National curves of foetal growth in singleton foetuses of Greek origin.

BACKGROUND: Foetal growth monitoring is an essential component of prenatal care with postnatal impact. The aim of the study was to construct reference ranges for foetal biometric parameters in Greek foetuses and to compare them with previously published models. MATERIALS AND METHODS: Measurements from 1200 Greek foetuses were used to construct normal curves for biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC), abdominal circumference (AC), femoral length (FL) and the BPD/FL ratio according to the methodology described by Royston and Wright (1998). The model was validated in a second group of 1200 different foetuses using analysis of the corresponding standardized residuals (z-scores). The z-scores which were derived by our model were compared to those calculated using previously published models from other populations. RESULTS: BPD, OFD, HC, AC, FL and the BPD/FL ratio are accurately described by simple quadratic equations (R(2) > 0·96 for most of the parameters tested). Statistically significant differences were observed for most of the z-scores when our models were compared to previously published models. Less than 10% of our foetuses were < 5th or > 95th centile of the latter models. About 10% of our foetuses were > 95th centile for FL and HC when the INTERGROWTH-21st formulas were used. CONCLUSION: We present national foetal biometric references. Using charts from other populations (including INTERGROWTH-21st) may be unrepresentative of local populations and lead to misclassification of foetal growth status.

Maternal serum osteocalcin at 11-14 weeks of gestation in gestational diabetes mellitus.

BACKGROUND: Recent studies support that osteocalcin (OC), apart from its skeletal role, is implicated in glucose homoeostasis. Aims of this study were to examine the first-trimester maternal serum concentrations of OC in pregnancies that developed gestational diabetes mellitus (GDM) and to create a first-trimester prediction model for GDM. DESIGN: Case-control study in a prospective cohort of pregnant women. Maternal serum levels of OC were measured in 40 cases that developed GDM and 94 unaffected controls. First-trimester biophysical parameters, biochemical indices, maternal-pregnancy characteristics, and OC concentrations were assessed in relation to GDM occurrence. RESULTS: In the GDM group, first-trimester OC serum levels were increased compared to the control group (mean = 8·81 ng/mL, SD = 2·59 vs. mean = 7·34 ng/ml, SD = 3·04, P = 0·0058). Osteocalcin was independent of first-trimester biophysical and biochemical indices. Osteocalcin alone (OR = 1·21, CI: 1·02-1·43, P = 0·023) was a significant predictor of GDM [Model R(2) = 0·04, area under the curve (AUC) = 0·61, CI: 0·55-0·72, P < 0·001]. The combination of maternal and pregnancy characteristics with OC resulted in an improved prediction model for GDM (Model R(2) = 0·21, AUC = 0·80, CI: 0·71-0·88, P < 0·001). The combined model yields a sensitivity of 72·2% for 25% false-positive rate. CONCLUSIONS: First-trimester maternal serum levels of OC are increased in GDM pregnancies. Osteocalcin combined with maternal and pregnancy characteristics provides an effective screening for GDM at 11-14 weeks.

Cord blood galectin-1 and -3 concentrations in term pregnancies with normal restricted and increased fetal growth.

OBJECTIVE: To determine levels of galectins (gal)-1 and -3 (implicated in angiogenesis/immunologic mechanisms) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies, as these groups differ in fat mass, angiogenic patterns and immune responses. METHODS: Cord-blood (UC) gal-1 and -3 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA singleton full-term infants and their mothers (MS). RESULTS: IUGR, LGA and AGA groups did not differ in gal-1 and -3 concentrations. UC gal-1 levels were lower when mothers were older [b=-0.651, CI 95% -1.186 (-0.116), P=0.018] and UC gal-3 levels were increased when mothers presented gestational diabetes [b=9.836, CI 95% 3.833- (15.839), P=0.002]. In IUGRs MS gal-3 and in LGAs UC gal-1 were decreased in multiparas [b=-5.372, CI 95% -9.584- (-1.161), P=0.014], and [b=-7.540, CI 95% -14.606- (-0.473), P=0.037], respectively. No correlations were found between MS or UC gal-1 and gal-3 concentrations. CONCLUSIONS: Lower UC gal-1 levels, when mothers were older, and increased UC gal-3 levels in cases of gestational diabetes, possibly reflect angiogenic activity. In multiparas, decreased MS gal-3 and UC gal-1 levels in IUGR/LGA, respectively, might imply inflammatory response against immunosuppression expected in subsequent pregnancies, as compared to the first one.

Maternal serum levels of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study.

