Fetal Skeletal Growth Research Articles

Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trial

Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at <20 weeks gestation) to either placebo (n = 230) or calcium supplements (1500 mg calcium/day in 3 divided doses; n = 231). Growth parameters in utero were assessed with serial ultrasound scans. Birthweight, length, head, abdominal and thigh circumferences were recorded at delivery. No differences were found in fetal biometric measurements recorded at 20, 24, 28, 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not. Similarly, neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups. We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth.

Implications of vitamin D deficiency in pregnancy and lactation

Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism in children and adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels (>or=32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D metabolism and the implications of vitamin D deficiency in pregnancy and lactation.

A principal components approach to parent-to-newborn body composition associations in South India.

BackgroundSize at birth is influenced by environmental factors, like maternal nutrition and parity, and by genes. Birth weight is a composite measure, encompassing bone, fat and lean mass. These may have different determinants. The main purpose of this paper was to use anthropometry and principal components analysis (PCA) to describe maternal and newborn body composition, and associations between them, in an Indian population. We also compared maternal and paternal measurements (body mass index (BMI) and height) as predictors of newborn body composition.MethodsWeight, height, head and mid-arm circumferences, skinfold thicknesses and external pelvic diameters were measured at 30 ± 2 weeks gestation in 571 pregnant women attending the antenatal clinic of the Holdsworth Memorial Hospital, Mysore, India. Paternal height and weight were also measured. At birth, detailed neonatal anthropometry was performed. Unrotated and varimax rotated PCA was applied to the maternal and neonatal measurements.ResultsRotated PCA reduced maternal measurements to 4 independent components (fat, pelvis, height and muscle) and neonatal measurements to 3 components (trunk+head, fat, and leg length). An SD increase in maternal fat was associated with a 0.16 SD increase (β) in neonatal fat (p < 0.001, adjusted for gestation, maternal parity, newborn sex and socio-economic status). Maternal pelvis, height and (for male babies) muscle predicted neonatal trunk+head (β = 0. 09 SD; p = 0.017, β = 0.12 SD; p = 0.006 and β = 0.27 SD; p < 0.001). In the mother-baby and father-baby comparison, maternal BMI predicted neonatal fat (β = 0.20 SD; p < 0.001) and neonatal trunk+head (β = 0.15 SD; p = 0.001). Both maternal (β = 0.12 SD; p = 0.002) and paternal height (β = 0.09 SD; p = 0.030) predicted neonatal trunk+head but the associations became weak and statistically non-significant in multivariate analysis. Only paternal height predicted neonatal leg length (β = 0.15 SD; p = 0.003).ConclusionPrincipal components analysis is a useful method to describe neonatal body composition and its determinants. Newborn adiposity is related to maternal nutritional status and parity, while newborn length is genetically determined. Further research is needed to understand mechanisms linking maternal pelvic size to fetal growth and the determinants and implications of the components (trunk v leg length) of fetal skeletal growth.

Low Vitamin D Status in Mother-Newborn Pairs in Greece

Adequate vitamin D status during pregnancy is crucial to assure normal fetal skeletal growth and to provide the vitamin D needed for infants' stores. To determine the actual situation in Greece, we evaluated serum 25-hydroxyvitamin D (25[OH]D), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), osteocalcin (OC), and calcitonin (CT) concentrations in 123 healthy mother-newborn pairs recruited from a public hospital of the sunny Athenian region. Blood samples were obtained from pregnant women at term and their neonates (cord blood). The study was conducted between June 2003 and May 2004. None of the mothers has been prescribed vitamin D supplements. Maternal 25(OH)D levels (16.4 [11-21.1] ng/mL) were significantly lower than umbilical venous blood concentrations (20.4 [13.9-30.4] ng/mL) (P < 0.001). A strong correlation was observed between maternal and infant 25(OH)D concentrations (r = 0.626, P < 0.001). Twenty-four (19.5%) mothers and 10 (8.1%) neonates had 25(OH)D <10 ng/mL. Pregnant women who delivered in summer and autumn reported higher levels of 25(OH)D (18.9 [12.9-23.3] ng/mL) than those who delivered in winter and spring (14.6 [10.1-18.5] ng/mL) (P = 0.006). Mothers with a darker phototype had lower levels of serum 25(OH) D than those with a fair phototype (P = 0.023). Umbilical venous blood Ca, P, OC, and CT levels were significantly higher than maternal venous blood levels (P < 0.001). PTH umbilical levels were lower than maternal levels (P < 0.001). Apparently, the abundant sunlight exposure in Athens is not sufficient to prevent hypovitaminosis D. Pregnant women should be prescribed vitamin D supplementations, and the scientific community should consider vitamin D supplementation of foods.

