Maternal vitamin D status affects bone growth in early childhood--a prospective cohort study.

UNLABELLED: In this prospective study, 87 children were followed up from birth to 14 months with data on maternal vitamin D status during the pregnancy. Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. INTRODUCTION: Intrauterine nutritional deficits may have permanent consequences despite improved nutritional status postnatally. We evaluated the role of prenatal and postnatal vitamin D status on bone parameters in early infancy. METHODS: Eighty-seven children were followed from birth to 14 months. Background data were collected with a questionnaire and a 3-day food record. At 14 months bone variables were measured with peripheral computed tomography (pQCT) from the left tibia. Serum 25-OHD and bone turnover markers were determined. Findings were compared with maternal vitamin D status during pregnancy. RESULTS: The children were divided into two groups based on vitamin D status during pregnancy. Despite discrepant S-25-OHD at baseline (median 36.3 vs. 52.5 nmol/l, p < 0.001), the values at 14 months were similar (63 vs. 66 nmol/l, p = 0.58) in Low D and High D. Serum 25-OHD increased more in Low D (p < 0.001) despite similar total intake of vitamin D (mean 12.3 µg/day). In Low D, tibial bone mineral content (BMC) was lower at birth but BMC gain was greater (multivariate analysis of variance [MANOVA]; p = 0.032) resulting in similar BMC at 14 months in the two groups. In High D, tibial total bone cross-sectional area was higher at baseline; the difference persisted at 14 months (MANOVA; p = 0.068). Bone mineral density (BMD) and ΔBMD were similar in the two groups. CONCLUSIONS: Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. Further attention should be paid to improving vitamin D status during pregnancy.

Heart rate and blood pressure control in infants exposed to maternal cigarette smoking.

AIM: Exposure to maternal cigarette smoking is a major risk factor for sudden infant death syndrome (SIDS). Foetal and postnatal smoke-exposure may alter cardiovascular control in infants. We studied heart rate (HR) and blood pressure (BP) responses in smoke-exposed infants. METHODS: Eleven infants exposed to maternal cigarette smoking were studied at the age of 12 +/- 2.1 (range 10-16) weeks. Twenty healthy, age-matched infants from non-smoking families served as controls. During confirmed slow-wave sleep (NREM3), 3-5 sec side motion and 45 sec 45 degrees head-up tilt tests were performed. RESULTS: Control infants showed consistent biphasic HR and BP responses to side motion, with an initial 2-5% increase followed by a 2% decrease (p < 0.0001). In smoke-exposed infants, the initial HR (p = 0.009) and BP responses (p < 0.0001) were markedly reduced, and the subsequent decrease in BP was more prominent (systolic blood pressure, SBP, p = 0.005; diastolic blood pressure, DBP, p = 0.03). No differences were observed between the groups in tilt test results, HR variability or HR responses to spontaneous arousals. CONCLUSION: Maternal cigarette smoking may alter vestibulo-mediated cardiovascular control in early infancy. This may contribute to increased SIDS risk.

Markers of collagen metabolism and insulin-like growth factor binding protein-1 in term infants.

AIM: To study the relation between fetal growth and markers of collagen metabolism and insulin-like growth factor binding protein-1 (IGFBP-1) in term infants. METHODS: Cord vein plasma was obtained from 67 term infants of gestational age 37.1-41.7 weeks (39 appropriate for gestational age (AGA), 11 large for gestational age (LGA; relative birth weight >/= 2.0 SD), and 17 small for gestational age (SGA; relative birth weight 0.05). CONCLUSIONS: In the term fetus, collagen metabolism is primarily dependent on maturity and not on intrauterine growth status, whereas IGFBP-1 reflects intrauterine growth independently of maturity.

Increased leptin concentration in preterm infants of pre-eclamptic mothers.

AIM: To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants. METHODS: Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids. RESULTS: The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) microg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids. CONCLUSIONS: Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.

Postnatal changes in concentrations of free and bound leptin.

