Intrauterine Growth Restriction Neonates Research Articles

Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being "at risk" in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

Hemostatic Profile of Intrauterine Growth-Restricted Neonates: Assessment with the Use of NATEM Assay in Cord Blood Samples.

Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples. During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE). IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT. IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables.

Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial.

UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM. Clinical trial registry of India (CTRI/2021/03/031864). •Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC). •An association between UCM and intraventricular hemorrhage in preterm neonates < 28weeks of gestation is still being investigated. •Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates. •UCM also increases the need for non-invasive respiratory support compared to DCC.

Pregnancy outcomes in ANCA-associated vasculitis patients: A systematic review and meta-analysis

ObjectiveAntineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), namely granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis constitute a group of rare systemic vasculitides, affecting small vessels. Genders are equally affected, with symptoms most commonly presenting during and/or after the fifth decade of life, but AAV may also present in younger individuals. As advanced maternal age is becoming common and safe over the last decades, it is now more feasible for middle-aged women suffering from AAV to get pregnant. Although adverse pregnancy outcomes have been thoroughly investigated in other systemic diseases, the exact prevalence of pregnancy complications and unfavorable outcomes in pregnant women with AAV has not been systematically evaluated. MethodsWe researched PubMed, Scopus, Cochrane Library and Cinahl databases until September, 2022. Three blinded investigators extracted data and assessed the risk of bias. A random effects model was used for the analysis. The outcomes studied were pre-term delivery, intrauterine growth restriction (IUGR) neonates and disease flare. ResultsWe included six studies with 92 pregnancies in patients with AAV. The prevalence of pre-term delivery, IUGR neonates and disease flare were 18% (CI: 0.10–0.30, P=non-significant), 20% (CI: 0.11–0.33, P=non-significant) and 28% (CI: 0.09–0.59, P<0.01), respectively. ConclusionThe analysis demonstrated higher occurrence of adverse outcomes in pregnant women suffering from AAV accompanied by an increased risk of disease flare during pregnancy. These findings underline the importance of preconception counseling and the necessity of close monitoring in these patients similarly to other systemic inflammatory diseases.

Early versus Late Enteral Feeding in Preterm Intrauterine Growth Restricted Neonates with Antenatal Doppler Abnormalities

Background: Placental insufficiency and decreased placental nutrition transfer from the mother to the fetus are the underlying causes of intra-uterine growth restriction (IUGR), a serious and very frequent issue in the perinatal period. Due to a lack of recent research in the area, the current study aims to compare the outcomes of two different feeding strategies for preterm infants with abnormal Doppler readings: early vs. delayed initiation of enteral feeds. Then we implement the better of the two feedings regimens into our standard clinical practice. Objective: The objective of the study was to compare early and late enteral feeding in preterm intrauterine growth restricted neonate to evaluate time to reach full feed, risk of feed Intolerance, weight gain at 10th day of life and length of hospital stays. Study Design: The Randomized Control Trial. Settings: This study was conducted in the neonatology department Tertiary Care Hospital (Nursery MCH Centre, Pakistan Institute of Medical Sciences, Islamabad Pakistan. Duration: 1st June 2022 to 1st December 2022. Methods: The sample was collected from the by non-probability consecutive sampling technique. Babies of any sex who meet the requirements during the first 72 hours of life. A total of 80 newborns were recruited out of them n=40 infants were found as early feeding and n=40 was assigned to late feeding. Demographic and baseline information (admission date, age, gender, gestational age, birth weight) of enrolled neonates recorded in the prescribed proforma. Effects of early or late feeding were monitored daily for 10 days. The outcomes in terms of time to reach full feed, weight gain at 10th day of life and feed intolerance were recorded and compared in both groups. All the information entered on the predesigned proforma by the researcher himself to comply with the study protocol attached. Results: A total of 80 newborns were recruited out of them n=40 infants were found as early feeding and n=40 was assigned to late feeding. The base line characteristics including birth weight, gestational age, respiratory support etc. were not statistically significant. Also, there is no difference of NEC (0.267) and FI (0.312) in early and late feeding groups. The Cox regression HR: 1.21 (95% CI: 0.829-3.72); p = 0.326). In both groups, the early feeding arm had a shorter median duration by 7 days. Further, the data was compared between early and late feeding group to determined which group is quicker for discontinuation of PN. Conclusion: Our study finds that using the feeding initiation and advancement method and AREDF on Doppler with exclusive breast milk results in faster PN cessation and does not increase the incidence of NEC or FI in preterm IUGR infants between 27 and 33 weeks of age.

