Impact Of Intrauterine Growth Restriction Research Articles

233 Exploring the impact of intrauterine growth restriction on fecal microbiota and metabolome in pigs

Abstract Intrauterine growth restriction (IUGR) poses a significant challenge in swine production, affecting approximately 20% of piglets and resulting in increased mortality rates, metabolic disturbances, compromised intestinal development, and altered microbial colonization. This phenomenon arises as the IUGR fetus adapts to limited oxygen and nutrient supply in utero by reallocating blood flow towards vital organs, particularly the brain, consequently leading to a greater brain-to-liver weight ratio (BrW/LW) at birth. Our study aimed to comprehensively investigate the repercussions of IUGR on fecal microbiota composition and plasma metabolome profiles in pigs from birth through to slaughter. To elucidate these effects, we conducted computed tomography scans on piglets within 24 h of birth to assess brain and liver weights accurately. Subsequently, we selected two groups of piglets based on the BrW/LW. Specifically, 12 piglets with the greatest BrW/LW (IUGR; BrW/LW: 1.00 ± 0.09) and 12 with the least BrW/LW (NORM; BrW/LW: 0.36 ± 0.04). From these piglets we collected fecal and blood samples at specific time points: during lactation (T1: d 16 ± 0.6), after the starter period (T2: d 63 ± 8.6), and at the onset (T3: d 119 ± 11.4) and conclusion (T4: d 162 ± 14.3) of the finisher period. Throughout the study, all pigs received identical diets to eliminate dietary confounders. In the lactation, starter and grower but not finisher period, IUGR piglets grew 47, 19 and 14% slower, respectively compared with their NORM littermates. Our findings revealed that fecal microbial α-diversity remained unaffected by IUGR across all time points examined, indicating a stable microbial richness within the gut microbiota of IUGR and NORM pigs. However, β-diversity, reflecting inter-group microbial community variation, exhibited significant differences at T1 (P = 0.002), T2 (P = 0.079), and T3 (P = 0.027), suggesting distinct microbial compositions between IUGR and NORM pigs at these stages. Specifically, IUGR pigs displayed a greater abundance of Clostridium sensu stricto 1 and Romboutsia at T1, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Alloprevotella at T2, and p-2534-18B5 gut group at T3. Conversely, the NORM group exhibited increased concentrations of Ruminococcus at T1, HT002 at T2, and Prevotella_9 at T3. Furthermore, while plasma metabolite analysis revealed no significant differences between IUGR and NORM pigs at T1, decreased arginine levels were observed in the IUGR group compared with NORM at T2 (P < 0.05). In conclusion, our study underscores the profound and persistent impact of IUGR on fecal microbiota composition in pigs from birth to the initial stages of the finisher period, while suggesting minimal alterations in the blood metabolome profile throughout various growth stages. These findings provide valuable insights into the long-term consequences of IUGR on swine health and production. This research received funding from the European Union’s Horizon 2020 research and innovation program under a Marie Sklodowska-Curie grant (agreement no. 955374).

Thriving or Striving: Comparing Intra-Uterine Growth Restricted, Low Birth Weight and Normal Birth Weight Piglets within the First 24 Hours.

This observational study explored the early-life challenges of intra-uterine growth restricted (IUGR), low birth body weight (LBW), and normal birth body weight (NBW) piglets. The aim was to understand the impact of birth weight and intra-uterine growth restriction phenotype on neonatal survival and behavior. Based on weight and phenotype, piglets were classified as IUGR (n = 32), LBW (n = 34), and NBW (n = 29) immediately after birth. The piglets were litter- and sex-matched. Vitality scores were assigned based on motor activity and breathing and complemented with an assessment of umbilical cord condition, rectal temperature, crown-rump length (CRL), time to reach the udder, time to suckle, colostrum intake, and weight gain over 24 h. Beyond the lower birth weight, reduced CRL, and higher mortality rate, IUGR piglets faced several other challenges compared with LBW and NBW piglets. Growth-impaired piglets often struggled to engage in early feeding behaviors and displayed consistently lower rectal temperatures at 1, 3 and 24 h after birth. IUGR piglets showed inadequate colostrum intake and weight loss, which were also observed for LBW counterparts. In contrast, no significant differences were observed in vitality scores and umbilical cord conditions across the groups. In conclusion, our findings underscore the impact of intra-uterine growth restriction on neonatal piglets, emphasizing the need for specialized care strategies to improve survival and health outcomes in IUGR.

