Appropriate For Gestational Age Neonates Research Articles

PO-0422 Evaluation Of Cerebral Perfusion In Small For Gestational Age Neonates In The First Postnatal Week Using Colour Doppler Sonography

Background and aims Small for gestational age neonates (SGA) living in conditions of chronic hypoxia during fetal life may develop different autoregulation mechanisms in cerebral perfusion in order to maintain oxygen delivery to the brain in comparison to appropriate for gestational age (AGA) neonates. The aim of the current study was to estimate brain perfusion in SGA neonates during first postnatal week with the use of colour Doppler sonography. Patients/methods Transcranial Doppler sonography from the temporal acoustic window was performed bilaterally with CX50 PHILIPS device using S8–3 transducer in the first, third and seventh day of life of SGA neonates with mean gestational age 31.6 ± 2.2w and to comparable AGA ones. Recorded parameters were Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Mean Velocity (MV), Pulsatility Index (PI) and Resistance Index (RI) in middle cerebral artery MCA. Results 26 SGA and 26 matched for GA control AGA neonates were prospectively enrolled with statistically significant difference in birth weight (1.201, 9 ± 369.1 vs 1.805, 3 ± 431.7, p Conclusion Increased brain metabolism in the first postnatal days is responsible for the observed augmentation of cerebral perfusion in order to maintain the balance between oxygen delivery and consumption. It seems that SGA neonates manage to develop compensatory mechanisms probably with an increase of their brain perfusion.

Ghrelin and obestatin plasma levels and ghrelin/obestatin prepropeptide gene polymorphisms in small for gestational age infants

To investigate plasma ghrelin and obestatin levels, and ghrelin/obestatin prepropeptide gene polymorphisms, in sequentially enrolled small for gestational age (SGA) infants. Neonates were sequentially enrolled into this study and were then subdivided into different groups, according to different study aims and availability of study materials. Consequently, plasma ghrelin and obestatin levels were measured in term SGA, term appropriate for gestational age (AGA), term large for gestational age (LGA), preterm SGA and preterm AGA neonates. Levels of both peptides were also measured in AGA infants of different gestational ages, and in term AGA neonates at different days following birth. Three ghrelin/obestatin prepropeptide gene single nucleotide polymorphisms (SNPs), Arg51Gln, Leu72Met, and Gln90Leu, were measured in neonates. The study involved a total cohort of 581 neonates. Out of 150 neonates (30 term AGA, 30 term SGA, 30 term LGA, 30 preterm AGA, and 30 preterm SGA), plasma obestatin levels were significantly higher in term SGA versus term LGA neonates (0.21 ± 0.02 ng/ml versus 0.17 ± 0.01 ng/ml, respectively). Out of a wider cohort, there were no significant differences in genotypes and allele frequencies of Arg51Gln, Leu72Met, and Gln90Leu SNPs between term SGA and AGA neonates, or between preterm SGA and AGA neonates. Ghrelin/obestatin prepropeptide polymorphisms were not found to be associated with SGA status in neonates; however, ghrelin and obestatin levels may be involved in growth and development. Further studies are required to understand the relationship between ghrelin, obestatin and prenatal development.

Umbilical cord plasma and salivary insulin and leptin concentrations in AGA neonates: a preliminary report

Background and objective: Insulin and leptin hormones are important regulators of food intake and energy balance. There is limited information about insulin and leptin hormones in neonates. This preliminary study aimed to investigate the concentrations of insulin and leptin in umbilical cord plasma and neonate’s saliva and their relationships.Methods: Umbilical cord plasma and salivary samples were obtained from 13 healthy, appropriate for gestational age (AGA) neonates. Insulin and leptin concentrations in umbilical cord plasma and saliva were measured using the MILLIPLEX MAP® Human Metabolic Hormone Magnetic Bead Panel.Results: Insulin concentrations in umbilical cord plasma correlates positively and significantly with leptin concentrations in umbilical cord plasma (r = 0.55, p = 0.04).Conclusions: More research is needed to explore the relationships between insulin and leptin hormones in neonate’s saliva.