Relationship between pregnancy outcomes and maternal vitamin D and calcium intake: A cross-sectional study

Poor maternal vitamin D status affects fetal and infant skeletal growth. The aim of the present study was to determine the association between newborn outcomes and maternal calcium and vitamin D intakes. Four hundred and forty-nine pregnant women, healthy at the point of delivery, and their newborns were enrolled in the study, which was performed in three university hospitals in Tehran in March 2004. Maternal anthropometric data and energy, protein, calcium and vitamin D intakes were collected, and newborn outcomes (weight, length, head circumference and 1-min Apgar score) were determined. Almost two-thirds of the mothers (64.3%) took no supplements during pregnancy. Only one-third of the mothers (33.8%) had adequate intakes of calcium and vitamin D (from supplements and foods) compared with the Recommended Dietary Allowances. Mean length at birth and 1-min Apgar score were higher in newborns whose mothers had adequate calcium and vitamin D intake than in newborns whose mothers had inadequate intake (p = 0.03 and p = 0.04, respectively). Significant correlations were found between adequate maternal calcium and vitamin D intake and both appropriate birth weight and 1-min Apgar score of newborns and weight gain of mothers during pregnancy. Informing mothers of the critical importance of consuming adequate amounts of calcium and vitamin D seems necessary.

Evidence of genetic regulation of fetal longitudinal growth

Background Genetic as well as environmental factors are important determinants of fetal growth but there have been few studies of the influence of paternal factors on fetal growth. Aim To study the influence of paternal anthropometry on detailed measurements of offspring at birth. Design A prospective cohort study involving biochemistry, and anthropometry, of mothers and fathers at 28 weeks gestation, and detailed anthropometry of children within 24 h of birth. Subjects 567 White Caucasian singleton, non-diabetic, full term pregnancies recruited from central Exeter, UK. Results Paternal height, but not paternal BMI, was correlated with birth weight ( r = 0.19) and with birth length ( r = 0.33). This was independent of potential confounders and maternal height. All measurements of fetal skeletal growth including crown–rump, knee–heel and head circumference were associated with paternal height. Maternal height showed similar correlations with birth weight ( r = 0.18) and birth length ( r = 0.26). Maternal BMI was correlated with birth weight ( r = 0.27) and birth length ( r = 0.15). In a multifactorial analysis 38% of the variance in fetal height could be explained by gestation, sex, paternal height, maternal height, maternal glucose, maternal BMI, parity and maternal smoking. Conclusion Paternal height has an independent influence on size at birth. This predominantly influences length and skeletal growth of the baby. In contrast to maternal obesity the degree of paternal obesity does not influence birth weight. This work suggests that there is genetic regulation of skeletal growth while the maternal environment predominantly alters the adiposity of the fetus.

The Effects of Pregnancy and Lactation on Bone Mineral Density

We performed a prospective study of bone mineral density (BMD) in 38 women during their first full-term pregnancy until 12 months postpartum. BMD measurements at lumbar spine [L2-L4 (LS)] and forearm [distal 33% (RD) and ultradistal (RUD) region of the radius] were made within 3 months before conception, after delivery, and at 6 and 12 months postpartum. In mid-pregnancy the DXA examination was carried out only at the forearm. Patients were grouped according to duration of lactation as group I, II or III (0-1, 1-6, 6-12 months respectively). During pregnancy there was a significant difference between baseline and delivery (p< 0.001) in the LS, RUD and RD BMD values. In group I there was no statistically significant difference in LS BMD between visits following pregnancy. The RUD BMD loss was recovered by 6 months postpartum (PP6). Group II showed continuous bone loss from delivery until PP6 at LS and RUD. In group III the LS BMD loss continued throughout the lactation period. The RUD BMD dropped (4.9%) until PP6 then increased by 3.0% as measured at 12 months postpartum (PP12). There was no significant change in RD BMD in any of three groups during lactation. At LS bone loss between delivery and PP12 correlated well with the duration of lactation (r = -0.727; p<0.001). We suggest that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients. The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning.

Intrauterine growth retardation due to growth hormone deficiency in rats.

