Intrauterine Growth Restriction Infants Research Articles

Thrombopoietin exerts a neuroprotective effect by inhibiting the suppression of neuronal proliferation and axonal outgrowth in intrauterine growth restriction rats

Chronic hypoxia in utero causes intrauterine growth restriction (IUGR) of the fetus. IUGR infants are known to be at higher risk for neurodevelopmental disorders, but the mechanism is unclear. In this study, we analyzed the structure of the cerebral cortex using IUGR model rats generated through a reduced uterine perfusion pressure operation. IUGR rats exhibited thinner cerebral white matter and enlarged lateral ventricles compared with control rats. Expression of neuron cell markers, Satb2, microtubule-associated protein (MAP)-2, α-tubulin, and nestin was reduced in IUGR rats, indicating that neurons were diminished at various developmental stages in IUGR rats, from neural stem cells to mature neurons. However, there was no increase in apoptosis in IUGR rats. Cells positive for Ki67, a marker of cell proliferation, were reduced in neurons and all glial cells of IUGR rats. In primary neuron cultures, axonal elongation was impaired under hypoxic culture conditions mimicking the intrauterine environment of IUGR infants. Thus, in IUGR rats, chronic hypoxia in utero suppresses the proliferation of neurons and glial cells as well as axonal elongation, resulting in cortical thinning and enlarged lateral ventricles. Thrombopoietin (TPO), a platelet growth factor, inhibited the decrease in neuron number and promoted axon elongation in primary neurons under hypoxic conditions. Intraperitoneal administration of TPO to IUGR rats resulted in increases in the number of NeuN-positive cells and the area coverage of Satb2. In conclusion, suppression of neuronal proliferation and axonal outgrowth in IUGR rats resulted in cortical thinning and enlargement of lateral ventricles. TPO administration might be a novel therapeutic strategy for treating brain dysmaturation in IUGR infants.

Uteroplacental insufficiency decreases leptin expression and impairs lung development in growth-restricted newborn rats.

The study aimed to analyze the effect of uteroplacental insufficiency (UPI) on leptin expression and lung development of intrauterine growth restriction (IUGR) rats. On day 17 of pregnancy, time-dated Sprague-Dawley rats were randomly divided into either an IUGR group or a control group. Uteroplacental insufficiency surgery (IUGR) and sham surgery (control) were conducted. Offspring rats were spontaneously delivered on day 22 of pregnancy. On postnatal days 0 and 7, rats' pups were selected at random from the control and IUGR groups. Blood was withdrawn from the heart to determine leptin levels. The right lung was obtained for leptin and leptin receptor levels, immunohistochemistry, proliferating cell nuclear antigen (PCNA), western blot, and metabolomic analyses. UPI-induced IUGR decreased leptin expression and impaired lung development, causing decreased surface area and volume in offspring. This results in lower body weight, decreased serum leptin levels, lung leptin and leptin receptor levels, alveolar space, PCNA, and increased alveolar wall volume fraction in IUGR offspring rats. The IUGR group found significant relationships between serum leptin, radial alveolar count, von Willebrand Factor, and metabolites. Leptin may contribute to UPI-induced lung development during the postnatal period, suggesting supplementation as a potential treatment. The neonatal rats with intrauterine growth restriction (IUGR) caused by uteroplacental insufficiency (UPI) showed decreased leptin expression and impaired lung development. UPI-induced IUGR significantly decreased surface area and volume in lung offspring. This is a novel study that investigates leptin expression and lung development in neonatal rats with IUGR caused by UPI. If our findings translate to IUGR infants, leptin may contribute to UPI-induced lung development during the postnatal period, suggesting supplementation as a potential treatment.

