Intrauterine Growth Restriction Newborns Research Articles

Fetal sex and the relative reactivity of human umbilical vein and arteries are key determinants in potential beneficial effects of phosphodiesterase inhibitors.

Intrauterine growth restriction (IUGR) is a common complication of pregnancy. We previously demonstrated that IUGR is associated with an impaired nitric oxide (NO)-induced relaxation in the human umbilical vein (HUV) of growth-restricted females compared to appropriate for gestational age (AGA) newborns. We found that phosphodiesterase (PDE) inhibition improved NO-induced relaxation in HUV, suggesting that PDEs could represent promising targets for therapeutic intervention. This study aimed to investigate the effects of PDE inhibition on human umbilical arteries (HUAs) compared to HUV. Umbilical vessels were collected in IUGR and AGA term newborns. NO-induced relaxation was studied using isolated vessel tension experiments in the presence or absence of the nonspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX). PDE1B, PDE1C, PDE3A, PDE4B, and PDE5A were investigated by Western blot. NO-induced vasodilation was similar between IUGR and AGA HUAs. In HUAs precontracted with serotonin, IBMX enhanced NO-induced relaxation only in IUGR females, whereas in HUV IBMX increased NO-induced relaxation in all groups except IUGR males. In umbilical vessels preconstricted with the thromboxane A2 analog U46619, IBMX improved NO-induced relaxation in all groups to a greater extent in HUV than HUAs. However, the PDE protein content was higher in HUAs than HUV in all study groups. Therefore, the effects of PDE inhibition depend on the presence of IUGR, fetal sex, vessel type, and vasoconstrictors implicated. Despite a higher PDE protein content, HUAs are less sensitive to IBMX than HUV, which could lead to adverse effects of PDE inhibition in vivo by impairment of the fetoplacental hemodynamics.NEW & NOTEWORTHY The effects of phosphodiesterase inhibition on the umbilical circulation depend on the presence of intrauterine growth restriction, the fetal sex, vessel type, and vasoconstrictors implicated. The human umbilical vascular tone regulation is complex and depends on the amount and activity of specific proteins but also probably on the subcellular organization mediating protein interactions. Therefore, therapeutic interventions using phosphodiesterase inhibitors to improve the placental-fetal circulation should consider fetal sex and both umbilical vein and artery reactivity.

Risk factors for neonatal cholestasis in small gestational age infants: case report and literature review

Cholestatic jaundice, defined as conjugated bilirubin levels higher than 1 mg/dl, is a bile formation and excretion disturbance. Its incidence is estimated at 1 case in 2500 live births, being 100-200 times higher in preterm infants less than 28 weeks gestational age. It occurs in biliary atresia, infectious diseases, endocrine and inherited metabolic diseases, Alagille Syndrome, preterm and intrauterine growth-restricted newborns, lack of enteral feeding, and is more frequent in male gender. It is a frequent complication of parenteral nutrition. In preterm and small for gestational age (SGA) infants, the etiology of cholestasis is multifactorial. Early diagnosis enables early therapeutic intervention. We report the case of an SGA male preterm infant. He was born by C-section for fetal distress at 30 weeks gestational age with an 800 g birth weight. He developed mild respiratory distress, hypoglycemia, meconium ileus, and early cholestasis. Complex hematological, serological, and immunological tests were carried out; ultrasound evaluations were performed. The final diagnosis was cholestasis of multifactorial etiology in a preterm infant with severe intrauterine growth restriction (IUGR). Treatment with ursodeoxycholic acid was started. Three months later, the transaminases, bilirubin, gammaglutamyl transferase (GGT), and alkaline phosphatase (ALP) triglycerides returned to normal. Conclusion. Cholestasis in SGA infants is a severe condition potentially associated with life-threatening complications, requiring complex diagnostic evaluation.