Proposal to expand the definition of intrauterine growth restriction and introduce two new screening methods

The authors of this publication have developed a new screening method to evaluate the physical development of infants, which identifies growth and developmental restrictions based on their gestational age, gender, weight and length standard positions and nourishment status. This so-called MDN-method (MDN = Maturity, Development, Nourishment) offers several benefits: 1. It enables the expansion of the scope and definition of intrauterine growth restriction (IUGR) and the establishment of five separate condition subtypes. 2. It facilitates the study of the risk of mortality of infants based on their development and nourishment status. 3. The method is suitable for the screening of high-risk IUGR infants and neonates. 4. The MDN method allowed for the development of a new ultrasound screening methodology for high-risk IUGR infants and neonates, based on abdominal circumference (AC) and femur length (FL) standards, which correlate the most with the weight and length of the fetus. The data of 1,244,918 Hungarian live and stillbirths recorded during 2000-2012 were used for these studies. It is believed that these new screening methods may have a significant impact on reducing the frequency of IUGR-related stillbirth and infant mortality cases.

The correlation between stress response term babies with intrauterine growth restriction and adulthood disease theories.

Every year, 14 million babies are born with low birth weight (LBW) and/or intrauterine growth restriction (IUGR) in developing countries. In Sudan, 15-25% of all newborns are born with LBW, with half being Term-LBW. The importance of nutrition in the first 1000 days of life has been well demonstrated. Evidence links IUGR to various health and developmental disorders, and intrauterine programming of the hypothalamic-pituitary-adrenal (HPA) axis has been strongly suggested as a possible mechanism. Sudan has been listed among the lowest four countries regarding food security which has a massive impact on maternal and infant health. We hypothesize that infants who suffer from intrauterine growth retardation will have exaggerated physiological and behavioural responses to physical stressors. To compare T-LBW with T-NBW on (a) Salivary cortisol level at rest and after a physical stressor and (b) Behavioural response to physical stressors. Hospital-based matched case-control study. Cases were 65 T-LBW neonates, and controls were 67 T-NBW neonates matched for age 4-6 hours, gestational age, and mode of deliverymeasurements: Anthropometry, salivary samples for cortisol before and after heel prick, and behavioural ratings. Compared with controls, the IUGR neonates were lighter, shorter, and thinner (p <0.0001) and had lower basal cortisol levels (p <0.03). Following stressors, IUGR neonates had lower (p >0.0001) and inhibited cortisol response (p <0.02), and cried less vigorously (p <0.0001). All anthropometric measures were significantly and positively correlated with behavioural responses and pre- and post-stress cortisol levels. Stunting was more strongly associated with behavioural inhibition than wasting. The severity of intrauterine growth retardation correlated with behavioral and physiological inhibition, which can lead to the development of mismatch diseases such as allergies, autoimmune diseases, and conjunctive disorders.

Intrauterine Growth-Restricted Piglets Are Predisposed to Develop Metabolic Disorders in Adulthood When Fed With Parenteral Nutrition in the Neonatal Period