Disentangling the link between maternal influences on birth weight and disease risk in 36,211 genotyped mother–child pairs

Epidemiological studies have robustly linked lower birth weight to later-life disease risks. These observations may reflect the adverse impact of intrauterine growth restriction on a child’s health. However, causal evidence supporting such a mechanism in humans is largely lacking. Using Mendelian Randomization and 36,211 genotyped mother-child pairs from the FinnGen study, we assessed the relationship between intrauterine growth and five common health outcomes (coronary heart disease (CHD), hypertension, statin use, type 2 diabetes and cancer). We proxied intrauterine growth with polygenic scores for maternal effects on birth weight and took into account the transmission of genetic variants between a mother and a child in the analyses. We find limited evidence for contribution of normal variation in maternally influenced intrauterine growth on later-life disease. Instead, we find support for genetic pleiotropy in the fetal genome linking birth weight to CHD and hypertension. Our study illustrates the opportunities that data from genotyped parent-child pairs from a population-based biobank provides for addressing causality of maternal influences.

The impact of intrauterine growth restriction and prematurity on nephron endowment.

In humans born at term, maximal nephron number is reached by the time nephrogenesis is completed - at approximately 36 weeks' gestation. The number of nephrons does not increase further and subsequently remains stable until loss occurs through ageing or disease. Nephron endowment is key to the functional capacity of the kidney and its resilience to disease; hence, any processes that impair kidney development in the developing fetus can have lifelong adverse consequences for renal health and, consequently, for quality and length of life. The timing of nephrogenesis underlies the vulnerability of developing human kidneys to adverse early life exposures. Indeed, exposure of the developing fetus to a suboptimal intrauterine environment during gestation - resulting in intrauterine growth restriction (IUGR) - and/or preterm birth can impede kidney development and lead to reduced nephron endowment. Furthermore, emerging research suggests that IUGR and/or preterm birth is associated with an elevated risk of chronic kidney disease in later life. The available data highlight the important role of early life development in the aetiology of kidney disease and emphasize the need to develop strategies to optimize nephron endowment in IUGR and preterm infants.

Impact of Intrauterine Growth Restriction and Placental Insufficiency on Nutritional Outcomes of Extremely Low Birth Weight Infants.

Introduction The aim of our study was to assess the impact of intrauterine growth restriction (IUGR) and placental insufficiency (PI) on the nutritional outcomes of extremely low birth weight (ELBW) infants. Methods We conducted a six-year retrospective case-control study that included 117 ELBW infants. Of these, 58 infants had IUGR and 59 were born appropriate-for-gestational age (AGA). Infants with IUGR were further divided based on the presence or absence of PI, as determined by umbilical arterial doppler velocimetry on serial ultrasounds. Results IUGR infants with PI had the lowest enteral calorie intake at 28 days of life (DOL) (median intake- IUGR+PI: 32 vs IUGR-PI: 93 vs AGA: 110 kcal/kg/day; p-value 0.011) and at 36 weeks corrected gestational age (CGA) (median intake- IUGR+PI: 102 vs IUGR-PI: 125 vs AGA: 119 kcal/kg/day; p-value 0.012). These infants also trended towards requiring a longer duration of total parenteral nutrition (TPN) (median duration - IUGR+PI: 35 vs IUGR-PI: 25 vs AGA: 21 days; p-value 0.054) and higher incidence of conjugated hyperbilirubinemia (IUGR+PI: 43% IUGR-PI: 29% vs AGA: 16%; p-value 0.058), but these results did not reach statistical significance. Despite challenges with enteral nutrition, IUGR infants with PI showed good catch-up growth and had higher growth velocities over the first month of life, compared to AGA controls. Conclusion IUGR in the presence of PI is associated with significantly poorer enteral nutritional outcomes in ELBW infants. However, with the support of optimal parenteral nutrition these infants showed good catch-up growth.