Bone Status and Early Nutrition in Preterm Newborns with and without Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) together with preterm birth could be harmful to bone health. The aim of the study was to examine bone status in IUGR versus non-IUGR preterms and to analyze the nutritional management best correlated with its improvement. Newborns < 34 weeks of gestational age (wGA), 75 IUGR and 75 non-IUGR, admitted to the Neonatal Intensive Care Unit of the University Hospital of Padova were enrolled and monitored from birth until 36 wGA through anthropometry (weight, length, head circumference, lower limb length (LLL)), biochemistry, bone quantitative ultrasound assessment of bone status (metacarpus bone transmission time, mc-BTT, us) and nutritional intakes monitoring during parenteral nutrition. IUGR compared to non-IUGR showed lower mean mc-BTT (0.45 vs. 0.51, p = 0.0005) and plasmatic phosphate (1.45 vs. 1.79, p < 0.001) at birth. Mc-BTT at 36 wGA, though equal between groups, correlated in IUGR newborns with basal phosphate, mean total energy of the first week and month (positively) and days to reach full enteral feeding (negatively). Lower i.v. vitamin D intake, LLL and prolonged total parenteral nutrition predicted worse mc-BTT at 36 wGA in the enrolled infants. These results suggest that preterms and in particular IUGR newborns need special nutritional care to promote bone development.

Normative echocardiography data of myocardial adaptation to extrauterine life: a review of prospective studies.

Recent research has increased focus and interest in characterizing the physiology of the transition circulation using echocardiography. Critique of published normative neonatal echocardiography data among healthy term neonates has not been performed. We have performed a comprehensive literature review using the key terms: cardiac adaptation, hemodynamics, neonatal transition, term newborns. Studies were included if they had reported echocardiography indices of cardiovascular function in the presence of maternal diabetes, intrauterine growth restricted newborns and prematurity and had a comparison group of healthy term newborns within first seven postnatal days. Sixteen published studies evaluating transitional circulation in healthy newborns were included. There was marked heterogeneity in the methodologies used; specifically, inconsistency in time of evaluation and imaging techniques used makes it challenging to determine specific trends of expected physiologic changes. Some studies revealed nomograms for echocardiography indices, though limitations persist in terms of sample size, number of reported parameters and consistency of measurement technique. A comprehensive standardized echocardiography framework which includes consistent techniques for assessment dimensions, function, blood flow, pulmonary/systemic vascular resistance, and shunts pattern is warranted to ensure consistency in the use of echocardiography to guide care of healthy and sick newborns.

Evaluation of Oxidative Stress Markers in Relation APGAR Scores to in Egyptian Newborns with Intrauterine Growth Retardation

The study aimed to estimate the status of oxidative stress markers in neonates of both sexes born 37- 41with intrauterine growth restriction (IUGR) comparing them to healthy convenient for gestational. The study included 44 Egyptian neonates with IUGR of both sexes and 45 neonates of both sexes with appropriate for gestational age. In both groups the neonates were delivered vaginally without any assisted vaginal delivery to mothers without known medical conditions affecting placental sufficiency. Malondialdehyde (MDA, total antioxidant capacity (TAC) and paraoxonase-1(PON1) were measured. Obstetric data including mode of delivery, instrumental delivery and gestational age at delivery by ultrasound Neonatal assessment including gestational age by new Ballard, sex of neonate, weight, head circumference, APGAR score at 1 and 5 minutes, length, full general &amp; systemic examinations of newborn. The activity of MDA was increased, whilelevels of TAC and PON1 were significantly lower in IUGR than controls. APGAR score at both 1 min and 5 min and Ballard were significantly decreased in the IUGR group. Mean birth weight, length, maternal gestational age and head circumference of IUGR cases were decreased than control. APGAR scores were negatively correlated with MDA. In conclusion oxidative stress associated with IUGR newborns and antioxidants during pregnancy may be advised. Oxidative stress markers might have early prediction value for diagnosis of these conditions and probable pharmacological intervention with antioxidants may improve the pregnancy conditions.

Treatment of immune dysfunction in intrauterine growth restriction piglets via supplementation with dimethylglycine sodium salt during the suckling period.