ObjectivesTotal parenteral nutrition (TPN) is lifesaving yet non-normal nutrition regimen during the neonatal period. However, studies have shown that TPN feeding early in life can permanently alter metabolism at later ages. Moreover, intrauterine growth restricted (IUGR) neonates also have a higher risk of developing metabolic diseases (such as obesity and dyslipidemia) in later life. Because a substantial proportion of IUGR neonates receive TPN in early life, we wondered if the metabolic effects of feeding TPN early in life would exacerbate these effects of IUGR? We hypothesized that feeding TPN to IUGR neonates would aggravate the risk of developing obesity and dyslipidemia in adulthood.MethodsSixteen normal weight female piglets (7 d old) were randomized to sow-fed (SF) or early TPN (TPN-CON); 8 (IUGR or runt) piglets were fed TPN as a third group (TPN-IUGR). After 2 weeks of TPN or suckling, all pigs were fed a normal grower diet for 8 mo. At 8 mo, catheters were implanted and in vivo metabolic tests were conducted.ResultsTPN-IUGR pigs demonstrated catch-up growth by 4 mo, and body weights were not different among groups at 8 mo. The metabolic effects of feeding TPN persisted into adulthood, as indicated by higher postprandial plasma triglycerides (TG) and fasting plasma non-esterified fatty acids (NEFA), compared to SF (P < 0.05). IUGR exacerbated TPN-induced risk for diseases by worsening obesity outcomes with greater subcutaneous fat deposition (P < 0.05) and greater ectopic TG deposition in the liver (P < 0.05) and muscle (P < 0.05). Furthermore, IUGR led to dyslipidemia as indicated by higher cholesterol in fasted plasma LDL (P < 0.05), slower postprandial TG clearance (P < 0.05), higher fasting plasma NEFA (P < 0.001) and higher plasma dimethylglycine (P < 0.05), compared to the TPN-CON. IUGR pigs had greater VLDL secretion, as suggested by higher microsomal transfer protein mRNA (P < 0.05). Early TPN programmed reduced lipogenesis, as indicated by lower fatty acid synthase mRNA (P < 0.05), compared to SF.ConclusionsCollectively, these findings conclude that although TPN is a lifesaving measure, feeding TPN to IUGR neonates has long-term metabolic consequences predisposing them to develop metabolic disorders in adulthood.Funding SourcesCanadian Institutes of Health Research.

Leptin Levels of the Perinatal Period Shape Offspring's Weight Trajectories through the First Year of Age.

Background: Leptin is a hormone regulating lifetime energy homeostasis and metabolism and its concentration is important starting from prenatal life. We aimed to investigate the association of perinatal leptin concentrations with growth trajectories during the first year of life. Methods: Prospective, longitudinal study, measuring leptin concentration in maternal plasma before delivery, cord blood (CB), and mature breast milk and correlating their impact on neonate’s bodyweight from birth to 1 year of age, in 16 full-term (FT), 16 preterm (PT), and 13 intrauterine growth-restricted (IUGR) neonates. Results: Maternal leptin concentrations were highest in the PT group, followed by IUGR and FT, with no statistical differences among groups (p = 0.213). CB leptin concentrations were significantly higher in FT compared with PT and IUGR neonates (PT vs. FT; IUGR vs. FT: p < 0.001). Maternal milk leptin concentrations were low, with no difference among groups. Maternal leptin and milk concentrations were negatively associated with all the neonates’ weight changes (p = 0.017 and p = 0.006), while the association with CB leptin was not significant (p = 0.051). Considering each subgroup individually, statistical analysis confirmed the previous results in PT and IUGR infants, with the highest value in the PT subgroup. In addition, this group’s results negatively correlated with CB leptin (p = 0.026) and showed the largest % weight increase. Conclusions: Leptin might play a role in neonatal growth trajectories, characterized by an inverse correlation with maternal plasma and milk. PT infants showed the highest correlation with hormone levels, regardless of source, seeming the most affected group by leptin guidance. Low leptin levels appeared to contribute to critical neonates’ ability to recover a correct body weight at 1 year. An eventual non-physiological “catch-up growth” should be monitored, and leptin perinatal levels may be an indicative tool. Further investigations are needed to strengthen the results.

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.

