Maternal Vitamin D Status Determines
Bone Variables in the Newborn

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   J Clin Endocrinol Metab. 2010 (Apr); 95 (4): 1749–1757 ~ FULL TEXT

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H. T. Viljakainen, E. Saarnio, T. Hytinantti, M. Miettinen, H. Surcel, O.
Mäkitie, S. Andersson, K. Laitinen and C. Lamberg-Allardt

Department of Applied Chemistry and Microbiology,
Division of Nutrition, P.O. Box 66,
University of Helsinki,
FI-00014 Helsinki, Finland.
heli.viljakainen@helsinki.fi

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71% of Pregnant Moms Are Deficient in Vitamin D Vitamin D is important for the growth and development of bones and teeth. For this reason, vitamin D is an important growth nutrient for infants and children. Vitamin D is one of the primary regulators of calcium absorption, which is also important for proper bone health and development. Deficiencies are frequently found in individuals with or at risk for osteoporosis. Considering this relationship, vitamin D insufficiency may have an effect on bone strength. Maternal vitamin D levels may be responsible for programming neonatal skeletal development. The purpose of this study was to determine the association of mothers' vitamin D status with bone variables of their newborns. The cross-sectional study included 125 pregnant women. Researchers collected data from each of the participants, which included age, body mass index before pregnancy, pregnancy weight gain and total vitamin D intake. The researchers also collected blood samples from the mothers during the first trimester, two days postpartum and from the umbilical cords at birth to analyze serum 25-hydroxyvitamin D. It was found that although the mean total intake of vitamin D among the mothers met current recommendations, 71 percent of women and 15 percent newborns were deficient during pregnancy. These results suggest that efforts should be made to revise current nutrition recommendations for pregnant women since this may have a permanent effect on the well-being of their children. Thanks to NHI-on-Demand for the commentary!

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CONTEXT:   Vitamin D regulates 3% of the human genome, including effects on bone health throughout life. Maternal vitamin D status may program neonatal skeletal development. The objective here was to determine the association of mothers' vitamin D status with bone variables of their newborns.

SUBJECTS AND METHODS:   In a birth hospital, pregnant women (n = 125) participated in a cross-sectional study with a longitudinal follow-up of the pregnancy. The mean (sd) values for age, body mass index before pregnancy, pregnancy weight gain, and total vitamin D intake in mothers were 31 (4) yr, 23.5 (3.7) kg/m(2), 13.1 (4.3) kg, and 14.3 (5.8) microg, respectively. All newborns were full-term, 99% were appropriate for gestational age, and 53% were boys. Blood samples were collected from mothers during the first trimester and 2 d postpartum and from umbilical cords at birth for analysis of serum 25-hydroxyvitamin D (S-25-OHD), PTH, and bone remodeling markers. Bone variables were measured by pQCT at the 20% site of the newborn tibia on an average of 10 (11) d postpartum. Bone contour was analyzed with a single threshold of 180 mg/mm(3) for the detection of total bone mineral density (BMD), bone mineral content (BMC), and cross-sectional area (CSA).

RESULTS:   Mean S-25-OHD was 41.0 (13.6), 45.1 (11.9), and 50.7 (14.9) nmol/liter during the first trimester, postpartum, and in the umbilical cord, respectively. The median value of the individual means for first trimester and the 2-d postpartum S-25-OHD was 42.6 nmol/liter, which was used as cutoff to define two equal-sized groups. Groups are called below median and above median in the text. Newborns below median were heavier (P = 0.05), and 60% were boys. Tibia bone mineral content was 0.047 (95% confidence interval, 0.011-0.082) g/cm higher (P = 0.01), and cross-sectional area was 12.3 (95% confidence interval, 2.0-22.6) mm(2) larger (P = 0.02), but no difference in bone mineral density was observed, above median compared with below median group. These results were adjusted for newborn Z-score birth weight, maternal height, and newborn age at the measurement. A positive, significant correlation was observed between remodeling markers in mothers at different time points and above median group in the cord.