This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction (IUGR) newborn piglets and relieve this dysfunction via dimethylglycine sodium salt (DMG-Na) supplementation during the suckling period. Thirty sows (Duroc × [Landrace × Yorkshire]) were selected, and 1 male newborn piglet with normal birth weight (NBW) and 1 male newborn piglet with IUGR were obtained from each sow. Among them, 10 NBW and 10 IUGR newborns were euthanized without suckling. The other 20 NBW newborns were allocated to the group named NCON, which means NBW newborns fed a basic milk diet (BMD) (n = 10), and the group named ND, which means NBW newborns fed BMD supplemented with 0.1% DMG-Na (n = 10); the other 20 IUGR newborns were assigned to the group named ICON, which means IUGR newborns fed BMD (n = 10), and the group named ID, which means IUGR newborns fed BMD supplemented with 0.1% DMG-Na (n = 10). The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples. The growth performance, small intestinal histological morphology and sub-organelle ultrastructure, serum immunoglobulin, small intestinal digestive enzyme activity, inflammatory cytokine level, and jejunum mRNA and protein expression of the toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain protein (NOD)/nuclear factor-κB (NF-κB) network deteriorated in the ICON group compared to that in the NCON group. The small intestinal histological morphology and sub-organelle ultrastructure, serum immunoglobulin, small intestinal digestive enzyme activity, and inflammatory cytokine level improved (P < 0.05) in the ID group compared to those in the ICON group. The jejunum mRNA and protein expression of the TLR4/NOD/NF-κB network improved (P < 0.05) in the ID group compared to that in the ICON group. In conclusion, the activity of the TLR4/NOD/NF-κB pathway was inhibited in the IUGR newborns, which in turn led to their jejunum immune dysfunction and reduced their performance. By ingesting DMG-Na, the IUGR newborns activated the TLR4/NOD/NF-κB pathway, thereby improving their unfavorable body state during the suckling period.

Supplementation of Dimethylglycine Sodium Salt in Sow Milk Reverses Skeletal Muscle Redox Status Imbalance and Mitochondrial Dysfunction of Intrauterine Growth Restriction Newborns.

The current study sought to understand the mechanism underlying skeletal muscle dysfunction brought on by intrauterine growth restriction (IUGR) and to explore the treatment benefits of applying dimethylglycine sodium salt (DMG-Na) in sow milk to newborns during the suckling period. Each of the 10 sows delivered one newborn with a normal birth weight (NBW) and one with an IUGR. Additionally, two NBW and two IUGR newborns were collected per litter of another 10 sows. The 20 NBW newborns were divided between the N (sow milk) and ND (sow milk + 0.1% DMG-Na) groups, while 20 IUGR newborns were divided between the I (sow milk) and ID (sow milk + 0.1% DMG-Na) groups. The skeletal muscle histomorphology, redox status, and levels of gene and protein expression were worse (p < 0.05) in the I group than in the N group. In addition, supplementation with DMG-Na (ND and ID groups) improved (p < 0.05) those parameters compared to the unsupplemented groups (N and I groups). Inhibited nuclear factor erythroid 2-related factor 2 (Nrf2)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α (PGC-1α) activity resulted in decreased redox status, skeletal muscle structural damage, skeletal muscle mitochondrial function impairment, and decreased performance in IUGR newborns. Supplementation of DMG-Na in sow milk activated the Nrf2/SIRT1/PGC-1α in IUGR newborns, thereby improving their skeletal muscle performance.

Dimethylglycine Sodium Salt Alleviates Intrauterine Growth Restriction-Induced Low Growth Performance, Redox Status Imbalance, and Hepatic Mitochondrial Dysfunction in Suckling Piglets.

This study aimed to investigate the mechanism of redox status imbalance and hepatic mitochondrial dysfunction induced by intrauterine growth restriction (IUGR) and relieve this condition through dimethylglycine sodium salt (DMG-Na) supplementation during the suckling period. Thirty normal birth weight (NBW) and 30 IUGR newborns were selected from 20 sows. Briefly, 1 NBW and 1 IUGR newborn were obtained from each litter of 10 sows, and 10 NBW and 10 IUGR newborns were obtained. Additionally, 2 NBW and 2 IUGR newborns were obtained from each litter of another 10 sows, and 20 NBW newborns were allocated to the N [basic milk diets (BMDs)] and ND (BMDs+0.1% DMG-Na) groups. Furthermore, 20 IUGR newborns were assigned to the I (BMDs) and ID (BMDs+0.1% DMG-Na) groups. The results revealed that the growth performance, serum and hepatic redox status, and hepatic gene and protein expression levels were lower (P < 0.05) in the I group compared to the N group. Additionally, supplementation with DMG-Na (ND and ID groups) improved (P < 0.05) these parameters compared to the non-supplemented groups (N and I groups). In conclusion, the activity of Nrf2/SIRT1/PGC1α was inhibited in IUGR newborns, and this led to their hepatic dysfunctions. Supplementation with DMG-Na activated Nrf2/SIRT1/PGC1α in IUGR newborns, thereby improving their performance.