Impact of intrauterine growth restriction on cerebral and renal oxygenation and perfusion during the first 3 days after birth

Intrauterine growth restriction (IUGR) is associated with a higher incidence of perinatal complications as well as cardiovascular and renal diseases later on. A better insight into the disease mechanisms underlying these sequalae is important in order to identify which IUGR infants are at a higher risk and find strategies to improve their outcome. In this prospective case–control study we examined whether IUGR had any effect on renal and cerebral perfusion and oxygen saturation in term neonates. We integrated near-infrared spectroscopy (NIRS), echocardiographic, Doppler and renal function data of 105 IUGR infants and 105 age/gender-matched controls. Cerebral and renal regional oxygen saturation values were measured by NIRS during the first 12 h after birth. Echocardiography alongside Doppler assessment of renal and anterior cerebral arteries were performed at 6, 24, 48 and 72 h of age. Glomerular and tubular functions were also assessed. We found a left ventricular dysfunction together with a higher cerebral oxygen saturation and perfusion values in the IUGR group. IUGR term infants showed a higher renal oxygen saturation and a reduced oxygen extraction together with a subclinical renal damage, as indicated by higher values of urinary neutrophil gelatinase-associated lipocalin and microalbumin. These data suggest that some of the haemodynamic changes present in growth-restricted foetuses may persist postnatally. The increased cerebral oxygenation may suggest an impaired transition to normal autoregulation as a consequence of intra-uterine chronic hypoxia. The higher renal oxygenation may reflect a reduced renal oxygen consumption due to a subclinical kidney damage.

Assessment of the impact of Intrauterine Growth Restriction on Gastrointestinal Tract Tolerance to Nutrition in Very Low Birth Weight Neonates at Zagazig University Hospital

Assessment of the impact of Intrauterine Growth Restriction on Gastrointestinal Tract Tolerance to Nutrition in Very Low Birth Weight Neonates at Zagazig University Hospital

Going Up Inflame: Reviewing the Underexplored Role of Inflammatory Programming in Stress-Induced Intrauterine Growth Restricted Livestock.

The impact of intrauterine growth restriction (IUGR) on health in humans is well-recognized. It is the second leading cause of perinatal mortality worldwide, and it is associated with deficits in metabolism and muscle growth that increase lifelong risk for hypertension, obesity, hyperlipidemia, and type 2 diabetes. Comparatively, the barrier that IUGR imposes on livestock production is less recognized by the industry. Meat animals born with low birthweight due to IUGR are beset with greater early death loss, inefficient growth, and reduced carcass merit. These animals exhibit poor feed-to-gain ratios, less lean mass, and greater fat deposition, which increase production costs and decrease value. Ultimately, this reduces the amount of meat produced by each animal and threatens the economic sustainability of livestock industries. Intrauterine growth restriction is most commonly the result of fetal programming responses to placental insufficiency, but the exact mechanisms by which this occurs are not well-understood. In uncompromised pregnancies, inflammatory cytokines are produced at modest rates by placental and fetal tissues and play an important role in fetal development. However, unfavorable intrauterine conditions can cause cytokine activity to be excessive during critical windows of fetal development. Our recent evidence indicates that this impacts developmental programming of muscle growth and metabolism and contributes to the IUGR phenotype. In this review, we outline the role of inflammatory cytokine activity in the development of normal and IUGR phenotypes. We also highlight the contributions of sheep and other animal models in identifying mechanisms for IUGR pathologies.

Unravelling the impact of intrauterine growth restriction on heart development: insights into mitochondria and sexual dimorphism from a non-hominoid primate.