AIM: To evaluate the effect of maternal diabetes on the concentrations of free and bound leptin at birth and during postnatal adaptation. METHODS: Total, bound, and free leptin concentrations and the percentage of free leptin were measured in cord plasma and plasma at 3 days of age of 13 term infants of mothers with gestational diabetes mellitus (GDM) and 13 term infants of healthy mothers. Gestational age was 40.2 (1.4) weeks, and birth weight was 3693 (549) g (means (SD)). RESULTS: At birth, infants of mothers with GDM had significantly higher concentrations of total, bound, and free leptin and a higher percentage of free leptin (all p < 0.05). In all infants, these concentrations were significantly lower at 3 days of age than at birth (all p < 0.003), and the differences in concentrations of total, bound, and free leptin between the two groups were no longer significant. In infants of mothers with GDM, the percentage of free leptin remained unchanged, and was higher (p<0.05) than in infants of healthy mothers; in the latter group the percentage of free leptin significantly declined (p = 0.02). CONCLUSIONS: GDM appears to influence fetoplacental leptin metabolism. This effect may be mediated through altered maternal glucose metabolism, or insulinaemia, or both.

Maternal vitamin D status determines bone variables in the newborn.

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.

Changes in leptin concentration during the early postnatal period: adjustment to extrauterine life?

There are substantial alterations in fuel homeostasis immediately after birth. Leptin is a putative regulator of energy metabolism. Consequently, the aim of this study was to examine whether there are changes in circulating leptin concentrations during the early postnatal period. Umbilical cord mixed blood samples were taken at delivery, and a venous blood sample was obtained at 3 d of age from 38 healthy newborn infants (20 male, 18 female; gestational age 36.3 to 41.9 wk) for analysis of leptin concentration with radioimmunoassay. Cord plasma leptin concentration was 9.7+/-5.2 microg/L (mean+/-SD), with no gender difference between male (8.6+/-4.6 microg/L) and female (10.9+/-5.6 microg/L) infants. In male newborns, cord plasma leptin concentration correlated with arm circumference (r = 0.48, p < 0.05), and in female newborns with body mass index (r = 0.62, p < 0.01), thickness of the s.c. fat (r = 0.54, p < 0.05), and arm circumference (r = 0.72, p < 0.01). By the third postnatal day, plasma leptin decreased similarly in male (to 1.8+/-0.4 microg/L, p < 0.001) and female (to 2.3+/-0.8 microg/L, p < 0.001) infants, when there was a significant gender difference in leptin levels (p = 0.01). At 3 d of age, plasma leptin correlated with weight (r = 0.49, p < 0.05) and arm circumference (r = 0.49, p < 0.05) in female but not in male newborns. In conclusion, 1) circulating leptin already correlates with adiposity at birth in female but not in male newborn infants and 2) leptin decreases markedly in both genders by the third postnatal day, and the gender difference with higher leptin levels in females develops by that time. Thus, the postnatal decrease in plasma leptin concentration may be a physiologically feasible adaptation to profound alterations in fuel homeostasis during the first days of extrauterine life.

Markers of type I and type III collagen turnover, insulin-like growth factors, and their binding proteins in cord plasma of small premature infants: relationships with fetal growth, gestational age, preeclampsia, and antenatal glucocorticoid treatment.