BACKGROUND: The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and MMP-9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA). METHODS: Neutrophil gelatinase-associated lipocalin, MMP-9, and MMP-9/NGAL were determined in the first, second, and third trimesters in 33 normal pregnancies, 12 pregnancies complicated by preeclampsia, and 14 pregnancies that delivered a SGA neonate. RESULTS: Median NGAL concentration (ng/mL) in normal pregnancies increased significantly from 12.8 in the first trimester to 25.9 in the second trimester (p = 0,002) and 48.0 (p < 0.0001) in the third trimester. In preeclamptic pregnancies, NGAL was significantly higher, compared with normal pregnancies, in the first (30.9; p = 0.006) and second (44.6; p = 0.015) trimesters. MMP-9 and MMP-9/NGAL complex concentrations in preeclamptic pregnancies did not differ significantly from normal pregnancies in either trimester. Pregnancies with an SGA infant did not have different marker concentrations in either trimester, compared with normal pregnancies. CONCLUSION: Maternal serum NGAL, MMP-9, and MMP-9/NGAL complex concentrations tend to increase during pregnancy in normal and preeclamptic pregnancies. NGAL was significantly elevated in the first and second trimesters, in pregnancies that later developed preeclampsia.

Adipokines vaspin and omentin-1 are up-regulated in large for gestational age infants at term.

OBJECTIVE: Large- (LGA) and appropriate-for-gestational age (AGA) infants differ in body fat mass and metabolic/endocrine mechanisms. We aimed to investigate in LGA and AGA infants possible alterations in cord blood levels of insulin and the adipokines vaspin and omentin-1 which are secreted by the adipose tissue and are implicated in insulin resistance/metabolic syndrome. METHODS: Cord blood vaspin, omentin-1 and insulin levels were prospectively measured in 61 LGA and 36 AGA singleton full-term infants. Of the LGA group 13 infants were born from diabetic and 48 from non-diabetic mothers. RESULTS: Cord blood vaspin and omentin-1 levels were significantly higher in LGA compared with AGA neonates (p = 0.021 and b = 0.115, SE 0.037, p = 0.002, respectively). Umbilical cord omentin-1 levels were significantly decreased in neonates delivered vaginally (b = -0.075, SE 0.031, p = 0.016), after controlling for group. Insulin levels increased in proportion to the customized centiles of the infants (b = 0.004, SE = 0.001, p = 0.009). Finally, in the LGA group vaspin levels correlated with omentin-1 serum levels (r = 0.318, p = 0.013). CONCLUSIONS: The increased levels of vaspin observed in LGA infants compared with AGA ones, possibly represent a defensive mechanism against insulin/glucose dysregulation, commonly seen in the former. In addition, the increased omentin-1 levels in the LGA group could possibly reflect the amount of developing adipose tissue in the early stages of life in this group. Alternatively, these levels could reflect the growth-promoting effect of omentin-1 in the fetus. The inflammation associated with vaginal deliveries may account for the lower cord blood omentin-1 levels in neonates delivered by this mode.

Cord blood nesfatin-1 in large for gestational age pregnancies.

OBJECTIVE: To investigate possible alterations in cord blood levels of adipokine nesfatin-1 (secreted by adipose tissue and pancreatic ß-cells and implicated in glucose metabolism and insulin resistance), as well as insulin, in large (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms. MATERIALS AND METHODS: Cord blood nesfatin-1 and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from non-diabetic mothers) and 20 AGA singleton full-term infants as well as their mothers. RESULTS: Cord blood nesfatin-1 concentrations were significantly lower in LGA compared to AGA neonates (b=-0.206, SE 0.07, p=0.005). However, cord blood nesfatin-1 concentrations were elevated in infants born from mothers with gestational diabetes mellitus (GDM), compared to those born from non-diabetic mothers, after controlling for group (b=0.190, SE 0.10, p=0.05). Finally, cord blood nesfatin-1 concentrations were lower in cases of vaginal delivery (b=0.11, SE 0.05, p=0.042). Insulin levels were significantly elevated, as customized centiles increased (b=0.004, SE=0.002, p=0.016). No significant correlation was found between insulin and nesfatin-1 in maternal and umbilical cord levels. CONCLUSIONS: In this study nesfatin-1 levels are decreased in LGA compared to AGA fetuses. Fetal nesfatin-1 concentrations are higher in cases of GDM and cord blood nesfatin-1 concentrations are lower in cases of vaginal delivery.

Circulating levels of inflammatory markers in intrauterine growth restriction.

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B--probably reflecting brain and adipose tissue inflammation--in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates--despite the lower birth weight, reflecting reduced fat mass in the former--might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded.