Cord Blood Ischemia-Modified Albumin Levels in Preterm Infants with Intrauterine Growth Restriction

Abstract Background Intrauterine growth restriction (IUGR) is one of the causes of perinatal mortality and morbidity. It is the failure of the fetus to achieve intrinsic growth potential. Since IUGR neonates are more likely to suffer complications including perinatal asphyxia, cold stress, hypoglycemia, hypocalcaemia, hyperbilirubinemia, feed intolerance, NEC, sepsis and even mortality. So, it is important that these infants are identified and managed appropriately at birth. Purpose The present study aims to determine the possible association between cord blood ischemia-modified albumin (IMA) levels and intrauterine growth restriction (IUGR) in preterm infants with or without complicated gestations. Patients and Method Eighty mothers and their preterm neonates (&amp;lt;37 weeks’ gestation) identified in 2 groups according to antenatal ultrasound: a group with prospective antenatal diagnosis of IUGR and the other group with normal fetal development, after consideration of inclusion and exclusion criteria. Cord blood Albumin and Ischemia modified albumin were estimated by double-antibody sandwich Enzyme-Linked Immunosorbent Assay (ELISA). Results Cord blood IMA was significantly higher in IUGR group compared to control group. Consequently, albumin level was significantly lower in IUGR group compared to other group. IMA was inversely correlation with Hb level and albumin level was inversely correlated with liver function tests (ALT and AST). Conclusion There is a positive association between IMA level and IUGR. This sent a message that combined antenatal ultrasound and serum IMA is a better predictor of intrauterine growth restriction and subsequent better care of neonates with IUGR.

Apolipoprotein-E Gene Polymorphism and Lipid Composition among IUGR and AGA Neonates.

Objective The objective of this study is to study the profile of apolipoprotein E ( APOE ) gene polymorphism and lipid profile among intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) neonates. This is an observational study. This study was done at the neonatal unit of a teaching hospital in South India. All consecutively born IUGR neonates (cases) of more than 32 weeks' gestational age and AGA neonates (controls) were enrolled for the study. Genomic DNA extraction was done from a total of 102 peripheral venous blood samples. Genotyping of the APOE rs429358 and rs7412 defining the ε2, ε3, and ε4 alleles was done by polymerase chain reaction-restriction fragment length polymorphism method. Prefeed venous blood was collected and analyzed for lipid profile estimation. The allelic frequencies of cases versus control were ε2-9 (8.7%) versus 3 (2.9%); ε3-88 (84.6%) versus 81 (79.4%); and ε4-7 (6.7%) versus 18 (17.6%). The frequency of ε4 isoform allele, associated with adult onset of metabolic diseases was less among the IUGR group. The mean total cholesterol (TC), Low-Density Lipoprotein (LDL), High-Density Lipoprotein, and triglyceride (TG) were 107.59 ± 35.99, 51.69 ± 24.68, 21.75 ± 9.58, and 151.22 ± 61.84 mg/dL, respectively, in the IUGR group. The mean TC and LDL levels in IUGR group were marginally higher than AGA neonates (107 ± 35.99 vs. 100.37 ± 22.69 mg/dL and 51.69 ± 24.68 versus 46.9 ± 19.51 mg/dL, p > 0.05). In both groups, the mean TC and TGL levels were elevated in the ε4 isoform subgroup ( p > 0.05). In our study, the ε2 allele was the second most predominant APOE isoform and the ε4 allele of the APOE gene associated with adult-onset diseases was not increased among IUGR neonates. Neonates with ε4 allele showed an abnormal lipid profile in both study groups suggesting a possible association.

Effects of delayed cord clamping in intrauterine growth-restricted neonates: a randomized controlled trial.