Dimethylglycine sodium salt activates Nrf2/SIRT1/PGC1α leading to the recovery of muscle stem cell dysfunction in newborns with intrauterine growth restriction

The objectives of this study were focused on the mechanism of mitochondrial dysfunction in skeletal muscle stem cells (MuSCs) from intrauterine growth restriction (IUGR) newborn piglets, and the relief of dimethylglycine sodium salt (DMG-Na) on MuSCs mitochondrial dysfunction by Nrf2/SIRT1/PGC1α network. In this study, six newborn piglets with normal birth weight (NBW) and six IUGR newborn piglets were slaughtered immediately after birth to obtain longissimus dorsi muscle (LM) samples. MuSCs were collected and divided into three groups: MuSCs from NBW newborn piglets (N), MuSCs from IUGR newborn piglets (I), and MuSCs from IUGR newborn piglets with 32 μmol DMG-Na (ID). Compared with the NBW group, the IUGR group showed decreased (P < 0.05) serum and LM antioxidant defense capacity, and increased (P < 0.05) serum and LM damage. Compared with the N group, the I group showed decreased (P < 0.05) MuSCs antioxidant defense capacity, mitochondrial ETC complexes, energy metabolites, and antioxidant defense-related and mitochondrial function-related gene and protein expression levels. The antioxidant defense capacity, mitochondrial ETC complexes, energy metabolites, and antioxidant defense-related and mitochondrial function-related gene and protein expression levels of MuSCs were improved (P < 0.05) in the ID group compared to those in the I group. The MuSCs of IUGR newborns activate the Nrf2/SIRT1/PGC1α network by taking in DMG-Na, thereby neutralizing excessive generated O2•− that may help to improve their unfavorable mitochondrial dysfunction in skeletal muscle.

Intrauterine growth restriction neonates present with increased angiogenesis through the Notch1 signaling pathway

Intrauterine growth restriction (IUGR) is associated with increased perinatal mortality and morbidity, and plays an important role in the development of adult cardiovascular diseases. This study brings forward a hypothesis that Human umbilical vein endothelial cells (HUVECs) from IUGR newborns present dysfunctions and varying changes of signaling pathways as compared to the Control group. Similar pathways may also be present in pulmonary or systemic vasculatures. HUVECs were derived from newborns. There were three groups according to the different fetal origins: normal newborns (Control), IUGR from poor maternal nutrition (IUGR1), and pregnancy-induced hypertension (IUGR2). We found that IUGR-derived HUVECs showed a proliferative phenotype compared to those from normal subjects. Interestingly, two types IUGR could cause varying degrees of cellular dysfunction. Meanwhile, the Notch1 signaling pathway showed enhanced activation in the two IUGR-induced HUVECs, with subsequent activation of Akt or extracellular signal regulated protein kinases1/2 (ERK1/2). Pharmacological inhibition or gene silencing of Notch1 impeded the proliferative phenotype of IUGR-induced HUVECs and reduced the activation of ERK1/2 and AKT. In summary, elevated Notch1 levels might play a crucial role in IUGR-induced HUVECs disorders through the activation of ERK1/2 and AKT. These pathways could be potential therapeutic targets for prevention of the progression of IUGR associated diseases later in life.

“Postnatal Growth of Intrauterine Growth Restricted Newborns”

Introduction: Intrauterine growth restriction plays a significant role in short and long term adverse outcome. It is reflected in the relatively high incidence of neurodevelopmental impairment and somatic growth failure. Growth in the first year of life gets an opportunity to recover its growth deficit of intrauterine life and to catch up with its normal birth weight siblings Objective of the Study: To assess the postnatal growth of intrauterine growth restricted newborns at 3, 6 and 9 months of age. Methodology: A Prognostic cohort study was conducted at Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh from 1st April 2017 to 20th September 2018. It involved monitoring of 31 intrauterine growth restricted newborns and 39 normal birth weight neonates over a period of 9 months. Follow up were done at 3, 6 and 9 month of age. At every visit weight, length, occipitofrontal circumference and chest circumference were measured. Data was analyzed using SPSS 20 and plotted in tables and graphs. Data imputation was done for the missing data. Multiple regression analysis was done for confounder of growth when data was statistically significant. Results: Mean birth weight were 1748 ±437.09 g and 2893.54±467.07g, birth length 44 ±4.2439 cm and 49.26±1.634cm, birth occipitofrontal circumference 30.76 ±2.380 cm and 34.35±1.083cm, birth chest circumference 24.39 ±1.940 cm and 29.15±2.933cm in IUGR and control group respectively which was statistically significant. There were catch-up weight gain in 3, 6 and 9 months of age in IUGR group but it was less than the normal birth weight group during the followed-up period. During the follow-up period, cacth up growth in length achieved in first 9 months of age. During the first 3 months there were no catch up growth in IUGR babies head circumference but it increases in normal rates. Mean chest circumference values at 3 months were statistically significant and after multiple regression analysis, it is significant for birth length. In general, IUGR babies when compared with the control group remained small in all the four growth parameters but it had catch up growth in first 9 months of age. Conclusion: During the follow-up period, catch-up of growth achieved regarding weight, length, OFC and chest circumference but the growth parameters were lower than the appropriate for gestational age birth weight newborns

