Intrauterine Growth Restriction Newborns Research Articles

Arginine bioavailability and endothelin-1 system in the regulation of vascular function of umbilical vein endothelial cells from intrauterine growth restricted newborns

Background and aimsIntrauterine growth restriction (IUGR) is a major risk factor for perinatal morbidity and mortality, leading to long-term adverse cardiovascular outcomes. The present study aimed to investigate the potential mechanisms in IUGR-associated vascular endothelial dysfunction. Methods and resultsHuman umbilical vein endothelial cells (HUVECs) were derived from IUGR or normal newborns. We found that the proliferation of IUGR-derived HUVECs was accelerated compared to those from normal subjects. Gene profiles related to vascular function including vasomotion, oxidative stress, and angiogenesis were dysregulated in IUGR-HUVECs. Compared with HUVECs from normal newborns, nitric oxide (NO) production was reduced, with imbalance between endothelial nitric oxide synthase (eNOS) and arginase-2 (Arg-2) in IUGR. Meanwhile, intracellular asymmetric dimethylarginine (ADMA) level was elevated with diminished dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression in IUGR-HUVECs. Furthermore, endothelin-1 (ET-1) and hypoxia-inducible factor 1α (HIF-1α) expression were increased, and endothelin receptor type-B (ETBR) was reduced in the IUGR group. IUGR-HUVECs exposed to hypoxia increased the ratio of ADMA to l-arginine, HIF-1α and protein arginine methyltransferase 1 (PRMT1) expression compared to controls. ConclusionsThe present study demonstrated that the reduction of NO bioavailability and release results from elevated Arg-2, accumulation of intracellular ADMA, and imbalance of ET-1 and ETBR, further leading to IUGR-associated vascular endothelial dysfunction. Our study provides novel evidence on the mechanism underlying fetal programming associated with IUGR, which will serve as potential therapeutic targets in the prevention of adverse cardiovascular consequences in adulthood.

Disparities of Clinical Features and Associated Maternal Factors among Symmetrical and a Symmetrical Intra-Uterine Growth Restriction (IUGR) in NICU at Al-Yarmouk Teaching Hospital in Baghdad, Iraq

Background: Worldwide Intra-Uterine Growth Restriction carries out high rate of fetal and neonatal morbidity and mortality. Perinatal mortality rates are 4-8 times higher for growth-retarded infants. IUGR are subdivided into symmetrical and asymmetrical subtypes. Aim of Study: To focus on the actual incidence of each subtype of IUGR and disparities. Methods: Across-sectional descriptive study applied on 52 singleton newborns admitted to the NICU at Al-Yarmouk Teaching Hospital, Baghdad, Iraq, from January to December2015.We assessed them for some demographic characteristics, anthropometric measures, investigation and a thorough physical examination with an estimation of the Ponderal Index (PI) values; these data were analyzed using SPSS version 18.0 software.Results: We found equal gender distribution for each sex. The 63.46% of IUGR babies was of asymmetrical type while 36.53%wassymmetrical.Incidencerate was higher among multiparous mothers than primiparous as 51.9%. The asymmetrical subtype mostly delivered by NVD 63.6% while the symmetrical subtype mostly delivered by CS delivery 68.4 %. RDS was the commonest early complication, the higher percentage was among symmetrical than asymmetrical subtypes 57.9%, 27.3%, respectively. Among all deaths 33.35% had asymmetrical subtype. The mean birth weight for a symmetrical subtype was 1.41 kg, while for the symmetrical subtype it was 1.76 kg.Conclusion: The asymmetrical IUGR newborns were more than symmetrical type. More than two thirds of symmetrical IUGR were delivered with Cesarean section, while more than two thirds of asymmetrical IUGR were delivered normally and more than half of symmetrical IUGR were with RDS. Sex had no effect on IUGR distribution.