Fetal exposure to an unfavorable intrauterine environment programs an individual to have a greater susceptibility later in life to non-communicable diseases, such as coronary heart disease, but the molecular processes are poorly understood. An article in Clinical Science recently reported novel details on the effects of maternal nutrient reduction (MNR) on fetal heart development using a primate model that is about 94% genetically similar to humans and is also mostly monotocous. MNR adversely impacted fetal left ventricular (LV) mitochondria in a sex-dependent fashion with a greater effect on male fetuses, although mitochondrial transcripts increased more so in females. Increased expression for several respiratory chain and adenosine triphosphate (ATP) synthase proteins were observed. However, fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, likely contributing to a 73% decreased LV ATP content and increased LV lipid peroxidation. Moreover, MNR fetal LV mitochondria showed sparse and disarranged cristae. This study indicates that mitochondria are targets of the remodeling and imprinting processes in a sex-dependent manner. Mitochondrial ROS production and inadequate energy production add another layer of complexity. Altogether these observations raise the possibility that dysfunctional mitochondria in the fetus may contribute in turn to epigenetic memory of in utero stress in the adult. The role of mitoepigenetics and involvement of mitochondrial and genomic non-coding RNAs in mitochondrial functions and nuclei-mitochondria crosstalk with in utero stress awaits further investigation.

Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease

Introduction: Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial respiratory impairment if subsequently exposed to an allergen. This study used a maternal hypoxia-induced mouse model of IUGR to determine the combined effects of IUGR and allergy on airway responsiveness.Methods: Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11-GD 17.5 (IUGR group; term = GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). All offspring were sensitized to ovalbumin (OVA) and assigned to one of four treatment groups: Control – normoxic and saline challenge; IUGR – hypoxic and saline challenge; Allergy – normoxic and OVA challenge; and IUGR + Allergy – hypoxic and OVA challenge. At 8 weeks of age, and 24 h post-aerosol challenge, mice were tracheostomised for methacholine challenge and assessment of lung mechanics by the forced oscillation technique, and lungs subsequently fixed for morphometry.Results: IUGR offspring were lighter than Control at birth and in adulthood. Both Allergy and IUGR independently increased airway resistance after methacholine challenge. The IUGR group also exhibited an exaggerated increase in tissue damping and elastance after methacholine challenge compared with Control. However, there was no incremental effect on airway responsiveness in the combined IUGR + Allergy group. There was no impact of IUGR or Allergy on airway structure and no effect of sex on any outcome.Conclusion: IUGR and aeroallergen independently increased bronchoconstrictor response, but when combined the pathophysiology was not worsened. Findings suggest that an association between IUGR and asthma is mediated by baseline airway responsiveness rather than susceptibility to allergen.

Lung function between 8 and 15 years of age in very preterm infants with fetal growth restriction.

The impact of intrauterine growth restriction (IUGR) on lung function in very preterm children is largely unknown as current evidence is mainly based on studies in children born small for gestational age but not necessarily with IUGR. Spirometry, transfer factor of the lung for carbon monoxide (TLco), and lung clearance index (LCI) were cross-sectionally evaluated at 8.0-15.0 years of age in children born <32 weeks of gestation with IUGR (n = 28) and without IUGR (n = 67). Controls born at term (n = 67) were also included. Very preterm children with IUGR had lower mean forced expired volume in the first second (FEV1) z-score than those with normal fetal growth (∆ -0.66, 95% confidence interval (CI) -1.12, -0.19), but not significant differences in LCI (∆ +0.24, 95% CI -0.09, 0.56) and TLco z-score (∆ -0.11, 95% CI -0.44, 0.23). The frequency of bronchopulmonary dysplasia (BPD) in the two groups was, respectively, 43% and 10% (P = 0.003). IUGR was negatively associated with FEV1 (B = -0.66; P = 0.004), but the association lost significance (P = 0.05) when adjusting for BPD. IUGR has an impact on conducting airways function of very preterm children at school age, with part of this effect being mediated by BPD. Ventilation inhomogeneity and diffusing capacity, instead, were not affected. IUGR does not necessarily imply a low birthweight for gestational age (and vice versa). While a low birthweight is associated with worse respiratory outcomes, the impact of IUGR on lung function in premature children is largely unknown. IUGR affects conducting airways function in school-age children born <32 weeks with IUGR, but not ventilation inhomogeneity and diffusing capacity. The impact of IUGR on FEV1 seems mainly related to the higher risk of BPD in this group.