The time of cord clamping in intrauterine growth-restricted (IUGR) neonates remains an area of uncertainty. This assessor-blinded randomized controlled trial compared the effects of delayed cord clamping (DCC) with early cord clamping (ECC) on the systemic blood flow (SBF) and cerebral hemodynamics in IUGR neonates of gestational age ≥28 weeks, not requiring resuscitation. Eligible newborns were randomized to DCC (cord clamping after 60 s; n=55) or ECC (cord clamping within 30 s; n=55) group immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24±2 h. The secondary outcome variables were right ventricular output (RVO), anterior cerebral artery (ACA) blood flow velocity (BFV), superior mesenteric artery (SMA)-BFV and venous hematocrit at 24±2 h, peak total serum bilirubin (TSB), incidences of polycythemia, intraventricular hemorrhage, respiratory distress, feeding intolerance, and necrotizing enterocolitis, outcome, duration of hospital stay, screening audiometry, and serum ferritin levels at the postnatal age of 3 months. Compared to ECC, DCC was associated with significantly higher SVC flow (101.22±21.02 and 81.27±19.12 mL/kg/min, in DCC and ECC groups, respectively; p<0.0001), and significantly increased RVO, SMA-BFV, venous hematocrit, and serum ferritin levels. Though peak TSB was significantly higher with DCC, duration of phototherapy was comparable. ACA-BFV, incidence of polycythemia, and other outcomes were comparable between the groups.Conclusions: DCC was a safe and beneficial intervention in IUGR infants with an improved SBF and SMA-BFV and an increased hematocrit and serum ferritin levels without higher incidences of polycythemia and requirement of phototherapy for significant hyperbilirubinemia.Trial registration: Clinical Trials Registry of India (CTRI/2019/05/018904) What is Known: • Delayed cord clamping (DCC) increases superior vena cava (SVC) blood flow in preterm neonates. • DCC increases hematocrit and serum ferritin in intrauterine growth-restricted (IUGR) neonates, but there may be an associated risk of polycythemia and neonatal hyperbilirubinemia. What is New: • DCC increases SVC blood flow, right ventricular output, superior mesenteric artery blood flow velocity, venous hematocrit, and serum ferritin in IUGR neonates. • Incidences of polycythemia and duration of phototherapy for significant neonatal hyperbilirubinemia do not increase with DCC.

Cardiac Morphology in Neonates with Intrauterine Growth Restriction

Background: Intrauterine growth restriction (IUGR) affects cardiac development. We hypothesized that IUGR impacts early cardiac modelling. Aim: To assess the impact of IUGR on cardiac morphology in premature and term neonates. Study design: Prospective, observational cohort study Subjects: Pregnant women and their neonates with early (week 30+0 -31+6, n=9) and late (week 32+0 -42+0, n=19) IUGR with centralized fetal circulation. A gestational age matched control group (n=41) of non-IUGR neonates with normal prenatal growth and circulation. Outcome measures: Heart size measured by echocardiography. Results: Adjusted for gestational age, birth weight, sex and twin/singleton, IUGR neonates had significantly shorter mean (SEM) left ventricular septum length than non-IUGR neonates (27.8 mm (0.4) vs 29.7 (0.3)), shorter diameter of left atrium (9.4 (0.2) vs 10.8 (0.2)), left ventricle (15.0 (0.3) vs 17.3 (0.2)) and right ventricle (8.3 (0.3) vs 9.9 (0.3)) (p<0.01). In unadjusted estimates, IUGR had more impact on atrial cavities and right ventricle areas and diameters than on longitudinal dimensions, but less impact on atrioventricular valve orifices and left ventricle cavity diameters. This indicated a globular shape of the left ventricle and a symmetrical-to-oblong shape of right ventricle in IUGR. In adjusted estimates, the right ventricle dimensions exhibited an oblong shape whereas left ventricle dimensions were symmetrical. Conclusion: IUGR neonates had smaller hearts compared with non-IUGR neonates. In unadjusted estimates, IUGR hearts portrayed a symmetrical-to-oblong shape of the right ventricle and a globular shape of the left ventricle. In adjusted estimates, right ventricle shape remained oblong, whereas left ventricle shape was symmetrical. Funding Information: The research did not receive any grant from funding agencies in the public, commercial, or not-for-profit sector. Declaration of Interests: None declared. Ethics Approval Statement: The Hospital’s Data Protection Officer and The Regional Ethics Committee of Research, South East, Norway approved the study (2016/923D). The parents gave written informed consent.

HIGHER FREQUENCY OF GERMINAL MATRIX-INTRAVENTRICULAR HEMORRHAGE IN MODERATE AND LATE PRETERM AND EARLY TERM NEONATES WITH INTRAUTERINE GROWTH RESTRICTION COMPARED TO HEALTHY ONES.