The Association of Oxidative Stress and Hypoglycemia in Reduced Uterine Perfusion Rat Offspring

Background: Intrauterine growth restriction (IUGR) is a significant cause of morbidity and mortality in the neonatal period. Hypoglycemia is often reported in IUGR newborns which may have permanent sequelae if severe. IUGR is commonly associated with placental insufficiency resulting in reduced transport of nutrients and oxygen to the fetus, however, the exact mechanisms involved are unknown. In utero, the placenta shows increased oxidative stress in the setting of placental insufficiency and it is unclear how oxidative stress may influence the development of a hypoglycemic state in …

Markers of obesity and growth in preeclamptic and normotensive pregnant women

The objective of the study was to analyse leptin, IGF-1, Apo A, lipoproteins, haem oxygenase-1 (HO-1) in maternal sera and venous umbilical cord sera of newborn babies of 25 preeclamptics (group II), and 25 normotensive pregnant women (group I) as markers of obesity and growth in preeclamptic and normotensive pregnant women. Apo A I and II levels were estimated by competitive immunoassay using direct chemiluminiscence technology. Haem oxygenase-1 (HO-1), leptin and IGF-1 were analysed by ELISA. Maternal and cord blood levels of homocysteine, folic acid, lipid profile (namely, total cholesterol, triglycerides, LDL-C, VLDL-C and HDL-C), Haem oxygenase 1 were higher in preeclamptic women as compared to normotensive pregnant women. Serum and cord blood Apo A-I and Apo B, leptin levels, IGF-I were lower in preeclamptic women as compared to normotensive pregnant. The findings of high serum HO-1 levels in maternal and cord blood in preeclampsia supports the role of oxidative stress and excessive inflammatory response in the pathogenesis of preeclampsia. It seems likely that IGF-1 and leptin play a central role in controlling foetal growth. There is increasing evidence that the foundations of life-long health are, in part, laid in the uterus. Findings of present study suggest that alterations in biochemical markers of growth and obesity occur in mothers and foetuses and modifications of uterine environment can be of help to prevent future cardiovascular risk.Impact statementPreeclampsia has been reported to be associated with an increased risk of later life cardiovascular disease. However, information regarding how obesity increases the risk of preeclampsia is limited. Atherogenic milieu occurring during pregnancy persists into adulthood and foetal growth retardation is strongly associated with adult atherosclerosis.There is conflicting evidence regarding alterations of IGFs in preeclamptic pregnancies and deficit in circulating and cord blood IGF-1 levels in intrauterine growth restricted newborns and a correlation between IGF-1 levels and birth weight have been reported. Leptin is a predictor of cardiovascular risk independent of insulin resistance. Emerging evidence supports an important role for the haem oxygenase system (HO-1) in the maintenance of a healthy pregnancy, especially during pathological challenge.Conflicting data are available regarding HO-1, leptin and IGF –1 in preeclamptic mothers. The extent to which they mediate foetal growth and developmental abnormalities remains to be clarified.Serum IGF-1 levels were significantly decreased in preeclamptics and maternal IGF-1 showed a strong inverse correlation with leptin levels. High serum HO-1 levels in maternal and cord blood in preeclampsia were observed in the present study.Findings of the present study suggest that alterations in biochemical markers of growth and obesity occur in mothers and foetuses and modifications of the uterine environment can be of help to prevent future cardiovascular risk.

Proteoform profiling of peripheral blood serum proteins from pregnant women provides a molecular IUGR signature