CONCLUSIONS:   Although the mean total intake of vitamin D among mothers met current Nordic recommendations, 71% of women and 15% of newborns were vitamin D deficient during the pregnancy. Our results suggest that maternal vitamin D status affects bone mineral accrual during the intrauterine period and influences bone size. More efforts should be made to revise current nutrition recommendations for pregnant women that may have permanent effects on the well-being of children.

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From the Full-Text Article:

Discussion

To our knowledge, this is the first study to examine the effect of maternal vitamin D status on skeletal variables of the newborn. The results show that newborns whose mothers had mean 25-OHD concentration during pregnancy above the median (S-25-OHD at least 42.6 nmol/liter) had 13.9% higher tibial BMC and 16.3% higher CSA compared with those below median. However, tibia volumetric BMD did not differ between these groups. Our study supports the importance of vitamin D in fetal growth.

Dietary intake of vitamin D and sunshine exposure determine vitamin D status [2]. The average maternal total intake of vitamin D was 14.3 µg, which is in line with current Nordic recommendations [35] for pregnant women (10 µg, or 400 IU). Of the mothers, 80% used vitamin D supplements, which are currently recommended for pregnant and lactating women during the winter [36]. All supplements contained only D3 which is favored in supplements in Finland. Despite the recommended dietary intake, most of the mothers were vitamin D deficient throughout the pregnancy. At the individual level, FFQ may overestimate actual intake of vitamin D somewhat, but at the group level the results are in accordance with 4-d food records. Together with repeated S-25-OHD measurements, the retrospective assessment of vitamin D intake adds to the value of this study [37]. The total intake of vitamin D strongly correlated with S-25-OHD in postpartum and cord samples. The cord blood S-25-OHD was 103 (16)% of the maternal postpartum level, and a strong positive correlation existed between the two, in accordance with a review by Greer [8]. In earlier Finnish studies, cord 25-OHD has been at least 20% lower than maternal 25-OHD concentration [7, 38], possibly due to differences in vitamin D status and the analytical methods used.

Based on umbilical cord 25-OHD concentration, 14.8% of newborns were categorized as having deficient (S-25-OHD <37.5 nmol/liter), 37.5% as insufficient (37.5 nmol/liter = S-25-OHD < 50 nmol/liter), and 48.2% as sufficient (S-25-OHD >50 nmol/liter) vitamin D status when using pediatric reference values [39]. Similarly, of the mothers, 71 and 27% had deficient and insufficient vitamin D status, respectively, during the pregnancy. We used a mean value of the first trimester and d-2 postpartum 25-OHD concentrations to describe the overall maternal vitamin D status. Vitamin D status here improved from first trimester to postpartum by an average of 6 nmol/liter, probably due to seasonal variation. The cumulative effect of 25-OHD on bone development is displayed by using the mean maternal value. As proposed by Namgung and Tsang [40], first-trimester 25-OHD is related to newborn bone variables, but the physiology of bone mineral accrual [17, 29, 41] supports focusing on postpartum 25-OHD.

Newborns of mothers above median had higher BMC and larger CSA in the tibia than newborns of mothers below median. The difference between the groups was significant and clinically relevant, based on least significant change. Our results are independent of birth weight, gender, maternal height, or age at measurement, and they suggest that maternal vitamin D status affects both bone mineral accrual and bone size during the intrauterine period. In previous studies, maternal vitamin D status has been linked to long bone growth in newborns [17], and seasonal variation has been shown to account for 8% difference in whole-body BMC in newborns in Korea, but not in the United States [22]. However, animal models exploiting knockout mice (vitamin D receptor, 1-a hydroxylase) yield inconsistent results regarding the role of vitamin D in growth of the fetus or bone mineral accrual [29]. In earlier studies, 25-OHD concentration during late pregnancy has been associated with whole-body and lumbar spine BMC, bone age, and BMD at the age of 9 yr [18]. Maternal vitamin D status during gestation is suggested to program skeletal development [10] and body composition in offspring [16]. Tracking of bone mass occurs throughout life [18, 20, 42], emphasizing the importance of our results.