Neonatal cardiac dysfunction in intrauterine growth restriction

The early postnatal cardiovascular consequences of intrauterine growth restriction (IUGR) have not been completely elucidated. This study aimed to evaluate the effect of IUGR on neonatal myocardial function and cardiovascular adaptation to extrauterine life. Conventional and tissue Doppler echocardiographic parameters were compared on the second and fifth postnatal day between 30 IUGR and 30 appropriate-for-gestational age (AGA) neonates. IUGR neonates presented relative interventricular septum (IVS) hypertrophy (IVS to left ventricular (LV) posterior wall diastolic ratio: median IUGR-AGA difference of 0.05 (interquartile range: 0.04-0.06); P = 0.020), relative LV dilatation (wall thickness to end-diastolic LV dimension difference of 0.12 (0.06-0.16); P = 0.012), and increased left myocardial performance index (MPI difference of 0.19 (0.05-0.28); P = 0.012). Repeated measurements ANOVA revealed a different pattern of change in LV stroke volume (LVSV; P < 0.001), LV cardiac output (LVCO; P < 0.001), MPI (P < 0.001), and heart rate (HR; P = 0.025) between AGA and IUGR infants. From the second to the fifth postnatal day, AGA neonates presented a decrease in MPI and HR with an increase in LVSV and LVCO. IUGR neonates failed to achieve similar changes in MPI, HR, and LVSV, whereas their LVCO decreased. IUGR neonates present changes in cardiac morphology and subclinical myocardial dysfunction, which may result in an altered pattern of cardiovascular adaptation to extrauterine life.

Necrotizing Enterocolitis in Small-for-Gestational-Age Neonates: A Matched Case-Control Study

Background: Small for gestational age (SGA) neonates are at increased risk of mortality and morbidity, including necrotizing enterocolitis (NEC), but detailed information on the incidence and risk factors of NEC in SGA neonates is lacking. Objective: This study aims to estimate the incidence of NEC in a large cohort of SGA neonates, compared to appropriate for gestational age (AGA) neonates. Methods: We included all SGA neonates without congenital malformations admitted to our neonatal nursery between 2004 and 2013. Neonates in the SGA group were matched for gestational age with a control group of AGA neonates admitted during the same study period. We recorded the occurrence of NEC and studied the association with SGA and other potential risk factors. Results: A total of 475 SGA neonates were matched for gestational age at birth to 475 control AGA neonates. The incidence of NEC in the SGA group was 3.2% (15/475) versus 1.3% (6/475) in the AGA group (OR 2.55, 95% CI 0.98-6.63, p = 0.047). The incidence of NEC in the subgroups with mild, moderate and severe SGA was 2.3% (5/215), 4.7% (5/1.07) and 3.2% (5/153), respectively (p = 0.531). Conclusions: The risk of development of NEC is more than twofold increased in SGA neonates compared to AGA neonates. We found no association between the severity of SGA and NEC.

Impact of small‐for‐gestational age (SGA) status on gentamicin pharmacokinetics in neonates

We compared gentamicin pharmacokinetics among neonates born small-for-gestational age (SGA) and appropriate for gestational age (AGA). We further compared gentamicin pharmacokinetics in subgroups of AGA and SGA neonates born preterm and term and treated within and after the initial week of age. Steady state peak and trough serum gentamicin concentrations were used to calculate clearance (Cl), elimination constant (Kel), volume of distribution (Vd), and half-life (t1/2 ) in infants (n = 236) who received ≥48 hours therapy. Statistical analyses (SPSS 17.0) included chi-square and the non-parametric Mann-Whitney U-test. SGA infants treated early (≤7days) (n = 29) and at postmenstrual ages ≤32 weeks (n = 23) had significantly lower median Kel (0.069/h vs. 0.081/h and 0.067/h vs. 0.075/h) and clearance (0.58 mL/kg/min vs. 0.68 mL/kg/min and 0.46 mL/kg/min vs. 0.65 mL/kg/min), compared to those born AGA. There were no significant differences in pharmacokinetic profiles with later therapy or at more mature ages. The prolonged half-life of gentamicin may need to be considered in dosing regimens for preterm SGA infants in the initial week of life.

Association of placental perfusion, as assessed by magnetic resonance imaging and uterine artery Doppler ultrasound, and its relationship to pregnancy outcome

PurposeTo investigate (a) if placental perfusion in the second trimester of pregnancy, measured by two non-invasive magnetic resonance imaging (MRI) techniques, is related to impedance to flow in the uterine arteries, as assessed by Doppler ultrasound; and (b) if these measures are associated with future gestational outcome. MethodsIn 37 singleton pregnancies at 24–29 weeks' gestation, uterine artery pulsatility index (PI) was measured by Doppler ultrasound and placental perfusion was measured by Arterial Spin Labelling (flow-sensitive alternating inversion recovery (FAIR)) and intravoxel incoherent motion (IVIM) echo-planar imaging at 1.5 T in basal, central and placental regions of interest. The values were compared between those delivering small for gestational age (SGA) and appropriate for gestational age (AGA) neonates. ResultsIn 23 pregnancies that resulted in delivery of SGA neonates, compared to the 14 with AGA neonates, the median basal FAIR measure was significantly lower (923.0 vs. 2359.0 arbitrary units; p = 0.003) as were IVIM measures of perfusing fraction (f) in basal, central and whole-placental regions (37.8 vs. 40.7%; p = 0.046; 24.3 vs. 35.1%; p = 0.014 and 27.9% vs. 36.2%; p = 0.001, respectively). In the SGA group, the median uterine artery PI was increased (1.96 vs. 1.03; p = 0.001). There were significant associations between uterine artery PI and placental perfusion assessed by both FAIR and IVIM. ConclusionPregnancies that result in SGA neonates exhibited reduced placental perfusion as assessed by MRI during the second trimester. This measurement was found to be strongly associated with impedance to flow in the uterine arteries. We suggest that FAIR or IVIM MRI examinations may be used to directly and non-invasively determine placental perfusion, and that the measured values are strong indicators of future gestational outcome.