The effect of growth hormone (GH) on fetal growth was examined in the spontaneous dwarf rat (SDR) with the isolated GH deficiency. A 328-bp GH gene fragment containing the site of SDR mutation was amplified from fetal liver genomic DNA using PCR and digested with restriction enzyme SauI to distinguish the fetal genotype. When heterozygote (dr/+) males and females were crossed, a significant reduction in body weight of dr/dr fetuses was observed on days 20 and 21 (92 and 89% that of +/+ fetuses, respectively). Body weight reduction was also noticed on day 21 in dr/dr fetuses (80%) in comparison with that of dr/+ fetuses crossed from dr/dr females and dr/+ males. Unexpectedly, the body weight of dr/+ fetuses was found to be significantly less than that of +/+ fetuses on days 19 (94%) and 20 (97%), which reached the level of +/+ fetuses by day 21 of gestation. The fetal tail length was not affected by the GH status. These results provide direct evidence for the involvement of pituitary GH in the regulation of fetal body weight during late gestation, but not in fetal skeletal growth.

Effect of Hypoinsulinemia on Growth in the Fetal Rabbit

Insulin is an important regulatory hormone in the control of fetal growth. In a fetal rabbit model, a non-ruminant species, the effects of insulin deprivation on glucose, growth and protein metabolism were studied. The fetuses of 10 pregnant New Zealand white rabbits in one uterine horn received a subcutaneous injection on day 25 of gestation (term = 30 days) of 0.1 mg streptozotocin (STZ)/gm fetal weight. The fetuses in the opposite horn received a sham injection of buffer. The dams were then killed on day 29. The fetal insulin concentration was depressed by 38%, and the serum glucose concentration was elevated by 28% in animals given STZ when compared to control animals. Fetal weights, carcass weights and skeletal growth, as measured by crown-rump length and tibial length of STZ-treated fetuses, were significantly reduced by 7-13%. However, organ weights were not significantly different, except for the kidneys which were 17% lighter. Protein and mineral contents of the carcasses were also reduced compared to the control fetuses. Thus, insulin deprivation in fetal rabbits results in significant growth impairment in a pattern similar to that of human asymmetric intrauterine growth retardation.

Temporal relationship between fetal bovine skeletal growth and circulating hormonal levels.

Skeletal growth and serum hormonal levels in bovine fetuses were studied cross-sectionally from late first trimester to late third trimester of gestation (corresponding approximately to 75-275 days of age, and a crown-rump (CR) 5-105 cm/in size). Measurements of tibial and femoral lengths showed that bone growth proceeds at a 30% faster rate in fetuses of 50-105 cm CR, coincident with the appearance and exponential growth (y = 0.000207 e 0.12522 x; y, dried weights of ossification in grams and x, CR in cm) of a secondary center of ossification in the epiphysis. During this period there is an increase in the proportion of [3H]-thymidine-labeled nuclei (measured by autoradiography) in the proliferative zone of the epiphyseal growth plate and a progressive hypertrophy of chondrocytes in the epiphysis; in serum there is a rise in alkaline phosphatase activity, a rise in the calcium, and a decrease in the phosphorus concentrations. Cellularity (nuclei/area) and the proportion of [3H]-thymidine labeled nuclei in epiphyseal cartilage decline during the period of 15-105 cm CR, except at 25-45 cm CR when both parameters of chondrocyte growth have transiently stabilized. [35S]-Sulfate and [3H]-proline incorporation (cpm/100 micrograms DNA) in epiphyseal cartilage also decline initially during 10-25 cm CR, then attain a stable level during 25-50 cm CR; subsequently, [35S]-sulfate incorporation gradually increases and [3H]-proline incorporation remains at a constant level. The proportion of [3H]-thymidine-labeled nuclei in the epiphyseal growth plate also declines in early gestation, then becomes stabilized at 20-50 cm CR. The whole growth plate thickness varies during gestation and is maximal during 20-50 cm CR. The proliferative zone attains maximal thickness at 20-50 cm CR while the hypertrophied and degenerative zone has maximal thickness at 40-80 cm CR. Gestational changes of hormone levels were quantitated in fetal serum. Glucocorticoids and thyroxine were measured by radioimmunoassay; somatomedinlike bioactivity was measured as the capacity of a serum sample to stimulate [3H]-thymidine incorporation in chondrocytes compared to that of a control serum. Temporally related to the changes occurring in the skeletal tissues, there is a high serum level of glucocorticoids at 10-20 cm CR when the cartilaginous activities are declining, a peak level of serum somatomedinlike bioactivity at 20-50 cm CR when cartilage growth and metabolism become stabilized, and a rise of thyroxine level after 45 cm CR during which time there is an increasing rate of bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)

FAT, CALCIUM (Ca) AND MAGNESIUM (Mg) BALANCE IN PRETERM INFANTS (PI) FED HUMAN MILK (HM) OR LOW BIRTH WEIGHT FORMULA (LBWF) AT DIFFERENT POSTNATAL AGE