The highest levels of bone remodeling markers were measured in the cord sample, as also reported by others [7, 43, 44]. Högler et al. [45] showed that the concentrations of bone remodeling markers (carboxy-terminal collagen crosslinks, osteocalcin, and BALP) in the cord at birth were similar to those in peripheral venous samples at d 2, proving that bone remodeling markers in the cord reflect bone turnover in neonates. We found that bone remodeling accelerated during pregnancy, but similar to findings of other studies [44, 46], maternal bone turnover was not associated with newborn bone turnover. The effect of growth per se on bone turnover is minimal in full-term neonates [46, 47]. However, turnover time of the remodeling markers in the fetus and newborn may be altered, which may complicate the prediction of results. Maternal smoking [43] and winter season [22] increase resorption markers in cord blood.

Interestingly, maternal intake of vitamin D correlated inversely with TRACP in the cord. Vitamin D supplementation tends to decrease bone resorption in vitamin D-inadequate newborns [48] and adolescents [24]. In otherwise healthy adults, vitamin D maintains coupled bone turnover, which is reflected in the significant positive correlation of bone formation and resorption markers [49, 50]. The correlation is a robust model that does not take into account the time lag between resorption and formation. In the present study, we used cell-specific bone remodeling markers derived from active osteoblasts (BALP) and osteoclasts (TRACP). A coupled bone turnover was observed in mothers at different time points and above median group in the cord. In newborns whose mothers were below median of vitamin D status, bone turnover was not coupled in umbilical cord, suggesting altered bone turnover. Daily vitamin D supplementation (25–30 µg) during the last trimester to Indian immigrants in England resulted in a lower level of alkaline phosphatase in the umbilical cord relative to the placebo group [48].

A positive correlation was observed between maternal postpartum PTH and newborn Z-score birth length. Furthermore, the change in maternal vitamin D status during pregnancy and the infant’s birth length and birth weight Z-scores correlated negatively, suggesting that mothers with larger babies had lower vitamin D status during the postpartum period than mothers with smaller babies. Brooke et al. [48] reported less small-for-gestational-age babies in the vitamin D-treated group compared with the placebo group. It is proposed that higher maternal PTH occurs due to increased mineral demands of bigger babies [17, 51]. Thus, greater fetal growth may influence maternal vitamin D status, which is supported by findings of Holmes et al. [52]. We observed that lower maternal vitamin D status was associated with a slightly higher birth weight Z-score (P = 0.07), but not length, after adjusting for confounding factors (parental size, maternal weight gain during pregnancy, solar exposure, total intake of vitamin D, and initial 25-OHD concentration). Our study was, however too small to allow any final conclusions to be drawn about whether fetal growth affects maternal vitamin D status.

Our findings indicate that more efforts should be directed toward correcting vitamin D status during pregnancy—first, to achieve full genetic growth potential of the offspring [9], and second, to maximize bone mineral accrual during the fetal period [41]. Effective vitamin D supplementation of infants aged between 2 wk and 3 yr of age, which started in the 1940s, has overcome rickets in Finland. However, a discrepancy in vitamin D status between the intrauterine and early postnatal periods may still interfere with skeletal development [9].

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Conclusions

Although total intake of vitamin D among mothers met current Nordic recommendations, the majority of the women throughout the pregnancy and newborns at birth had vitamin D status below 50 nmol/liter. Maternal vitamin D deficiency is associated with adverse outcomes during pregnancy [13, 14, 15]. Our results suggest that maternal vitamin D status affects fetal bone mineral accrual during the intrauterine period and influences bone size and mineral content at birth. Besides bone health, impaired maternal vitamin D status is hypothesized to modify long-term risk for several chronic diseases. More efforts should be made to revise current nutrition recommendations for pregnant women. In addition, intervention studies targeted to pregnant women are warranted.

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