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

ObjectiveLarge- (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. MethodsCord 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. ResultsCord 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). ConclusionsThe 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.

The placental factor in early- and late-onset normotensive fetal growth restriction

ObjectiveOur objective was to investigate the placental component in early- and late-onset fetal growth restriction (FGR) compared to placentas from neonates appropriate for gestational age (AGA). Study designPlacentas from normotensive women who gave birth at 24–42 weeks to neonates with a birth-weight below the 10th percentile (FGR group), or to healthy AGA neonates (AGA group), were analyzed. Placental lesions were classified to lesions related to maternal underperfusion, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions. Findings were compared between patients who delivered ≤34 weeks (early-onset FGR) or >34 weeks (late-onset FGR) and controls with AGA neonates. ResultsThe early-onset FGR group (n = 24) had a higher rate of placental vascular lesions related to maternal underperfusion than the late-FGR group (n = 334) (41.7% vs. 8.7%, P < 0.001) and more villous lesions related to maternal underperfusion than the preterm AGA group (n = 68) (70.8% vs. 5.9%, P < 0.001). The late-onset FGR group had more placental villous lesions related to maternal underperfusion (57% vs. 19% P < 0.001) and more lesions consistent with fetal thrombo-occlusive disease (26.3% vs. 8.5%, P < 0.001) than the term AGA group (n = 153). ConclusionEarly- and late-onset FGR have different placental pathology compared with AGA controls, suggesting that a combination of fetal and maternal vascular compromise is more dominant in the late-onset FGR, rather than more severe maternal vascular compromise in early-onset FGR.

Assessment of iron status and red cell parameters in healthy full term small for gestational age neonates at birth

Background:Hematological values of the newborn babies vary according to the gestational age and intrauterine growth.Objective:The objective of this study is to compare the iron status and red cell parameters in healthy term small for gestational age (SGA) and appropriate for gestational age (AGA) neonates.Materials and Methods:A prospective hospital based study was conducted in a tertiary care teaching institution of central India. 50 AGA and 50 SGA neonates were included in the study and serum iron, serum ferritin and red cell parameters (hemoglobin (Hb), red blood cell (RBC) count and hematocrit (Hct), mean corpuscular volume (MCV), means corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW]) were estimated within 24 h of birth.Results:Serum ferritin levels were significantly low in SGA neonates as compared with AGA (mean 103 vs. 158 ng/ml; P=0.001) neonates. In SGA neonates, mean values of Hb (P=0.001), RBC count (P=0.018) and Hct (P=0.005) were significantly higher than in AGA neonates. Higher values of RDW and MCV were seen in SGA group in comparison with AGA neonates. Similarly, lower values of serum iron, MCH and MCHC were seen in the same group; although, these were non-significant.Conclusion:Despite higher Hb content, SGA neonates are deficient in iron store at birth as indicated by lower serum ferritin levels in them and early iron supplementation should be considered in them.

Cord blood nesfatin-1 in large for gestational age pregnancies

ObjectiveTo investigate possible alterations in cord blood levels of adipokine nesfatin-1 (secreted by adipose tissue and pancreatic β-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 methodsCord 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. ResultsCord 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. ConclusionsIn 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.

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.

1216 Intrauterine Growth Restriction and Developmental Programming of Renal Disease

Background and AimsIntrauterine growth restriction (IUGR) complicated by umbilical artery vasculopathy may have adverse effects on integrity and function of vascular endothelium and has been associated to atherosclerosis and to...