Intrauterine growth restriction (IUGR) is an important cause of perinatal morbidity and mortality and contributes substantially to medically indicated preterm birth; preventing fetal death. Molecular profiling of the mothers' peripheral blood was desired to monitor the health conditions of the fetuses. To develop such a minimally invasive assay, we applied a protein affinity fractionation method to peripheral blood serum samples from pregnant women belonging to either the IUGR or to the control group. Proof-of-principle was shown by relative quantitation analysis of mixtures of intact proteoforms using MALDI-ToF mass spectrometry. The two best differentiating proteins and proteoforms, respectively, were apolipoprotein C-II and apolipoprotein C-III0. Together with three robustly expressed protein proteoforms proapolipoprotein C-II, apolipoprotein C-III1, and apolipoprotein C-III2, which served as landmarks for relative quantitation analysis, they constituted the maternal IUGR proteome signature. Separation confidence of our IUGR proteoform signature reached a sensitivity of 0.73 and a specificity of 0.87 with an area under curve of 0.86 in receiver operator characteristics. SignificanceIdentification of IUGR newborns in the case room is required as children are severely diseased and need specialized care during infancy. Yet, at time of birth there is no readily applicable clinical test available. Hence, a molecular profiling assay is highly desired.It needs to be mentioned that current clinical definitions and recommendations for IUGR are unfortunately misleading and are not universally applicable. The most commonly adopted definition is an abdominal circumference (AC) or estimated fetal weight measurement <10th percentile. Although both, the American College of Obstetricians and Gynecologists (ACOG) and the Royal College of Obstetricians and Gynecologists (RCOG) agree that at this cut-off the risk of perinatal morbidity and mortality increases, this definition does not take into account the individualized growth potential of each fetus. In particular its sole use fails to identify larger fetuses that have not achieved their growth potential and may be at risk of adverse outcomes. Also, this definition, when solely applied, will result in the misdiagnosis of IUGR for some constitutionally small fetuses. It needs to be pointed out that the above mentioned criteria can only be determined during pregnancy in case mothers report from early on during pregnancy.We have developed a test that relies on mass spectrometric analysis of the mother's serum protein composition (IUGR signature) which can be determined just ahead of delivery and at date of delivery, respectively using a minimal invasive blood sampling approach. With this manuscript we describe the use of a mass spectrometric profiling method of 30 peripheral blood samples from pregnant women prior to giving birth of either unsuspicious newborns or IUGR-affected infants.We report for the first time that maternal blood sample analysis via affinity mass spectrometry differentiates IUGR infants from controls with high confidence.

Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler.

IntroductionInfant anthropometry and body composition have been previously assessed to gauge the impact of intrauterine growth restriction (IUGR) at birth, but the interplay between prenatal Doppler measurements and postnatal development has not been studied in this setting. The present investigation was performed to assess the significance of prenatal Doppler findings relative to postnatal anthropometrics and body composition in IUGR newborns over the first 12 months of life.Patients and MethodsConsecutive cases of singleton pregnancies with suspected IUGR were prospectively enrolled over 12 months. Fetal biometry and prenatal Doppler ultrasound examinations were performed. Body composition was assessed by absorptiometry at ages 10 days, and at 4 and12 months.ResultsA total of 48 pregnancies qualifying as IUGR were studied. Doppler parameters were normal in 26 pregnancies. The remaining 22 deviated from normal, marked by an Umbilical Artery Pulsatility Index (UA-PI) >95th centil or Cerebro-placental ratio (CPR) <5th centile. No significant differences emerged when comparing anthropometry and body composition at each time point, in relation to Doppler findings. Specifically, those IUGR newborns with and without abnormal Doppler findings had similar weight, length, body mass index, lean and fat mass, and bone mineral content throughout the first 12 months of life. In a separate analysis, when comparing IUGR newborns by Doppler (abnormal UA-PI vs. abnormal CPR), anthropometry and body composition did not differ significantly.ConclusionsInfants with IUGR maintain a pattern of body composition during the first year of life that is independent of prenatal Doppler findings. Future studies with larger sample sizes and correlating with hormonal status are warranted to further extend the phenotypic characterization of the various conditions now classified under the common label of IUGR.

Índices y velocidades de la arteria uterina como indicadores de hipoperfusión uterina en gestantes con restricción del crecimiento intrauterino

Objetivo: Evaluar los índices y velocidades de la arteria uterina como indicadores de hipoperfusión uterina en gestantes con restricción del crecimiento intrauterino. Diseño: Estudio analítico, de casos y controles. Institución: Hospital III Honorio Delgado de Arequipa, Perú. Participantes: Treinta gestantes con restricción del crecimiento intrauterino (RCIU) con peso del recién nacido menor al percentil 10; el grupo control estuvo conformado por 80 gestantes normales en el tercer trimestre. Metodología: Entre julio del 2013 y abril del 2014 se realizó ecografía Doppler de las arterias uterinas en las gestantes que participaron del estudio, se calculó los índices y velocidades de las arterias uterinas, se comparó las medias y se hizo pruebas de validez diagnóstica de RCIU. Principales medidas de resultados: Índices y velocidades de las arterias uterinas. Resultados: La media de la edad gestacional para los grupos de RCIU y control fueron 35,7 y 36,2 semanas, respectivamente. La media del peso de los RN con RCIU fue 1 932,60 g. La velocidad media (MnV) presentó sensibilidad 73%, especificidad 95%, valor predictivo positivo (VPP) 85%, valor predictivo negativo (VPN) 90%, odds ratio (OR) 52 y razón de verosimilitud de 14,6. Los índices de pulsatilidad (IP) y de resistencia (IR) mostraron sensibilidad de 27%, especificidad 95%, VPP 67%, VPN 78%, OR 6,9 y razón de verosimilitud 5,3. Conclusiones: Las velocidades y especialmente la velocidad media de la arteria uterina tuvieron mejor sensibilidad, VPP, VNP, OR y razón de verosimilitud que los índices, como indicadores de hipoperfusión uterina en gestantes con restricción del crecimiento intrauterino.