The impact of intrauterine growth restriction on cytochrome P450 enzyme expression and activity

With the increased prevalence of non-communicable disease and availability of medications to treat these and other conditions, a pregnancy free from prescribed medication exposure is rare. Up to 99% of women take at least one medication during pregnancy. These medications can be divided into those used to improve maternal health and wellbeing (e.g., analgesics, antidepressants, antidiabetics, antiasthmatics), and those used to promote the baby's wellbeing in either fetal (e.g., anti-arrhythmics) or postnatal life (e.g., antenatal glucocorticoids). These medications are needed for pre-existing or coincidental illnesses in the mother, maternal conditions induced by the pregnancy itself through to conditions that arise in the fetus or that will be encountered by the newborn. Thus, medications administered to the mother may be used to treat the mother, the fetus or both. Metabolism of medications is regulated by a range of physiological processes that change during pregnancy. Other pathological processes such as placental insufficiency can in turn have both immediate and lifelong adverse health consequences for babies. Individuals born growth restricted are more likely to require medications but may also have an altered ability to metabolise these medications in fetal and postnatal life. This review aims to determine the effect of suboptimal fetal growth on the fetal expression of the drug metabolising enzymes (DMEs) that convert medications into active or inactive metabolites, and the transporters that remove both these medications and their metabolites from the fetal compartment.

Hydrocortisone and bronchopulmonary dysplasia: variables associated with response in premature infants.

ObjectiveThe primary objective was to evaluate hydrocortisone’s efficacy for decreasing respiratory support in premature infants with developing bronchopulmonary dysplasia (BPD). Secondary objectives included assessment of the impact of intrauterine growth restriction (IUGR), maternal history of chorioamnionitis, side effects and route of administration associated with hydrocortisone’s efficacy. Dexamethasone as second-line treatment to decrease respiratory support was reviewed.MethodsRetrospective chart review of preterm infants requiring respiratory support receiving hydrocortisone.ResultsA total of 48 patients were included. Successful extubation was achieved in 50% of intubated patients after hydrocortisone treatment with no major complications. In our small study, history of maternal chorioamnionitis, IUGR or route of administration did not affect the response. Rescue dexamethasone after hydrocortisone therapy was ineffective in the ten patients who failed extubation following hydrocortisone.ConclusionHydrocortisone is effective in decreasing respiratory support in patients with developing BPD without major complications. Randomized studies are warranted to confirm our findings.

Membrane proteomic analysis reveals the intestinal development is deteriorated by intrauterine growth restriction in piglets.

The alterations of the intestinal proteome were observed in intrauterine growth restriction (IUGR) piglets during early life by gel-based approaches. Nevertheless, how IUGR affects the intestinal membrane proteome during neonatal development remains unclear. Here, we applied the iTRAQ-based proteomics technology and biochemical analysis to investigate the impact of IUGR on the membrane proteome of the jejunal mucosa in the piglets. Three hundred sixty-one membrane proteins were screened by functional prediction. Among them, eight, five, and one differentially expressed membrane proteins were identified between IUGR and NBW piglets at day 0, day 7, and day 21 after birth, respectively. Differentially expressed membrane proteins (DEMPs) including F1SBL3, F1RRW8, F1S539, F1S2Z2, F1RIR2, F1RUF2 I3LP60, Q2EN79, and F1SIH8 were reduced while the relative abundance of I3L6A2, F1SCJ1, F1RI18, I3LRJ7, and F1RNN0 were increased in IUGR piglets than NBW piglets. From the aspects of function, F1RRW8, F1S539, F1S2Z2, and F1RIR2 are mainly associated with D2 dopamine receptor binding, transmembrane transport of small molecules, signal transduction, and translocation of GLUT4, respectively, and F1SIH8, I3LRJ7, and F1RNN0 are related to autophagy, metabolism of vitamins, and intracellular protein transport. Additionally, IUGR decreased the level of proteins (F1RRW8, Q2EN79, and F1RI18) that are involved in response to oxidative stress.