Size at birth and insulin-like growth factor-I and its binding protein-1 among infants of diabetic mothers

Objective: to estimate the association between intrauterine fetal growth, evaluated by anthropometric measurements, and biochemical growth factors; IGF-I and IGBP-1 among IDMs. Methods: Cross-sectional study carried out on 69 full term IDMs who was admitted to neonatal intensive care units, Ain Shams University Hospitals. Clinical examination including anthropometric measurements; birth weight, length, head circumference, mid-arm circumference, skinfold thickness at triceps and subscapular areas and placental weight. Laboratory investigations included maternal HbA1c and cord blood IGF-I and IGBP-1. They were classified into three groups: 20 small for gestational age (SGA), 25 appropriate for gestational age (AGA) and 24 large for gestational age (LGA). Results: Most of SGA neonates were born to mothers with type I diabetes, while most of AGA and LGA were born to mothers with gestational diabetes. According to maternal HbA1c, SGA and LGA neonates were born to metabolically uncontrolled mothers while AGA neonates were born to well-controlled diabetic mothers. Anthropometric measurements had significant positive correlations with IGF-I and negative correlations with IGFBP-1. Conclusions: Good control of diabetes during pregnancy is essential to improve fetal growth. There is an opposing effect of cord blood IGF-I and IGFBP-1 on anthropometric measurements.

Umbilical cord and fifth-day serum vaspin concentrations in small-, appropriate-, and large-for-gestational age neonates

Vaspin is a visceral adipose tissue-derived serine protease inhibitor that has an insulin-sensitizing effect. It is correlated with insulin resistance and glucose metabolism, and it improves glucose tolerance. The aim of this study was to determine and compare serum vaspin and insulin concentrations in small-for- gestational age (SGA), appropriate-for-gestational age (AGA), and large-for-gestational age (LGA) infants at birth and fifth postnatal day. Eighty-two neonates were divided into three groups: SGA (n=22), AGA (n=30), and LGA (n=30). Mothers' age, gestational week, mode of delivery, and maternal diseases, such as diabetes, pre-eclampsia, and eclampsia were recorded. Blood for vaspin, insulin, and glucose was collected from the cord at birth and from a peripheral vein on the fifth postnatal day. At birth, there were no statistically significant difference in serum insulin concentrations among the three groups, whereas cord serum vaspin concentrations were significantly higher in the SGA group (χ2=8.158, p<0.05). Serum glucose and vaspin levels on the fifth postnatal day had no significant difference among three groups (p<0.05). Circulating vaspin concentrations were not associated with the sex of the infant and delivery route. Cord vaspin levels are significantly higher in SGA neonates than in AGA or LGA neonates. The fetal programming hypothesis proposes that many adulthood diseases originate from the adaptation that the fetus makes when it is undernourished. High cord-vaspin levels in SGA infants may be one of the adaptations for increased risk for adult metabolic diseases.

Effect of small for gestational age on hemodynamic parameters in the neonatal period

Objective: The time course over which hypertension develops in children with a history of growth restriction has not been fully elucidated. The purpose of this study was to determine whether commonly obtained hemodynamic parameters were different between small for gestational age (SGA) and appropriate for gestational age (AGA) neonates. Methods: This was a retrospective case–control study matching 24 SGA neonates in a 1:2 fashion with 48 AGA neonates delivered during the same gestational week. Hemodynamic parameters were evaluated during the first week of life and the week prior to discharge. Results: There were no differences in blood pressure (BP) parameters during the first week of life. Compared to AGA controls, SGA neonates had a significantly lower heart rate (HR) at birth (148.2 ± 19.2 vs. 159.2 ± 17.1, p < 0.001), and a greater need for vasopressor support (OR 5.66; 95% CI 2.28, 14.04). The SGA neonates had a lower systolic BP during the week prior to discharge (68.3 ± 1.2 vs. 73.5 ± 1.2 mmHg, p < 0.001). Conclusions: SGA newborns had a lower HR at birth and greater need for vasopressor support during the first week of life despite similar BP parameters. SGA newborns had a lower systolic BP prior to discharge. Further studies are needed to understand the progression to adult hypertension.

Cord ghrelin levels are decreased in large-for-gestational-age neonates.

Ghrelin is a growth hormone secretagogue peptide and has been recognized as an orexigenic factor. To investigate relationship between cord ghrelin and anthropometric and metabolic indices, we measured cord ghrelin in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) neonates and examined whether cord ghrelin levels were correlated to concentrations of cord blood glucose, insulin, lipid and maternal ghrelin. Fifty-five singletons born at term and their mothers were investigated in this study. Maternal venous blood samples were collected before delivery. Plasma concentrations of ghrelin, insulin, glucose, total cholesterol, triacylglycerol (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol were measured in cord blood sampled at birth. The results show that the concentrations of cord ghrelin are significantly lower in LGA neonates. There is a positive correlation between cord ghrelin levels and maternal ghrelin levels. Negative correlations are found between cord ghrelin levels and gestational age, the concentrations of cord glucose, insulin, TG and LDL. Multivariate regression analyses show that birth weight (r(2) = 0.674, β = -0.548, P < 0.001) was the predictor correlating with ghrelin levels. In conclusion, LGA neonates have lower cord ghrelin concentrations than AGA neonates.