Immediate Outcome of Intrauterine Growth Restricted Infants

Background: Intrauterine growth restriction (IUGR) is one of the major public health issues in developing countries like Bangladesh. IUGR has got significant importance due to its approach towards post neonatal, infant and childhood mortality and morbidity. Objective: To identify immediate outcome of IUGR infants. Methods: This case control study was conducted in department of Neonatology at BSMMU, Dhaka from August 2015 to July 2016, where 98 newborns in the NICU during study period were the study population. All the IUGR babies were labeled as case (Group- A), n=49 and the babies of the same gestational age were labeled as control (Group-B), n=49. The outcome was observed by the caution and careful NICU follow up of the baby. After collection, data were entered into a personal computer and were edited, analyzed, plotted in graphs and tables. Data were analyzed by chi square test, Mann Whitney U tests, using the statistical package for social sciences (SPSS) version 20. P values less than 0.05 (95% CI) were considered statistically significant. Result: During the study in case group, hypoglycemia (p=0.007) & hyperbilirubinemia (P=<0.001) were statistically significant complication. Length of hospital stay was more (P=0.001) in IUGR group which was also significant. Death was more in IUGR than AGA group. Conclusion: From our result, we can conclud e that Hypoglycemia and hyperbilirubinemia were significant complication of IUGR babies. IUGR babies had longer hospital stay than AGA babies. Death were more in IUGR babies but was not statistically significant. Sir Salimullah Med Coll J 2023; 31: 9-12

Effects of Intrauterine Growth Restriction (IUGR) on Growth and Body Composition Compared to Constitutionally Small Infants.

(1) Intrauterine growth restriction (IUGR) is associated with multiple morbidities including growth restriction and impaired neurodevelopment. Small for gestational age (SGA) is defined as a birth weight <10th percentile, regardless of the etiology. The term is commonly used as a proxy for IUGR, but it may represent a healthy constitutionally small infant. Differentiating between IUGR and constitutionally small infants is essential for the nutritional management. (2) Infants born at <37 weeks of gestation between 2017 and 2022, who underwent body composition measurement (FFM: fat-free mass; FM: fat mass) at term-equivalent age, were included in this study. Infants with IUGR and constitutionally small infants (SGA) were compared to infants appropriate for gestational age (AGA). (3) A total of 300 infants (AGA: n = 249; IUGR: n = 40; SGA: n = 11) were analyzed. FFM (p < 0.001) and weight growth velocity (p = 0.022) were significantly lower in IUGR compared to AGA infants, but equal in SGA and AGA infants. FM was not significantly different between all groups. (4) The FFM Z-score was significantly lower in IUGR compared to AGA infants (p = 0.017). Being born constitutionally small compared to AGA had no impact on growth and body composition. These data showed that early aggressive nutritional management is essential in IUGR infants to avoid impaired growth and loss of FFM.

Assessment of Infantile Psychomotor Development Status in 6 and 12-Month-Old IUGR Infants: A Historical Cohort Study

Intrauterine growth restriction (IUGR) is responsible for different post-natal adverse outcomes. This study aimed to evaluate the post-natal psychomotor development status in 6 and 12-month-old IUGR infants who received early preventive interventions. A historical cohort study was done at an Iranian Hospital (2019). The case group included one-year-old infants with a history of IUGR at birth. This group was visited every 2 months to evaluate their growth and neurodevelopmental status. Their parents had also received some training to improve their infant's sensory and motor skills. The control group comprised one-year-old healthy infants with a history of appropriate for gestational age (AGA) at birth. Data related to psychomotor developmental indices based on the ASQ questionnaire at 6 and 12-month for both groups was extracted from subjects' records. Infants' psychomotor development status was compared between groups. Forty-one infants with a history of IUGR and 43 healthy control infants were included in this study. There were significant differences between 2 groups associated with abnormalities in all evaluated psychomotor skills, including gross motor (P=0.014), problem-solving ability (P=0.049), communication (P=0.031), fine motor (P=0.016) and personal-social (P=0.016) at 6 months. After one year of family-based interventions for the case group, significant differences between groups were notable in only fine motor (P=0.016) and personal-social skills (P=0.031). At 12 months, the psychomotor disorders related to gross motor, problem-solving ability, and communication were significantly alleviated in the IUGR group. Early preventive family-based interventions can improve the neurodevelopmental outcomes in 12-month-old IUGR infants.