The impact of intrauterine growth restriction on adiposity and small intestine morphology during postnatal development in pigs

The impact of intrauterine growth restriction on adiposity and small intestine morphology during postnatal development in pigs

Impact of Intrauterine Growth Restriction on the Capillarization of the Early Postnatal Rat Heart.

Capillarization plays a key role in the growth of the developing heart. We therefore hypothesized that impaired heart development following intrauterine growth restriction (IUGR) may arise from inadequate myocardial capillary growth. The aims of the study were to examine the effect of IUGR on the growth and diffusion radius of intramyocardial capillaries in rats at postnatal day 1. Uteroplacental insufficiency was induced in rats in late gestation (E18, term = E22) by bilateral uterine artery and vein ligation (restricted offspring N = 12; six males and six females); offspring from sham-operated dams were used as controls (N = 10; five males and five females). At postnatal day 1, the hearts were immersion-fixed and heart volume, capillary length density, capillary diffusion radius, and total capillary length were stereologically determined. Restricted offspring were significantly smaller at birth, with a concomitant reduction in heart volume and total myocardial capillary length compared to controls. Capillary growth was not impaired relative to heart size, with no significant differences in capillary length density or diffusion radius in the myocardium of restricted and control offspring. There were no sex differences in any of the parameters examined. In conclusion, there was no evidence to indicate that microvascular development is compromised in the heart of IUGR offspring at 1 day after birth. Total myocardial capillary length, however, was significantly reduced in the growth restricted offspring and further longitudinal studies are required to elucidate the long-term impact, particularly following hypertrophic cardiac growth. Anat Rec, 302:1580-1586, 2019. © 2018 American Association for Anatomy.

Impact of Intrauterine Growth Restriction on Cognitive and Motor Development at 2 Years of Age.

Intrauterine growth restriction (IUGR), which is already known to be a risk factor for pathological intrauterine development, perinatal mortality, and morbidity, is now also assumed to cause both physical and cognitive alterations in later child development. In the current study, effects of IUGR on infantile brain function were investigated during the fetal period and in a follow-up developmental assessment during early childhood. During the fetal period, visual and auditory event-related responses (VER and AER) were recorded using fetal magnetoencephalography (fMEG). VER latencies were analyzed in 73 fetuses (14 IUGR fetuses) while AER latencies were analyzed in 66 fetuses (11 IUGR fetuses). Bayley Scales of Infant Development, Second Edition (BSID-II) were used to assess the developmental status of the infants at the age of 24 months. The Mental Development Index (MDI) was available from 66 children (8 IUGR fetuses) and the Psychomotor Development Index (PDI) from 63 children (7 IUGR fetuses). Latencies to visual stimulation were more delayed in IUGR than in small for gestational age (SGA) or appropriate for gestational age (AGA) fetuses, albeit not to any significant extent (p = 0.282). The MDI in former IUGR infants was significantly lower (p = 0.044) than in former SGA and AGA infants. However, IUGR had no impact on PDI (p = 0.213). These findings support the hypothesis that IUGR may constitute a risk factor for neurodevelopmental delay. Further investigation of the possible underlying mechanisms, as well as continued long-term developmental research, is therefore necessary.

Impact of intrauterine growth restriction and birth weight on infant's early childhood neurodevelopment outcome