The Acute Hepatic NF-κB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice.

Intrauterine growth restriction (IUGR) is a relevant predictor for higher rates of neonatal sepsis worldwide and is associated with an impaired neonatal immunity and lower immune cell counts. During the perinatal period, the liver is a key immunological organ responsible for the nuclear factor kappa B (NF-κB)-mediated innate immune response to inflammatory stimuli, but whether this role is affected by IUGR is unknown. Herein, we hypothesized that the newborn liver adapts to calorie-restriction IUGR by inducing changes in the NF-κB signaling transcriptome, leading to an attenuated acute proinflammatory response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic gene expression of key NF-κB factors in the IUGR and normally grown (NG) newborn mice. Real-time quantitative PCR (RT-qPCR) analysis revealed an upregulation of both IκB proteins genes (Nfkbia and Nfkbib) and the NF-κB subunit Nfkb1 in IUGR vs. NG. We next measured the LPS-induced hepatic expression of acute proinflammatory genes (Ccl3, Cxcl1, Il1b, Il6, and Tnf) and observed that the IUGR liver produced an attenuated acute proinflammatory cytokine gene response (Il1b and Tnf) to LPS in IUGR vs. unexposed (CTR). Consistent with these results, LPS-exposed hepatic tumor necrosis factor alpha (TNF-α) protein concentrations were lower in IUGR vs. LPS-exposed NG and did not differ from IUGR CTR. Sex differences at the transcriptome level were observed in the IUGR male vs. female. Our results demonstrate that IUGR induces key modifications in the NF-κB transcriptomic machinery in the newborn that compromised the acute proinflammatory cytokine gene and protein response to LPS. Our results bring novel insights in understanding how the IUGR newborn is immunocompromised due to fundamental changes in NF-κB key factors.

Late-onset intrauterine growth restriction and HHV-6 infection: A pilot study.

Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections havingbeen associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition.

Ouabain Protects Nephrogenesis in Rats Experiencing Intrauterine Growth Restriction and Partially Restores Renal Function in Adulthood.

Intrauterine growth restriction (IUGR) is, in general, accompanied by a reduction of the nephron number, which increases the risk of hypertension and renal dysfunction. Studies have revealed that ouabain can partially restore the number of nephrons during IUGR. However, there is limited information regarding the melioration of nephric structure and function. We used maternal malnutrition to induce an IUGR model in rats. Subsequently, we used a mini-pump to administer ouabain to IUGR rats during pregnancy. Male offspring were divided randomly into two groups. One group was fed a normal diet, whereas the other was fed an isocaloric 8% high-salt diet. Maternal malnutrition led to a reduction in the birth weight and number of nephrons in offspring. At the end of a 40-week follow-up period, offspring from the IUGR group had high blood pressure and abnormal excretion of urinary protein; these parameters were exacerbated in offspring fed a high-salt diet. However, ouabain administration during pregnancy could partially restore the number of nephrons in IUGR offspring, normalize blood pressure, and reduce urinary protein excretion, even when challenged with a high-salt diet. Pathology findings revealed that IUGR, particularly following feeding of a high-salt diet, damaged the ultrastructure of glomeruli, but these harmful effects were ameliorated in offspring treated with ouabain. Collectively, our data suggest that ouabain could rescue nephrogenesis in IUGR newborns and protect (at least in part) the structure and function of the kidney during adulthood even when encountering unfavorable environmental challenges in subsequent life.