Disorders affecting fetal growth are commonly associated with premature birth. IGFs and their binding proteins (IGFBPs) are potent regulators of fetal growth. In vitro evidence suggests that they regulate collagen turnover. Collagen turnover can be monitored by serum markers of type I collagen synthesis (PINP) and degradation (ICTP) and a marker of type III collagen synthesis (PIIINP). We examined whether these markers in fetal circulation reflect intrauterine growth and maturity, and whether any interrelationship exists between them and fetal IGFs and IGFBPs in preterm infants before 32 wk of gestation. Cord plasma PINP, ICTP, PIIINP, IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were determined for 98 preterm infants. To express birth weight in units adjusted for gestational age, a birth weight SD score (SDS) was calculated. Negative correlations existed between gestational age and PINP (r = -0.43; p < 0.0001), ICTP (r = -0.34; p = 0.002), and PIIINP (r = -0.34; p = 0.0001). Positive correlations existed between birth weight SDS and PINP (r = 0.40; p = 0.0002) and ICTP (r = 0.48; p < 0.0001) but not PIIINP. Moreover, birth weight SDS was positively correlated with IGF-I (r = 0.58; p < 0.0001) and IGFBP-3 (r = 0.44; p < 0.0001) and negatively correlated with IGF-II (r = -0.36; p = 0.003) and IGFBP-1 (r = -0.50; p < 0.0001). Gestational age correlated with IGFBP-3 (r = 0.25; p = 0.03). In preeclampsia, IGF-I was lower (p = 0.002) and IGFBP-1 higher (p < 0.0001), also after adjustment for fetal size. The number of antenatal glucocorticoid treatments was associated with lower ICTP (p = 0.04), higher IGF-I (p = 0.002), lower IGF-II (p = 0.02), lower IGFBP-1 (p = 0.05), and higher IGFBP-3 (p = 0.004), also after adjustment for potential confounders. In multiple regression analysis, the factors significantly associated with PINP (R:(2) = 0.47) were gestational age and IGF-I, and those associated with ICTP (R:(2) = 0.54) were IGF-I, gestational age, and antenatal glucocorticoid treatment. We conclude that IGF-I may be involved in regulation of type I collagen turnover in the growing fetus. Cord blood PINP and ICTP reflect both fetal growth and maturity and deserve evaluation as potential indicators of postnatal growth velocity in preterm infants, whereas PIIINP reflects fetal maturity.

Increased fetal leptin in type I diabetes mellitus pregnancies complicated by chronic hypoxia.

AIMS/HYPOTHESIS: The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus. METHODS: We measured leptin and erythropoietin concentrations in cord plasma and amniotic fluid with radioimmunoassay in 25 pregnancies (gestational age 37.2 +/- 1.0 weeks). Fetuses with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as non-hypoxic. RESULTS: The hypoxic fetuses had significantly higher cord leptin concentrations than non-hypoxic fetuses (median 36.8; range, 12.5-135.1 vs median 16.2; range, 3.7-52.2 micrograms/l), (p = 0.0066). Cord plasma leptin (n = 25) correlated directly with amniotic fluid erythropoietin (r = 0.727, p = 0.0001), with cord plasma erythropoietin (r = 0.644, p = 0.0005) and with the maternal last trimester HbA1C (r = 0.612, p = 0.0019) and negatively with cord artery pO2 (r = -0.440, p = 0.032), and pH (r = -0.414, p = 0.040). CONCLUSION/INTERPRETATION: Fetal leptin concentrations increased concomitantly with erythropoietin during chronic or subchronic hypoxia. This phenomenon could indicate a role for leptin in fetal adaptation to hypoxia.

Fetal shoulder measurements by fast and ultrafast MRI techniques.

The purpose of this study was to evaluate magnetic resonance imaging (MRI) of fetal shoulder measurements of fetuses with suspected macrosomia. The actual fetal shoulder measurements made immediately after birth were compared with measurements obtained by fast and ultrafast MRI techniques antepartum. Eight singleton diabetic pregnant mothers underwent MRI examination with fast imaging in steady-state precession (TrueFISP) and spin-echo (SE) and gradient-echo (GE) echo-planar (EPI) sequences to show the fetal shoulder width. The actual shoulder width was measured immediately postpartum by a neonatologist. There was a statistically significant correlation between the MRI measurements and the actual shoulder width (P < 0.001 - P < 0.05) for all sequences. TrueFISP (r = 0.98, P < 0.001) was superior to EPI sequences (r = 0.88, P < 0.01 for SE EPI and r = 0.80, P < 0.05 for GE EPI). The images of all three sequences used were free of major motion artifacts. Fast and ultrafast sequences seem to be reliable for fetal shoulder measurements and the TrueFISP was the most accurate sequence compared to SE and GE echo-planar sequences. J. Magn. Reson. Imaging 2001;13:938-942.