SUMMARYGerminal matrix-intraventricular brain hemorrhage is mostly found in preterm neonates, but may also occur in term neonates. The aim of this study was to analyze the prevalence and severity of this type of hemorrhage in moderate and late preterm and early term neonates with intrauterine growth restriction. In the prospective analysis, 100 newborns were examined, i.e. 70 with intrauterine growth restriction and 30 as a control group. Study subjects were neonates from 32 0/7 to 38 6/7 gestational weeks. Body weight, body length, head circumference and ponderal index at birth were analyzed. Hemorrhage was assessed by cranial ultrasound using Papile classification. Out of 70 neonates with intrauterine growth restriction, germinal matrix-intraventricular hemorrhage was not found in 36 (51.43%) neonates, 31 (44.29%) had hemorrhage grade 1, and three (4.29%) had hemorrhage grade 2, which was statistically significant (p<0.001) in relation to the control group. There were no neonates with hemorrhage grade 3 or 4. The predominant type of germinal matrix-intraventricular hemorrhage in the intrauterine growth restriction group was hemorrhage grade 1. Germinal matrix-intraventricular hemorrhage was more often present in the intrauterine growth restricted neonates than in the control group.

Urinary Nerve Growth Factor in full-term, preterm and intra uterine growth restriction neonates: Association with brain growth at 30–40 days of postnatal period and with neuro-development outcome at two years. A pilot study

Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30−40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30−40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.

Effect of Intrauterine Growth Restriction on Cerebral Regional Oxygen Saturation in Preterm and Term Neonates during Immediate Postnatal Transition

Background: Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcome. Affected fetuses commonly display typical blood flow redistribution towards the brain (“brain sparing”). Accordingly, increased cerebral oxygen saturation has been observed in IUGR neonates within the first days of life. Aim: The aim of our study was to assess cerebral oxygenation behavior during immediate neonatal transition in IUGR infants. Methods: This is a retrospective single-center observational cohort study. Cerebral regional oxygen saturation (crSO₂) was measured with near-infrared spectroscopy in neonates during the first 15 min after birth. Neonates with IUGR (IUGR group) were matched for gestational age (±1 week) and gender with neonates that were appropriate for gestational age (AGA). The AGA:IUGR matching ratio was 3:1. Arterial oxygen saturation (SpO₂), heart rate (HR), crSO₂, and cerebral fractional tissue oxygen extraction (cFTOE) were compared between the groups. Results: Between August 2010 and October 2017, 45 neonates with IUGR were identified and matched to 135 AGA neonates. Mean gestational age was 33.1 ± 3.0 weeks in the IUGR group and 33.5 ± 2.7 weeks in the AGA group. Mean birth weight was 1,559 ± 582 g in the IUGR group and 2,051 ± 679 g in the AGA group. There was a significant group difference in crSO₂ beginning at 5 min and continuing for the rest of the observation time with higher crSO₂ values in the IUGR group (main effect group: p = 0.011; interaction time × group: p = 0.039). In cFTOE, a significant difference could be observed at 5–9 and 11–13 min with lower rates of oxygen extraction in the IUGR group (main effect group: p = 0.025; interaction time × group: p = 0.463). Concerning SpO₂ and HR, there was no significant difference between the IUGR and the AGA neonates. Conclusion: Neonates of the IUGR group did show significantly higher crSO₂ values and significantly lower cFTOE values already during immediate neonatal transition compared to the AGA group.

Early sonographic evaluation of the placenta in cases with IUGR: a pilot study.