Expression of e-NOS in Human Placentas of Idiopathic Intra Uterine Growth Restriction at Term

Endothelial nitric oxide synthase (e-NOS) is a chemical agent that involves in placental angiogenesis. It is conveyed through embryogenesis. In the contemporary study, we intended to examine the character of placental angiogenesis in the progress of intrauterine growth restriction (IUGR) by means of matching the levels of expression of e-NOS in normal-term pregnancy and IUGR placentas. Angiogenesis is one dominant factor in normal embryogenesis and hence the wellbeing of the newborn. The expression of e-NOS was planned using the streptavidin-biotin-peroxidase technique in placental tissues identified as normal (n = 33) and IUGR (n = 33) cases from mothers looking apparently normal. All were chosen at term pregnancy and obtained between 2nd of February of 2018 and 31th of January 2019 at selected hospitals. Outcomes were appraised semi-quantitatively. The expression of e-NOS marker as an immunohistochemistry total score and staining percentage were significantly greater (p &lt; 0.05) in epithelial surface, smooth muscle cells of fetal vessels and the connective tissue terminal villous core of the IUGR placentas when matched with placentas collected from normal pregnancies at term. Encountered placental histochemical changes regarding the expression of the e-NOS angiogenic factor for idiopathic IUGR newborns raised the suspicion of that, it was caused by pure placental factors and could represent further requirement for Nitric Oxide to dilate fetal vessels to optimize functional requirement during placental insufficiency. The noticed Increased expression of e-NOS may be the result of inadequate uteroplacental perfusion supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR

Intrauterine Growth Restriction: New Insight from the Metabolomic Approach.

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn’s short- and long-term health. Ever since the first suggestion of the “thrifty phenotype hypothesis” in the last decade of the 20th century, a number of studies have confirmed the association between low birth weight and cardiometabolic syndrome later in life. During intrauterine life, the growth-restricted fetus makes a number of hemodynamic, metabolic, and hormonal adjustments to cope with the adverse uterine environment, and these changes may become permanent and irreversible. Despite advances in our knowledge of IUGR newborns, biomarkers capable of identifying this condition early on, and stratifying its severity both pre- and postnatally, are still lacking. We are also still unsure about these babies’ trajectory of postnatal growth and their specific nutritional requirements with a view to preventing, or at least limiting, long-term complications. In this setting, untargeted metabolomics—a relatively new field of ‘-omics’ research—can be a good way to investigate the metabolic perturbations typically associated with IUGR. The aim of this narrative review is to provide a general overview of the pathophysiological and clinical aspects of IUGR, focusing on evidence emerging from metabolomic studies. Though still only preliminary, the reports emerging so far suggest an “early” pattern of glucose intolerance, insulin resistance, catabolite accumulation, and altered amino acid metabolism in IUGR neonates. Further, larger studies are needed to confirm these results and judge their applicability to clinical practice.

Intrauterine Growth Restriction: Transsectoral, Interdisciplinary and Multiprofessional Care for Pregnant Women and Newborns in a Feto-neonatal Pathway: A Project of the Innovationsfonds

Intrauterine growth restriction (IUGR) is present in fetuses that do not achieve their full in-utero growth potential. IUGR needs to be discriminated from small for gestational age (SGA) because IUGR newborns in particular experience long-term side effects from their small growth. IUGR fetuses have a significantly increased risk of prematurity and a distinct risk profile compared to adequate-for-gestational-age preterm newborns. Complications of prematurity are more frequent, including bronchopulmonary dysplasia, intraventricular hemorrhage, and meconium ileus. IUGR newborns are at risk of long-term health issues like cerebral palsy, impaired lung function, and delayed speech development. Interdisciplinary and interprofessional care of IUGR pregnancies in the context of a standardized health care research project is feasible: Pregnant women at risk are identified, early therapy with acetylsalicylic acid is started as indicated, risk-adapted care at level III centers is organized including psychosocial interventions and neonatal consultations. Postnatally, integrated neonatal care focusing on parent-child interaction and optimized nutrition is a hallmark. Afterwards, in-depth pediatric follow-up visits with local pediatricians help to identify growth and neurodevelopment problems early. The effects, acceptance. and cost efficiency of this approach are evaluated prospectively as part of an Innovationsfonds project.

Cardiac left heart morphology and function in newborns with intrauterine growth restriction: relevance for long-term assessment.