Histomorphometry of umbilical cord and perinatal outcome in intrauterine growth restriction

Objective: To evaluate the histomorphometry of umbilical cord (UC) in intrauterine growth restricted (IUGR) newborns compared to appropriate for gestational age (AGA) newborns, and secondly to assess its impact on the intrapartum and perinatal outcome. Materials and Methods: A prospective observational study was conducted at Obstetrics and Gynecology unit of KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi. Study involved total 130 UCs of AGA and IUGR newborns. Tissues were fixed in formalin and paraffin embedded sections were examined. For each UC; UC cross sectional area (CSA), UC diameter and UC circumference parameters were measured under microscope with the help of digital image analyzer. Perinatal outcome like gestational age (GA) at delivery, birth weight, mode of delivery, sex of newborn, neonatal outcome and intrapartum complications were recorded. Independent t test was used to compare means and chi-square test for categorical variables. Results: UC of IUGR newborns had significantly reduced UC area, diameter and circumference as compared to AGA newborns. IUGR newborns were associated with significant difference in GA at delivery, birth weight, neonatal intensive care unit admissions (NICU) and fetal distress. No significant difference was found in mode of delivery, sex of newborn and meconium stained liquor among AGA and IUGR groups. Conclusion: Assessment of CSAs of UC and its components can be used as early screening tool for fetal growth and it may provide useful information about pregnancy at risk and help in averting poor perinatal outcome.

Programmed regulation of rat offspring adipogenic transcription factor (PPARγ) by maternal nutrition.

We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPARγ with variable changes in co-repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPARγ with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPARγ expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPARγ co-regulators are necessary to establish their role in PPARγ-mediated programmed obesity.

Neonatal short-term outcomes in infants with intrauterine growth restriction.

Objectives:To assess the neonatal outcomes in newborns with intrauterine growth restriction (IUGR) in a Romanian population in a 3 level maternity unit.Methods:A matched case-control design, with one control for each patient was used. The case group comprised neonates with birth weight and birth length below the 10th percentile for the gestational age. Individual matching by gender and age of gestation was used to identify the control group. Both cases and controls were selected from the infants admitted to and discharged from the Neonatal Ward, at the First Gynecology Clinic, of the County Emergency Hospital Cluj-Napoca, Cluj-Napoca, Romania, between January 2012 and June 2014.Results:One hundred and forty-two subjects were included in each group. The cesarean delivery was significantly more frequent in the IUGR group (66.9%) compared with controls (46.5%; p=0.0006). The Apgar score at one minute was ≥7 for most infants in both groups (77.9% IUGR group versus 77.5% control group), with no significant differences between the groups. A significantly higher percentage of infants in the IUGR group had hypoglycemia or intraventricular hemorrhage compared with the controls (p<0.05). Hypoglycemia proved a significant factor for IUGR (odds ratio = 4.763, 95% confidence interval: 1.711-13.255).Conclusion:Hypoglycemia and intraventricular hemorrhage characterized the IUGR newborns.