The objective of this study was to evaluate the feasibility and value of measuring early placental echogenicity to predict fetal intrauterine growth restriction (IUGR). This is a single center, retrospective cohort study. Early ultrasound examination (6 + o to 8 + 6weeks of gestation in singleton pregnancies) was used to measure placental dimensions and placental echogenicity. A ratio between placental echogenicity and myometrial echogenicity (PE/ME-ratio) was calculated for each patient. Study population was assigned to either the IUGR group or the control group based on clinical data. 184 eligible pregnancies were analysed. 49 patients were included in our study. Of those, 9 (18.37%) cases were affected by IUGR and 40 (81.63%) were controls. Measuring the placental echogenicity was feasible in all cases. IUGR neonates had a significant lower placental echogenicity (1.20 (± 0.24) vs. 1.64 (± 0.60), p = 0.033), but no significant differences in the other placental outcomes were observed. Our results showed that measuring placental echogenicity is feasible in the early first trimester and demonstrated a significantly lower placental echogenicity in fetuses with subsequent IUGR. Further prospective studies are needed to validate those results.

The frequency of pulmonary hypertension in newborn with intrauterine growth restriction

Intrauterine growth restriction (IUGR) is a clinical definition applied to neonates born with clinical features of malnutrition and in-utero growth retardation irrespective of their birth weight percentile. This study was aimed to determine the frequency of pulmonary hypertension (PH) in neonates with IUGR. In this descriptive cross-sectional study, we followed 96 neonates with IUGR (≤28 days) and 38 neonates without IUGR born in the department of the neonatal intensive care unit children hospital complex Multan, Pakistan. We analyzed certain factors such as gender, gestational age (GA) (weeks), birth weight (BW in kg), weight percentile (WP) for GA, meconium aspiration syndrome (MAS), birth asphyxia (BA) and respiratory distress syndrome (RDS) for pulmonary hypertension (PH) in IUGR and non-IUGR group. GA was measured by the Ballard scoring system. Echocardiography was performed for all patients by the pediatric cardiologist to measure pulmonary arterial (PA) pressure using Bernoulli’s equation. Out of total 96 IUGR neonates, 33.3% (n = 32) suffered from PH, of which 65.3% (n = 18) were male and 43.7% (n = 14) were female. The percentages of IUGR neonates with BA, MAS and RDS were 34.4%, 18.8% and 22.9% respectively. The data were analyzed using the SPSS-16 software to test the statistical significance of the results. A p-value less than 0.05 was considered significant. When the chi-square test was applied, it depicted that MAS was significantly associated with PH in IUGR neonates (p = 0.0001) compared to non-IUGR neonates. Our findings suggested an increased chance of PH in IUGR neonates and MAS may be a strong factor.

The Relationship of Intrauterine Growth Restriction with Placental Pathologic Changes in Newborns

Introduction: Intrauterine growth restriction is a multifaceted problem and is associated with a significant increase in the level of morbidity and perinatal mortality. According to some studies, failure of the placenta is responsible for the most cases of intrauterine growth restriction. The aim of this study was to evaluate the placental pathologic changes in the intrauterine growth restriction (IUGR) samples and compare them with normal cases.&#x0D; &#x0D; Methods: A study population consisted of 60 intrauterine growth restriction neonates and 60 normalized neonates born at Tehran Imam Khomeini Hospital between June 2016 and July 2017. The placenta was weighed, immediately after delivery, and the umbilical cord was separated, then stored in 10% formalin and sent for pathological examination as soon as possible. Data collection was performed according to the following items: the pathologist's report, the results of the infants' examination, and the data in the neonatal cases.&#x0D; &#x0D; Results: The intrauterine growth restriction group showed a high frequency of placenta infarction (P &lt; 0.001), inflammation of the villous (P &lt; 0.001), villous fibrosis (P = 0.044), villous vascularization disorder (P = 0.001), prevalence of chorioamnionitis (P = 0.027), prevalence of Syncytiotrophoblastic knots (P &lt; 0.001) and placental necrosis (P = 0.048) than normal group. However, the mean weight of the placenta (P &lt; 0.001), the length and width of the macroscopic placenta changes was less (P &lt; 0.001).&#x0D; &#x0D; Conclusion: The results of the current study showed that a major part of the macroscopic and histological changes are detectable in the intrauterine growth restriction samples, which are considerably more common than normal, although they are not pathognomonic, but in the future, more accurate results can be obtained from more extensive studies.