To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction(IUGR) pregnancies. A cohort of IUGR infants were evaluated by serial echocardiographies at deliveryand at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the controlgroup according to gestational age (AGA). Left heart measurements were significantly lower in IUGR newbornscompared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004). IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates.

Neuropathology in intrauterine growth restricted newborn piglets is associated with glial activation and proinflammatory status in the brain

BackgroundThe fetal brain is particularly vulnerable to intrauterine growth restriction (IUGR) conditions evidenced by neuronal and white matter abnormalities and altered neurodevelopment in the IUGR infant. To further our understanding of neurodevelopment in the newborn IUGR brain, clinically relevant models of IUGR are required. This information is critical for the design and implementation of successful therapeutic interventions to reduce aberrant brain development in the IUGR newborn. We utilise the piglet as a model of IUGR as growth restriction occurs spontaneously in the pig as a result of placental insufficiency, making it a highly relevant model of human IUGR. The purpose of this study was to characterise neuropathology and neuroinflammation in the neonatal IUGR piglet brain.MethodsNewborn IUGR (< 5th centile) and normally grown (NG) piglets were euthanased on postnatal day 1 (P1; < 18 h) or P4. Immunohistochemistry was utilised to examine neuronal, white matter and inflammatory responses, and PCR for cytokine analysis in parietal cortex of IUGR and NG piglets.ResultsThe IUGR piglet brain displayed less NeuN-positive cells and reduced myelination at both P1 and P4 in the parietal cortex, indicating neuronal and white matter disruption. A concurrent decrease in Ki67-positive proliferative cells and increase in cell death (caspase-3) in the IUGR piglet brain was also apparent on P4. We observed significant increases in the number of both Iba-1-positive microglia and GFAP-positive astrocytes in the white matter in IUGR piglet brain on both P1 and P4 compared with NG piglets. These increases were associated with a change in activation state, as noted by altered glial morphology. This inflammatory state was further evident with increased expression levels of proinflammatory cytokines (interleukin-1β, tumour necrosis factor-α) and decreased levels of anti-inflammatory cytokines (interleukin-4 and -10) observed in the IUGR piglet brains.ConclusionsThese findings suggest that the piglet model of IUGR displays the characteristic neuropathological outcomes of neuronal and white matter impairment similar to those reported in the IUGR human brain. The activated glial morphology and elevated proinflammatory cytokines is indicative of an inflammatory response that may be associated with neuronal damage and white matter disruption. These findings support the use of the piglet as a pre-clinical model for studying mechanisms of altered neurodevelopment in the IUGR newborn.

Identificación de restricción del crecimiento intrauterino tardío con doppler umbilical normal mediante algoritmo diagnóstico multiparámetro en el Instituto Nacional Materno Perinatal

Objetivos. Identificar Neonatos con Restricción del Crecimiento Intrauterino (RCIU) Tardío con doppler umbilical normal y evaluar el valor diagnóstico anteparto de un algoritmo multiparámetro. Materiales y métodos. Estudio analítico, observacional y retrospectivo y creación más evaluación preliminar de una prueba diagnóstica. Fueron seleccionados al azar 96 neonatos de 35 a 41 semanas sin anomalías. 23 Pequeños para la Edad Gestacional (PEG) según el método local de clasificación del crecimiento, 13 con peso adecuado para la edad gestacional (AEG) limítrofe (dentro de los 200 g sobre el percentil 10) y 60 con peso AEG sobre el percentil 25. Se identificaron 22 casos de RCIU (casos) y 74 no RCIU (controles) según una definición operativa pre establecida. Los valores estadísticos fueron calculados para pruebas diagnósticas simples con Epidat 3,1. Resultados. 22 de 96 neonatos(23 % ) fueron clasificados como RCIU; 16 de los 23 PEG (69,5 %); 6 de 13 AEG con peso limítrofe ( 46,2 %) y 0 de 60 AEG con peso mayor al percentil 25. La sensibilidad, especificidad, VPP, VPN, CP + y CP – global fue de 86,4 %; 95,9 %; 86,4 %; 95,9 %; 21,3 y 0,14 respectivamente. Sólo 4 de 22 (18%) casos de RCIU fueron diagnosticados como tal en el anteparto a diferencia de 19 de 22 ( 86,4 % ) mediante el uso del algoritmo diagnóstico. Conclusiones. El uso de un algoritmo diagnóstico multiparámetro mejora la identificación de RCIU en ≥ 35 semanas con doppler umbilical normal.