Neural injury markers to predict neonatal complications in intrauterine growth restriction

We assessed the neural injury markers (NIMs) in maternal and umbilical blood in preterm deliveries with and without intrauterine growth restriction (IUGR), and relationship between NIMs and neonatal complications.Deliveries between 24 and 34 weeks’ gestation with (study group) and without (control group) IUGR were included to the study. Three NIMs (s100B, neurone-specific enolase [NSE] and alpha-foetoprotein [AFP]) were investigated in umbilical arterial, umbilical venous and maternal venous serum.Thirty-two IUGR and twenty-nine non-IUGR pregnancies with preterm delivery were included. Maternal and umbilical arterial s100B levels were significantly higher in the study group, whereas there was no relationship among IUGR, AFP and NSE levels. In the study group, umbilical venous s100B and NSE levels were associated with perinatal mortality (p = 0.012, 0.005, respectively), necrotising enterocolitis (NEC) (p = 0.001, 0.04, respectively) and need for intubation (p = 0.001, 0.007, respectively). Negative predictive values for perinatal mortality and NEC were 100% and for need for intubation it was 92.8% when both s100B and NSE were below the cutoff line determined by the receiver-operating characteristic curves.Perinatal mortality, NEC and need for intubation can be predicted by assessment of umbilical venous s100B and NSE measurement during birth in IUGR newborns.

Urinary metabolomics (GC-MS) reveals that low and high birth weight infants share elevated inositol concentrations at birth

Objective: Metabolomics is a new “omics” platform aimed at high-throughput identification, quantification and characterization of small-molecule metabolites. The metabolomics approach has been successfully applied to the classification different physiological states and identification of perturbed biochemical pathways. The purpose of the current investigation is the application of metabolomics to explore biological mechanisms which may lead to the onset of metabolic syndrome in adulthood.Methods: We evaluated differences in metabolites in the urine collected within 12 h from 23 infants with IUGR (IntraUterine Growth Restriction), or LGA (Large for Gestational Age), compared to control infants (10 patients defined AGA: Appropriate for Gestational Age). Urinary metabolites were quantified by GC-MS and used to highlight similarities between the two metabolic diseases and identify metabolic markers for their predisposition. Quantified metabolites were analyzed using a multivariate statistics coupled with receiver operator characteristic curve (ROC) analysis of identified biomarkers.Results: Urinary myo-inositol was the most important discriminant between LGA + IUGR and control infants, and displayed an area under the ROC curve = 1.Conclusion: We postulate that the increase in plasma and consequently urinary inositol may constitute a marker of altered glucose metabolism during fetal development in both IUGR and LGA newborns.

Corpus callosum differences assessed by fetal MRI in late-onset intrauterine growth restriction and its association with neurobehavior

The aim of this study is to evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriate for gestational age and its association with neurobehavioral outcome. One hundred and seventeen late-onset IUGR and 73 control fetuses were imaged using a 3T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale test was performed on IUGR newborns at 42 ± 1 weeks. IUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and/or abnormal brain and/or abnormal uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases. CC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk.

Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum of IUGR newborns

Aim: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA).Materials: Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010–2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329 ± 287 g); control group, enclosing 50 infants AGA (average weight: 3544 ± 2161 g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4–6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov–Smirnov test. Significance level: p < 0.05.Results: Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group.Conclusions: An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.

Site-specific methylation of placental HSD11B2 gene promoter is related to intrauterine growth restriction

Intrauterine growth restriction (IUGR) is associated with detrimental effects on neurodevelopmental progress in childhood and higher risk of degenerative diseases in adulthood. Placental 11β-hydroxysteroid dehydrogenase (HSD11B2) is a key gene involved in glucocorticoid metabolism, which in turn seems to be related to fetal growth impairment. As reduction of placental HSD11B2 gene expression has been associated with reduced human fetal growth, and methylation of HSD11B2 gene promoter has been shown to have an important role in HSD11B2 gene repression, we seek to investigate the relationship between IUGR and HSD11B2 gene promoter methylation in human placentas. We found that methylation levels of all studied CpG sites were significantly higher in IUGR newborns than those in controls. Further, methylation levels of the first and the third CpG sites were inversely associated with measures of fetal growth (birth weight and ponderal index). In addition, consistent with the above negative correlation, methylation levels of the first and the third CpG sites were inversely associated with HSD11B2 gene expression. These results together show a link between the site-specific methylation of placental HSD11B2 promoter and the development of IUGR.