During the last trimester of pregnancy, the fetal skeletal growth requires a massive mineral transfer from mother to fetus. Interruption of this process favors the development of osteopenia in PI. We studied in 12 PI (BW : 1318 g ± 142; GA : 30.5 wks ± 1.5), 6 fed either HM or LBWF, fat absorption and Ca and Mg absorption and retention at 20-25 days (study 1) and 44-45 days (study II) after birth. HM was enriched in phosphate (9 mg/dl) and babies received 1500 I.U. vit.D/d. The results were (in mg/kg/day): *:p<0.05 These results showed : 1) Fat, Ca and Mg absorption were low in PI fed HM but increased with postnatal age. 2) In PI fed LBWF, fat absorption was normal, Ca and Mg retention was higher in both studies.

Fetal cartilage xylosyltransferase activity and skeletal growth in sheep.

The activity of UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC 2.4.2.26), the enzyme that catalyzes the initiation of the polysaccharide chain linkage to the core protein of proteoglycans, was measured in costal cartilage from 20 fetal sheep of 65-138 days gestation. Activity of the enzyme was estimated from the transfer of [14C]xylose from UDP-[14C]xylose to silk as the acceptor protein. The specific activity decreased approximately 10-fold and was found to be highly correlated with the decremental rate of growth in length of the fetal vertebral column. These observations, together with the known gestational decrease in the in vitro rate of uptake of radiolabeled sulfate by ovine fetal cartilage, a subsequent step in proteoglycan synthesis, support the hypothesis that normal fetal skeletal growth is dependent during the last one-half of gestation on the activity of xylosyltransferase in cartilage.

INCREASED UPTAKE OF SO4 BY CARTILAGE OF FETAL SHEEP PERFUSED WITH SO4 COMPARED TO THEIR TWINS

Top of pageAbstract To test the hypothesis that fetal skeletal growth decreases in late gestation because the reported decline in serum sulfate conc ([SO4]) limits SO4 for incorporation into glycosaminoglycans by cartilage, 6 fetal sheep were perfused with Na2SO4 2.2 g/h i.v. for 7 d. As controls, the twin of each fetus was perfused with equimolar NaCl. Costal cartilage was harvested at GA=134 d and assayed in vitro for 35SO4 uptake (QSO4, μ g/24h/mg cartilage adjusted per mg SO4/tube) in the presence of 0, 10% and 20% normal human serum (NHS). Sera sampled before and during perfusion were assayed for [SO4]. Pairwise comparison of twin fetuses reveals SO4-perfusion produces a 34-47% increase in QSO4 independent of [NHS], compared to the ~300% increase in QSO4 produced by 20% NHS. Fetal wt, length, and sex were not different between groups. These results demonstrate that although late fetal cartilage in vitro QSO4 may be increased by elevating the fetal serum [SO4], other serum factors are more important determinants of fetal cartilage metabolic activity. The decrease in [SO4] observed from mid-gestation to term likely represents depletion of the SO4 pool by fetal growth processes rather than a decreased availability of SO4 that restricts growth.

Somatomedin production in the neonatal rat.

The hormonal stimulus to rat fetal and neonatal somatic and skeletal growth has been investigated by a study of ciruclating somatomedin (SM), growth hormone (GH) and insulin levels in rats from 21 days in utero to 40 days of post natal life. Somatomedin activity could not be detected in the serum of fetal rats in which circulating GH and insulin levels were high. In early post natal life GH and insulin levels remained high but gradually declined reaching normal adult levels at 19 days and 40 days respectively. Somatomedin activity was measurable only at low levels until 11 days after birth and thereafter remained steady throughout the time period studied. These studies suggest that somatomedin alone is not responsible for the rapid growth of the rat in early neonatal life and it is suggested that insulin may also be active as a growth factor in this period.

MOVEMENT OF CALCIUM IN BOTH DIRECTIONS ACROSS THE PRIMATE PLACENTA.

SummaryTransfer of Ca from mother to fetus concurrent with transfer from fetus to mother was studied in 3 pregnant rhesus monkeys. Ca45 was injected into a fetal inter-placental vessel simultaneously with intravenous injection of Ca47 into the anesthetized mother. Samples of maternal blood (MB), fetal blood (FB), and amniotic fluid (AF) were assayed for Ca45, Ca47 and non-radioactive Ca. Initial loss of Ca47 from MB was matched by rapid initial appearance in FB (t 1/2 ≤ 6 min) and somewhat slower entry into AF. Similarly, Ca45 appeared in MB at a rate almost equal to the initial rate of loss from FB. The quantity of Ca crossing the placenta daily was at least 6–10 times that required for fetal skeletal growth.