal vitamin D status and diet in pregnancy, anthropometry and birth weight seem to influence BMD, however other factors such as subsequent growth may mediate these associations. Due to the ambiguity of the results in the analyzed studies, future, well-designed studies are needed to address the limitations of the present study.

Nutrients, Diet, and Other Factors in Prenatal Life and Bone Health in Young Adults: A Systematic Review of Longitudinal Studies.

Optimizing skeletal health in early life has potential effects on bone health later in childhood and in adulthood. We aimed to evaluate the existing evidence that maternal exposures during pregnancy have an impact on the subsequent bone health among offspring in young adults aged between 16 and 30 years. The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42019126890). The search was conducted up to 2 April 2019. We included seven observational prospective cohort studies that examined the association between maternal dietary factors, vitamin D concentration, age, preeclampsia, and smoking with any bone indices among offspring. The results indicated that high concentrations of maternal vitamin D; low fat intake; and high intakes of calcium, phosphorus, and magnesium may increase the bone mineral density in offspring at age 16. Evidence also suggests that the offspring of younger mothers may have a higher peak bone mass. It remains inconclusive whether there is an influence of preeclampsia or maternal smoking on bone health among young adults. Our assessment of internal validity warrants a cautious interpretation of these results, as all of the included studies were judged to have serious risks of bias. High-quality studies assessing whether prenatal prognostic factors are associated with bone health in young adults are needed.

Association between maternal smoking and child bone mineral density: a systematic review and meta-analysis.

Maternal smoking during pregnancy has detrimental effects on fetal development. The current review examined the differences in offspring's bone mineral density (BMD) between mothers smoked during pregnancy and those who did not. A systematic review and meta-analysis on the studies investigating the influence of maternal smoking during pregnancy on children or neonates' bone measures published up to October 30, 2018, was performed. BMD results measured at different body sites were pooled and then fixed or random effect models were used based on the presence of heterogeneity. The desired pooled effect size was the offspring's BMD mean difference with 95% confidence interval between smoker and non-smoker mothers. Sensitivity analysis was performed for birth weight and current weight, two important mediator/confounders causing heterogeneity. Overall, eight studies consisting of 17,931 participants aged from infancy to 18years were included. According to the fixed effect model, the mean of BMD in offspring whose mothers smoked during pregnancy was 0.01g/cm2 lower than those with non-smoker mothers (95% CI = - 0.02 to - 0.002). However, subgroup meta-analysis adjusted for birth weight and current weight demonstrated no significant mean difference between BMD of children with smoker and non-smoker mothers (d = 0.06, 95% CI = -0.04 to 0.16, p value = 0.25 and d = - 0.005, 95% CI = - 0.01 to 0.004, p value = 0.28, respectively). According to available studies, it is suggested that maternal smoking during pregnancy does not have direct effect on the offspring's BMD. Instead, this association might be confounded by other factors such as placental weight, birth weight, and current body size of children.

Maternal serum retinol, 25(OH)D and 1,25(OH)2D concentrations during pregnancy and peak bone mass and trabecular bone score in adult offspring at 26-year follow-up.

BackgroundVitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear.Method and findingsForty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986–88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) μmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 μmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS.ConclusionsThis is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD.

Loss of maternal EED results in postnatal overgrowth

BackgroundInvestigating how epigenetic information is transmitted through the mammalian germline is the key to understanding how this information impacts on health and disease susceptibility in offspring. EED is essential for regulating the repressive histone modification, histone 3 lysine 27 tri-methylation (H3K27me3) at many developmental genes.ResultsIn this study, we used oocyte-specific Zp3-Cre recombinase (Zp3Cre) to delete Eed specifically in mouse growing oocytes, permitting the study of EED function in oocytes and the impact of depleting EED in oocytes on outcomes in offspring. As EED deletion occurred only in growing oocytes and females were mated to normal wild type males, this model allowed the study of oocyte programming without confounding factors such as altered in utero environment. Loss of EED from growing oocytes resulted in a significant overgrowth phenotype that persisted into adult life. Significantly, this involved increased adiposity (total fat) and bone mineral density in offspring. Similar overgrowth occurs in humans with Cohen-Gibson (OMIM 617561) and Weaver (OMIM 277590) syndromes, that result from de novo germline mutations in EED or its co-factor EZH2, respectively. Consistent with a role for EZH2 in human oocytes, we demonstrate that de novo germline mutations in EZH2 occurred in the maternal germline in some cases of Weaver syndrome. However, deletion of Ezh2 in mouse oocytes resulted in a distinct phenotype compared to that resulting from oocyte-specific deletion of Eed.ConclusionsThis study provides novel evidence that altering EED-dependent oocyte programming leads to compromised offspring growth and development in the next generation.

Nutritional Programming of Bone Structure in Male Offspring by Maternal Consumption of Citrus Flavanones

Maternal exposure to hesperidin (HSP) and naringin (NAR) during pregnancy and lactation transiently compromised bone mineral density (BMD) and bone structure at the proximal tibia in female CD-1 offspring. We examined whether maternal consumption of HSP + NAR during pregnancy and lactation compromises BMD, bone structure, and bone strength in male CD-1 offspring. Male CD-1 offspring, from mothers fed a control diet (CON, n = 10) or a 0.5% HSP + 0.25% NAR diet (HSP + NAR, n = 8) for 5 weeks before mating and throughout pregnancy and lactation, were weaned and fed CON until 6 months of age. In vivo micro-computed tomography (µCT) measured tibia BMD and structure at 2, 4, and 6 months of age. Ex vivo µCT measured femur and lumbar vertebrae (LV) structure at age 6 months. Ex vivo BMD (femur, LV) and biomechanical strength (femur and tibia midpoint, femur neck) were assessed at age 6 months by dual energy x-ray absorptiometry and strength testing, respectively. At all ages, HSP + NAR offspring had greater (p < 0.05) proximal tibia cortical structure compared to CON offspring. At age 4 months, proximal tibia trabecular structure was greater (p < 0.05) than CON offspring. At age 6 months, femur neck and LV trabecular structure were greater (p < 0.05) than CON offspring. Our results demonstrate that unlike our previous study of female offspring, maternal consumption of HSP + NAR resulted in greater bone structure at the proximal tibia in male CD-1 offspring that persisted to 6 months of age. Thus, maternal programming of offspring BMD and bone structure from consumption of HSP + NAR occurred as a sex-specific response.