Cord blood ischemia-modified albumin levels in normal and intrauterine growth restricted pregnancies.

Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals--"brain sparing effect"). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, "brain sparing effect" is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

Intrauterine growth restriction and circulating neurotrophin levels at term.

BACKGROUND: Intrauterine growth restricted (IUGR) fetuses are those with estimated weight <10th customized centile, displaying signs of chronic malnutrition and hypoxia leading to brain sparing effect. Neurotrophins, [Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), Neurotrophin-4 (NT-4)] are important for pre- and post-natal brain development. AIMS: To investigate circulating NGF, BDNF, NT-3 and NT-4 levels in IUGR and appropriate for gestational age (AGA) fullterm fetuses and neonates (day-1 [N1] and day-4 [N4]) and in their mothers. STUDY DESIGN: Prospective case control study. SUBJECTS: 60 mothers and their single 30 IUGR and 30 AGA fullterm fetuses and neonates. OUTCOME MEASURES: Determination, by enzyme immunoassays, of NGF, BDNF, NT-3 and NT-4 plasma levels. RESULTS: No statistically significant differences existed between IUGR and AGA maternal, fetal and neonatal levels of BDNF, NT-3 and NT-4. NGF was significantly higher in AGA than IUGR maternal (p=0.007), fetal (p=0.01), neonatal day 1 (p=0.043) and 4 (p=0.003) plasma, and positively correlated with the infants' centiles and birthweights. IUGR and AGA maternal neurotrophins were higher than the respective fetal and neonatal ones and no correlation with gender or delivery mode in both groups was observed. CONCLUSIONS: In the perinatal period, circulating levels of BDNF, NT-3 and NT-4 do not differ in IUGR and AGA pregnancies, in contrast to NGF levels, which are higher in the AGA group. NGF is the only neurotrophin correlating with customized centiles and birthweights of the infants. Neurotrophin concentrations are higher in maternal plasma and do not depend on gender.

Perinatal changes of circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) in normal and intrauterine-growth-restricted pregnancies.

OBJECTIVE: To investigate changes in NT-proBNP in intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) pregnancies. METHODS: NT-proBNP levels were measured in 40 mothers (MS), umbilical cords (UC), and their 20 IUGR/ 20 AGA neonates on day 1 (N1) and day 4 (N4). RESULTS: UC, N1, and N4 NT-proBNP was lower in IUGR pregnancies (p

Perinatal changes of cardiac troponin-I in normal and intrauterine growth-restricted pregnancies.

Intrauterine growth restriction (IUGR) implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart). Serum cardiac Troponin-I (cTnI), a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state), and their 20 IUGR and 20 appropriate-for-gestational-age (AGA) neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r > or = .498, P < or = .025 in all cases in the AGA and r > or = .615, P < or = .009 in all cases in the IUGR group). These results may indicate (a) normal heart function, due to heart sparing, in the IUGR group (b) potential crossing of the placental barrier by cTnI in both groups.

Endometrioid adenocarcinoma arising from colon endometriosis.

Endometriosis-associated intestinal tumors represent the malignant transformation of gastrointestinal endometriosis. Approximately 50 cases have been reported in the literature. They are most commonly found among women aged 30-60 years, whereas exogenous hormone therapy and obesity are primary risk factors for the malignant transformation of endometriotic lesions. Clinical features simulate a primary colonic carcinoma. A high index of suspicion in conjunction with careful histological and immunohistochemical examination (CK7, CK20, CDX2, CD10, ER, and PR) is important for establishing a correct diagnosis. In this article, a rare case of a postmenopausal woman with no risk factors and conflicting clinical presentation, diagnosed with endometriosis-associated intestinal tumor, is described.

The role of the anti-angiogenic factor endostatin in intrauterine growth restriction.

OBJECTIVE: To study the impact of intrauterine growth restriction (IUGR) on anti-angiogenesis, by determining and comparing circulating levels of the potent anti-angiogenic factor endostatin, in full-term IUGR (under the 10th customized centile) and appropriate for gestational age (AGA) fetuses, neonates, as well as their mothers, granted that IUGR implies hypoxia and endostatin is down-regulated by the latter. METHODS: In 20 IUGR cases (mainly due to hypertension or preeclampsia) and 20 AGA controls we determined circulating endostatin levels, by enzyme immunoassay in the serum of mothers (MS), umbilical cords (UC-mixed arteriovenous blood)-representing the fetal state, and asymptomatic neonates on day 1 (N1) and 4 (N4) of life-signifying transition and stabilization to extrauterine life, respectively. RESULTS: Endostatin levels were significantly higher in AGA than IUGR UC, N1, and N4 (P <.0000, P = .0006, P = .024, respectively). Furthermore, UC endostatin levels positively correlated with the customized centiles of the infants (Spearman correlation coefficient 0.69, P = .00001). CONCLUSIONS: IUGR is characterized by lower circulating endostatin concentrations in the fetus and neonate, possibly because under lower oxygen concentrations an unbalanced state of angiogenesis stimulators versus inhibitors takes place.