Background: Infants with intrauterine growth restriction (IUGR) are at increased risk of perinatal morbidity and mortality in addition to long-term neurodevelopmental impairment due to fetal, placental, or maternal causes. Aim: This study aims to evaluate early childhood neurodevelopmental outcome from 18 to 24 months of age following a pregnancy complicated by IUGR. Study Design: This is an observational cohort study of prospectively collected data from a neonatal follow-up program (NFP) at the King Khalid University Hospital, Riyadh, Saudi Arabia. Results: A total of 65 IUGR infants with a median gestational age (GA) of 36 weeks (28–40 weeks) and a median birth weight of 1595 g (740–2280 g) were enrolled in the NFP. The majority of the mothers were Saudi 63 (97%), with a mean age of 30 years (19–45 years). Sixty-five percent of the infants were born by cesarean section. The prevalence of IUGR was 5.5% with predominance of symmetrical IUGR pattern 52 (80%). The median age of developmental assessment was 15 months (7–33 months). Thirty-two infants (49.2%) had a lower score (moderate 23 (35.4%) and severe 9 (13.4%) by Bayley Infant Neurodevelopmental Screening (BINS). There were no correlations between BINS category and birth weight, GA, gender, or type of IUGR. Catch-up growth was achieved in 44 (66.7%) of the infants at a median age of 9 months. Conclusion: We have demonstrated a higher incidence of poor neurodevelopmental scores at the early ages from 15 to 24 months among infants who were born following a pregnancy complicated by IUGR. BINS scores were not influenced by birth weight, GA, gender, or type of IUGR. IUGR is an independent variable for poor neurodevelopmental outcome. These patients will be followed to preschool ages for further neurocognitive assessment.

The impact of IUGR on pancreatic islet development and β-cell function.

Placental insufficiency is a primary cause of intrauterine growth restriction (IUGR). IUGR increases the risk of developing type 2 diabetes mellitus (T2DM) throughout life, which indicates that insults from placental insufficiency impair β-cell development during the perinatal period because β-cells have a central role in the regulation of glucose tolerance. The severely IUGR fetal pancreas is characterized by smaller islets, less β-cells, and lower insulin secretion. Because of the important associations among impaired islet growth, β-cell dysfunction, impaired fetal growth, and the propensity for T2DM, significant progress has been made in understanding the pathophysiology of IUGR and programing events in the fetal endocrine pancreas. Animal models of IUGR replicate many of the observations in severe cases of human IUGR and allow us to refine our understanding of the pathophysiology of developmental and functional defects in islet from IUGR fetuses. Almost all models demonstrate a phenotype of progressive loss of β-cell mass and impaired β-cell function. This review will first provide evidence of impaired human islet development and β-cell function associated with IUGR and the impact on glucose homeostasis including the development of glucose intolerance and diabetes in adulthood. We then discuss evidence for the mechanisms regulating β-cell mass and insulin secretion in the IUGR fetus, including the role of hypoxia, catecholamines, nutrients, growth factors, and pancreatic vascularity. We focus on recent evidence from experimental interventions in established models of IUGR to understand better the pathophysiological mechanisms linking placental insufficiency with impaired islet development and β-cell function.

The impact of intrauterine growth restriction on respiratory outcomes.

Intrauterine growth restriction (IUGR) is caused by fetal growth below what is normal for its genetic potential. Recent studies have shown a distinct association between changes in umbilical artery flow in IUGR subjects and an increased risk of respiratory morbidity and consequently, higher mortality. The aim of this study was to find the impact of IUGR on the respiratory outcomes of premature neonates born with less than 32 weeks gestational age. This retrospective cohort study targeted infants born with less than 32 weeks of gestation, admitted at NCIU, between January 2010 and December 2016. Each selected IUGR case was matched according to gestational age and sex with an appropriate birthweight newborn at a 1:2 ratio, within a 12-month period. The study involved 126 neonates, 42 with IUGR, and 84 control subjects. IUGR was not identified as a predictor of Bronchopulmonary Dysplasia (BDP) (OR 4.80, 95% CI: 1.14-20.21, P=0.033). Abnormal umbilical artery flow (OR 4.80, 95% CI: 1.14-20.21, P=0.033) and late onset sepsis (OR 3.31, 95% CI: 1.04-10.56, P=0.044) were significantly associated with BDP. It is essential to recognize changes in the umbilical artery flow, especially in high-risk pregnancies such as IUGR, since these represent an a priori risk marker for the development of BDP. The individual and combined effect of IUGR, alterations on umbilical artery flow and extreme prematurity has not yet been completely clarified on the impact on lung morbidity, requiring a larger number of studies.