Intrauterine growth restriction may not suppress bone formation at term, as indicated by circulating concentrations of undercarboxylated osteocalcin and Dickkopf-1

The objective was to investigate circulating concentrations of bone formation markers (undercarboxylated osteocalcin [Glu-OC], an established marker of bone formation during fetal and early postnatal life], and Dickkopf-1 [DKK-1], a natural inhibitor of osteoblastogenesis during fetal development]) in intrauterine-growth–restricted (IUGR; associated with impaired fetal skeletal development) and appropriate-for-gestational-age (AGA) pregnancies. Circulating concentrations of Glu-OC and DKK-1 were determined by enzyme immunoassay in 40 mothers and their 20 asymmetric IUGR and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and 4 (N4). Parametric tests were applied in the statistical analysis. No significant differences in Glu-OC concentrations were observed between IUGR and AGA groups, whereas fetal DKK-1 concentrations were lower in the IUGR group (P = .028). In both groups, maternal Glu-OC and DKK-1 concentrations were lower than fetal, N1, and N4 concentrations (P ≤ .012 in all cases), whereas fetal Glu-OC concentrations were higher than N1 and N4 ones (P ≤ .037 in all cases). In addition, N1 Glu-OC concentrations were higher than N4 concentrations (P = .047). Finally, maternal Glu-OC and DKK-1 concentrations positively correlated with fetal, N1, and N4 ones (r ≥ 0.404, P ≤ .01 in all cases). Fetal/neonatal bone formation may not be impaired in full-term asymmetric IUGR infants, as indicated by the similar Glu-OC concentrations in both groups. Fetal DDK-1 concentrations are lower in the IUGR group, representing probably a compensatory mechanism, favoring the formation of mineralized bone. Fetal/neonatal bone turnover is markedly enhanced compared with maternal one and seems to be associated with the latter in both late pregnancy and early postpartum.

Longitudinal trends in fetoplacental biochemical markers, uterine artery pulsatility index and maternal blood pressure during the first trimester of pregnancy

To assess trends in levels of biochemical markers, uterine artery (UtA) pulsatility index (PI) and maternal blood pressure changes over time and study their relationships in uncomplicated first-trimester pregnancies. The study population comprised 86 women with singleton pregnancies. In each woman, a blood sample was collected at 6-7, 8-9, 10-11 and 12-13 weeks' gestation. At the same visit blood pressure was measured and ultrasound examination was performed to measure the crown-rump length and Doppler flow velocity waveform patterns of both UtAs. Serum concentrations of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), A disintegrin and metalloprotease domain-containing protein-12 (ADAM-12), placental protein-13 (PP-13) and placental growth factor (PlGF) levels were measured in thawed specimens using an automated time-resolved fluorescence assay. Summary curves were created to describe normal ranges and trends over time. The data were analyzed with a linear mixed model with the log-transformed marker values as dependent variables. This allowed for flexible modeling of patterns over time. Sixty-eight pregnancies had an uneventful outcome, with the birth of an appropriate-for-gestational-age (AGA) infant. In these pregnancies serum PAPP-A, ADAM-12, PP-13 and PlGF levels increased with gestational age. The UtA-PI decreased and the mean arterial blood pressure remained constant. There were no significant correlations between maternal age, birth-weight percentile, gender and blood pressure and any of the biochemical markers. The serum markers were highly correlated with each other except for β-hCG. A negative correlation was found between most biomarkers and UtA-PI, especially from 10 weeks onwards. Serum concentrations of ADAM-12 and PP-13 were lower in a small-for-gestational-age (SGA) subgroup born at term (n = 6), the former statistically significantly (P = 0.031), the latter non-significantly (P = 0.054), whereas UtA-PI was significantly higher (P = 0.02). Biomarker concentrations in 12 women delivering a large-for-gestational age infant did not differ from those delivering AGA neonates. There is a relationship between biochemical markers of early placentation and downstream resistance to flow in the UtAs in low-risk uncomplicated pregnancies, indicating differences in placentation. In a small series of SGA infants born at term we could demonstrate differences as compared to normal pregnancies, with potential value for screening.

Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance

ObjectiveTo investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants. Patients and methodsForty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay. ResultsHOMA-IR, apelin and visfatin levels (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels. ConclusionBased on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.