Elevated placental growth factor concentrations at 11-14 weeks of gestation to predict gestational diabetes mellitus.

OBJECTIVE: To examine maternal serum concentrations of placental growth factor (PlGF) at 11-14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. METHODS: Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal-pregnancy characteristics were analyzed. RESULTS: Log10 transformed PlGF (log10 PlGF) was not related to maternal factors. Log10 PlGF was increased (p=0.008) in the GDM group compared to the control group. Log10 PlGF was associated with fasting glucose levels (p=0.04) in the oral glucose tolerance test. Log10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC)=0.73, p<0.001]. Log10 PlGF alone was a significant predictor of GDM (AUC=0.63, p<0.001). Combination of maternal weight, maternal age and log10 PlGF resulted in an improved prediction (DR=71.4%, for 25% FPR, AUC=0.78, Model R(2)=0.17, p<0.001). CONCLUSION: At 11-14weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11-14weeks improves the performance of early screening for GDM provided by maternal factors alone.

Cord blood netrin-1 and -4 concentrations in term pregnancies with normal, restricted and increased fetal growth.

OBJECTIVE: To determine levels of the possible angioregulatory molecules netrin-1 and -4, in intrauterine-growth-restricted (IUGR), large for gestational age (LGA) (both groups characterized by altered angiogenic mechanisms) and appropriate-for-gestational-age (AGA) pregnancies. METHODS: Cord blood (UC) netrin-1 and -4 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA infants and their mothers (MS). RESULTS: Netrin-1 and -4 concentrations did not differ in all groups. UC netrin-4 increased with gestational age (b = 0.075, 95% CI 0.029-0.121, p = 0.002). In the IUGR group, MS netrin-4 decreased as birth-weight centiles increased [b = -0.058, 95% CI -0.112 to -0.004, p = 0.036]. In the LGA group, MS netrin-1 decreased with advanced gestational age [b = -0.063, 95% CI -0.105 to -0.022, p = 0.004]. In all cases, MS netrin-1 positively correlated with MS netrin-4 (r = 0.299, p = 0.007), while UC netrin-1 negatively correlated with UC netrin-4 (r = -0.239, p = 0.033). CONCLUSIONS: Increased UC netrin-4 levels with advancing gestational age may reflect its effect on fetal development. Decreased maternal netrin-1 levels in the LGA group possibly represent a negative feedback mechanism against increased angiogenesis. Increased maternal netrin-4 levels in IUGR neonates may reflect in utero hypoxia, while the negative correlations between fetal netrin-1 and -4 levels may exert the dynamic balance between their angio- and anti-angiogenic properties.

Cord blood chemerin and obestatin levels in large for gestational age infants.

OBJECTIVE: To investigate possible alterations in cord blood levels of adipokines, chemerin and obestatin (secreted by adipose tissue and associated with later development of insulin resistance/metabolic syndrome), as well as insulin, in large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms. METHODS: Cord blood chemerin, obestatin, and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from nondiabetic mothers) and 40 AGA singleton full-term infants. RESULTS: Cord blood chemerin concentrations were significantly higher in LGA compared with AGA neonates (b = 38.91, SE 9.29, p < 0.001). In contrast, no significant differences in obestatin concentrations were observed between groups. Insulin levels were significantly elevated as customized centiles increased (b = 0.003, SE = 0.001, p = 0.032). CONCLUSIONS: Higher chemerin concentrations in LGA neonates possibly reflect the increased adipose tissue in this group. Lack of difference between the two groups in circulating levels of obestatin-possibly a sensitive marker of insulin resistance-might be due to development of metabolic disorders later in life.

Detection of congenital heart defects throughout pregnancy; impact of first trimester ultrasound screening for cardiac abnormalities.