Developmental Programming of Offspring Obesity, Adipogenesis, and Appetite

A newly recognized primary cause of the obesity epidemic is the developmental programming effects of infants born to mothers with obesity or gestational diabetes, intrauterine growth-restricted newborns, and offspring exposed to environmental toxins including bisphenol A. The mechanisms which result in offspring obesity include the programming of the hypothalamic appetite pathway and adipogenic signals regulating lipogenesis. Processes include nutrient sensors, epigenetic modifications, and alterations in stem cell precursors of both appetite/satiety neurons and adipocytes which are modulated to potentiate offspring obesity. Future strategies for the prevention and therapy of obesity must address programming effects of the early life environment.

Metabolic and hormonal profiles in cord blood of idiopathic intrauterine growth-restricted newborns and associated maternal metabolic disorders

Metabolic and hormonal profiles in cord blood of idiopathic intrauterine growth-restricted newborns and associated maternal metabolic disorders

Mechanism of programmed obesity: altered central insulin sensitivity in growth-restricted juvenile female rats.

Intrauterine growth-restricted (IUGR) offspring are at increased risk of adult obesity, as a result of changes in energy balance mechanisms. We hypothesized that impairment of hypothalamic insulin signaling contributes to hyperphagia in IUGR offspring. Study pregnant dams were 50% food restricted from days 10 to 21 to create IUGR newborns. At 5 weeks of age, food intake was measured following intracerebroventricular (icv) injection of vehicle or insulin (10 mU) in control and IUGR pups. At 6 weeks of age, with pups in fed or fasted (48 h) states, pups received icv vehicle or insulin after which they were decapitated, and hypothalamic arcuate (ARC) nucleus dissected for RNA and protein expression. IUGR rats consumed more food than controls under basal conditions, consistent with upregulated ARC phospho AMP-activated protein kinase (pAMPK) and neuropeptide Y (NPY). Insulin acutely reduced food intake in both control and IUGR rats. Consistent with anorexigenic stimulation, central insulin decreased AMP-activated protein kinase and NPY mRNA expression and increased proopiomelanocortin mRNA expression and pAkt, with significantly reduced responses in IUGR as compared with controls. Despite feeding, IUGR offspring exhibit a persistent state of orexigenic stimulation in the ARC nucleus and relative resistance to the anorexigenic effects of icv insulin. These results suggest that impaired insulin signaling contributes to hyperphagia and obesity in IUGR offspring.

Copeptin: a marker for stress reaction in fetuses with intrauterine growth restriction

To compare venous cord plasma concentrations of 4 vasoactive peptide precursors: carboxy-terminal proarginine vasopressin, CT-prondothelin (ET)-1, midregional proadrenomedullin, and MR-proatrial natriuretic peptide, between fetuses with intrauterine growth restriction and appropriate for gestational age controls. Matched-pair analysis of 12 fetuses with significant intrauterine growth restriction and 42 healthy appropriate for gestational age control fetuses. All infants were singletons, delivered by elective section after 34 weeks and without chromosomal abnormalities. Umbilical cord plasma copeptin levels (median [range]) were 4-fold higher in intrauterine growth restriction infants than in matched appropriate for gestational age controls: 23.2 (6.7-449) vs 5.1 (2.5-53) pmol/L (P < .001). Multivariate regression analysis revealed an association between copeptin and umbilical artery resistance index z-score (P = .034). The 3 other precursor peptides showed no changes. High copeptin concentrations in the cord blood of intrauterine growth restriction newborns reflect a fetal stress response and support the fetal programming hypothesis.

Is it necessary to induce labor in cases of intrauterine growth restriction at term?

Infants with intrauterine growth restriction (IUGR) have increased morbidity and mortality. The decision whether to induce labor at term or to expectantly manage these pregnancies is controversial. The aim of this study was to assess the outcomes of these two management strategies in term pregnancies. This retrospective cohort study compared neonatal and maternal morbidity and mortality of IUGR fetuses (estimated fetal weight below the 10th percentile) between induced and spontaneous labors. Records of 669 IUGR newborns were reviewed; 499 were delivered through spontaneous labor and 170 were delivered through induced labor. Epidemiology and early perinatal outcomes between the two groups were similar. The cesarean section rate was significantly higher (P<0.005) in the induced group. Expectant management for term IUGR pregnancies seems to be safe, with lower rates of cesarean deliveries. A large, prospective, randomized controlled trial with long-term neonatal follow-up is indicated.