25-hydroxyvitamin D concentrations during fetal life and bone health in children aged 6 years: a population-based prospective cohort study

25-hydroxyvitamin D (25[OH]D) concentrations during fetal life might have long-lasting effects on skeletal development, but results from previous studies are inconsistent. We investigated the associations of maternal and fetal 25(OH)D concentrations with childhood bone health. In a prospective multiethnic population-based cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), pregnant women living in the study area with an expected delivery date between April 1, 2002, and Jan 1, 2006, were eligible for participation in the study at our research centre in the Erasmus MC-Sophia Children's Hospital. We measured maternal 25(OH)D concentrations during mid-pregnancy (at a median of 20·4 weeks gestation [IQR 19·9-21·1]) and fetal 25(OH)D concentrations at birth (at a median of 40·1 weeks gestation [39·3-41·0]). We measured total-body bone mineral density, bone mineral content (BMC), area-adjusted BMC, and bone area using dual-energy X-ray absorptiometry (DXA) in offspring at 6 years of age. We examined associations using multivariable linear regression models, adjusted for several sociodemographic and lifestyle variables, and for child's height. We enrolled 9901 mother-and-child pairs and obtained both mid-pregnancy maternal 25(OH)D concentrations and offspring DXA scans at age 6 years in 4815 pairs. Severe maternal 25(OH)D deficiency (<25 nmol/L) during mid-pregnancy was associated with higher offspring BMC (4·71 g, 95% CI 1·09 to 8·33; p=0·011) and larger bone area (7·54 cm2, 2·99 to 12·11; p=0·001) at age 6 years, compared with maternal 25(OH)D sufficiency (≥50 nmol/L) during mid-pregnancy. However, in a subgroup of children with available data on 25(OH)D concentrations at 6 years (n=3034), such associations for BMC (4·67 g, -0·05 to 9·39; p=0·052) and bone area (5·25 cm2, -0·41 to 10·91; p=0·069) were no longer significant after adjustment for the child's own 25(OH)D concentrations. No associations were seen between maternal 25(OH)D concentrations in mid-pregnancy and offspring bone mineral density (1·07 mg/cm2, -1·84 to 3·99; p=0·47) or area-adjusted BMC (-1·58 g, -4·72 to 1·61; p=0·32), and the association with skeletal parameters at 6 years did not differ by maternal BMI, maternal calcium intake, child sex, or weight status. Similar associations were seen with fetal 25(OH)D concentrations at birth. We found inverse associations between 25(OH)D concentrations during fetal life with BMC and bone area in childhood, but these associations were no longer significant after adjustment for childhood 25(OH)D status. Our data suggest that 25(OH)D concentrations during childhood might be more relevant for bone outcomes than than 25(OH)D concentrations during fetal life. Erasmus University Medical Center, Organization for Health Research and Development (ZonMw), Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport.

Brief Report: Does Medication Use or Disease Activity During Pregnancy in Patients With Rheumatoid Arthritis Affect Bone Density in Their Prepubertal Offspring?

ObjectivePrednisone use and active disease are associated with reduced bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Either or both of these factors may be inevitable during pregnancy in women with RA, but it is unknown whether they variables influence the BMD of the offspring. This study was undertaken to investigate whether medication use or disease activity during pregnancy in RA patients influences the BMD of their prepubertal offspring.MethodsMothers (n = 255) participated in a prospective cohort study of RA and pregnancy, and 108 children of these mothers (ages 5–10 years) were included in this followup study. Information on features known to influence BMD in children, i.e., calcium intake, physical activity, serum 25‐hydroxyvitamin D level, sex, height, and weight, was collected. In addition, pre‐ and postnatal variables known to influence BMD, i.e., gestational age, maternal smoking, birth weight, postnatal rate of growth, and type of feeding, were recorded. Independent variables were prednisone use, sulfasalazine use, and RA disease activity during pregnancy.ResultsWe found no association of BMD in the children with either prednisone use or RA disease activity during pregnancy, even after correcting for all known associated variables. Sulfasalazine use during pregnancy had a positive effect on the total‐body BMD of the offspring (difference in standard deviation score 0.53, P = 0.005).ConclusionOur findings indicate that neither medication use nor high RA disease activity during pregnancy is associated with decreased BMD in offspring at age ∼7 years. The maternal benefit of medication use for RA during pregnancy outweighs the effect on BMD in the offspring.

Maternal Vitamin D Status During Pregnancy and Bone Mass in Offspring at 20 Years of Age: A Prospective Cohort Study

It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum samples collected at 18 weeks gestation were assayed for 25-hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L; 132 women (38.7%) were vitamin D-deficient (25OHD <50 nmol/L). After adjustment for season of sample collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6-32.7) g for BMC and 4.6 (95% CI, 0.1-9.1) mg/cm(2) for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm(2) , p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life.