OBJECTIVE: To evaluate prospectively the efficacy to screen for congenital heart defects (CHD) during the first trimester nuchal translucency (NT) ultrasound examination by assessing the four chambers' view of fetal heart. METHODS: Pregnancies that were examined prospectively by ultrasound in the first trimester (11th-14th week), the second (19th-24th week) and third trimester were included in the study. 3774 fetuses were examined and fetal heart was assessed during the NT scan by examining the four chambers view. Detailed echocardiography was performed during the anomaly and growth scans. Diagnosis of congenital heart defects (CHD) was further confirmed by a fetal cardiologist. RESULTS: The four chambers view was obtained in 99.52% of the cases. CHD were diagnosed in 29 fetuses (0.77%). Thirteen cases (44.8%) were detected during the 11-13 weeks' scan, 14 cases (48.3%) during the anomaly scan, 1 CHD (3.5%) during the third trimester scan and 1 case (3.5%) postpartum. CONCLUSION: Assessment of the four chambers of fetal heart early in pregnancy was feasible and allowed the detection of 45% of CHD. Additional parameters of fetal cardiac anatomy during the NT scan may further improve the detection rate providing pregnancy management information early in the first trimester.

Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby.

OBJECTIVE: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. METHODS: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. RESULTS: Mean (±SD) concentrations of ADMA (µmol/L) in uncomplicated l pregnancies were: 0.51 ± 0.14; 0.52 ± 0.13; 0.58 ± 0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40 ± 0.10, p = 0.005 1st trim; 0.42 ± 0.10, p = 0.007 2nd trim; 0.45 ± 0.10, p = 0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58 ± 0.10; 0.63 ± 0.14; 0.68 ± 0.11), the difference was statistically significant only in the 2nd trimester (p = 0.02). CONCLUSIONS: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia.

Perinatal collagen turnover markers in intrauterine growth restriction.

OBJECTIVE: To investigate bone and connective tissue collagen turnover in intrauterine growth restricted (IUGR) pregnancies, by determining circulating markers of type I collagen synthesis (carboxy-terminal propeptide of type I procollagen [PICP], representing bone formation) and degradation (cross-linked telopeptide of type I collagen [ICTP], representing bone resorption) as well as type III collagen synthesis (N-terminal propeptide of type-III procollagen [PIIINP], reflecting growth and tissue maturity). METHODS: Plasma PICP, ICTP and PIIINP concentrations were measured in 40 mothers and their 20 asymmetric IUGR and 20 appropriate for gestational age (AGA) full-term fetuses and neonates on postnatal day 1-(N1) and 4-(N4). RESULTS: Fetal PICP, fetal and N4 ICTP, as well as fetal, N1 and N4 PIIINP concentrations were higher in the IUGR group (p ≤ 0.038, in all cases). In both groups, maternal PICP, ICTP and PIIINP concentrations were lower than fetal, N1 and N4 ones (p<0.001, in each case). CONCLUSIONS: Type I collagen turnover is enhanced in IUGR than AGA fetuses/neonates. Similarly, fetal/neonatal PIIINP concentrations are elevated in IUGR, probably due to stress, responsible for induction of tissue maturation, and/or to impaired excretory renal function, leading to reduced protein clearance. Fetal/neonatal PICP, ICTP and PIIINP concentrations are higher than maternal concentrations, possibly reflecting increased skeletal growth and collagen turnover in the former.

Circulating osteoprotegerin and sRANKL concentrations in the perinatal period at term. The impact of intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) has been associated with low bone mass in infancy and increased risk for osteoporosis development in adult life. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are main determinants of bone resorption. OBJECTIVES: To investigate OPG and soluble RANKL (sRANKL) concentrations in maternal, fetal and neonatal serum of IUGR patients and appropriate for gestational age (AGA) pregnancies. Additionally, plasma intact parathormone (PTH) concentrations were evaluated. METHODS: Circulating OPG, sRANKL and PTH concentrations were measured in 40 mothers and their singleton full-term fetuses-neonates (AGA: n = 20, and IUGR: n =20) on postnatal days 1 (N1) and 4 (N4). RESULTS: No significant differences in OPG, sRANKL or PTH concentrations were observed between AGA and IUGR groups. In both groups, maternal OPG concentrations were elevated compared with fetal, and N1 and N4 concentrations (p < or = 0.045 in all cases). N4 sRANKL concentrations were elevated compared with maternal, fetal and N1 ones (p < or = 0.01 in all cases). Fetal and N1 sRANKL concentrations correlated positively with PTH levels (r = 0.642, p = 0.024 and r = 0.584, p = 0.046, respectively). CONCLUSIONS: The lack of a difference in circulating OPG, sRANKL or PTH concentrations between IUGR cases and AGA controls suggests that the low bone mass of IUGR infants may not be related to higher bone resorption rates. The increased maternal, compared with fetal/neonatal, OPG concentrations may suggest their placental origin. The lower OPG and higher sRANKL concentrations in fetuses and neonates could represent high bone resorption rates.