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 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.

Comparing neonatal outcome of late preterm: Intrauterine growth restricted (IUGR) average for gestational age infants

Comparing Neonatal outcome of late preterm -Intrauterine growth restricted (IUGR) vs Average for Gestational age (AGA) infants.Background: Individuals who had IUGR experience a range of poorer developmental outcomes, encompassing cognitive, socioemotional, and behavioral domains, compared with individuals who were born appropriate for gestational age (AGA).The primary aim was to evaluate neonatal outcome in late preterm IUGR and SGA infants and comparing them.Methods: Out of 3256 total live births, late preterm births are 341(10.4%). Incidence of IUGR in late preterm infants is 71/341(2.15%) and AGA is 170/341(8.25%). We analysed 100 singleton pregnancies, 50 infants with birth weight less than 10th percentile, control group with 50 infants with birth weight between 11-89 percentile at 34-36+6 weeks gestational age. The control group consisted of spontaneous preterm delivery at the same gestational age.Birth weight percentiles were based on the standard growth curve of Alexander et al. Results: There was a significant difference in mean birth weight between the two groups (IUGR: 1720g and AGA: 2495g). The frequency of cesarean sections was 64% in the IUGR group and 26% in the AGA group. 3 neonates of the IUGR group and one of the AGA infants presented Apgar scores <7 at 5 minutes. The length of stay of the newborn in the nursery, as well as the need for and duration of hospitalization in the NICU, differed significantly between the two groups. TTN, Neonatal sepsis and hyperbilirubinemia didnot differ between groups but phototherapy required for IUGR group is more.Conclusion: Late-preterm IUGR infants present a significantly higher risk of neonatal complications and a significantly longer NICU and hospital stay when compared to late-preterm AGA infants.

Stereological and histopathological assessment of intrauterine growth restriction placenta from Saudi women

BackgroundPlacental insufficiency causes fetal adaptation, leading to fetal programming of chronic diseases. Placentas with intrauterine growth restriction (IUGR) are smaller than average and may contribute to low birth weight of the newborn. The number of patients with IUGR in the Saudi population is increasing; however, little is known about their placentas. The aim of this study was to assess morphometric and histopathological placental changes in Saudi patients with IUGR. MethodsOverall, 20 healthy pregnant Saudi women (control group) and 20 pregnant Saudi women with IUGR were enrolled. Maternal and fetal morphometric measurements were recorded. The placentas from both groups were processed for histopathological examination using stereological techniques. ResultsThe IUGR group had lower placental weight, volume, length, breadth, and surface area than the control group. The total volume of villi and surface area of the terminal villi were significantly reduced in the IUGR placentas. IUGR group had a reduction in birth weight; length; and circumference of the head, chest, abdomen, and thigh compared to control group. ConclusionThe reduction in placental mass, specifically the reduction in the volume and surface area of villi, the functional units, may have reduced the capacity for nutrient transport. This led to a significant reduction in neonatal measurements. The fetus rearranged nutrient distribution in favor of the brain and other essential organs; however, at the expense of thigh development and growth. This fetal trade-off strategy increases the risk of developing chronic diseases in adulthood. Therefore, IUGR infants may require more clinical attention.

Association between Prenatal Maternal Tobacco Use and Intrauterine Growth Restriction: A Case-Control Study

Introduction: Intrauterine growth restriction (IUGR) refers to the poor growth of a baby while in the mother’s womb during pregnancy. More than 9% of women smoke tobacco and one-third of women consume smokeless tobacco in developing countries. The intent of the study was to examine the effect on fetal intrauterine growth retardation using maternal tobacco. Methods: This convenient case-control study was conducted with 75 cases and 150 suitably matched controls enrolled in the Department of Pediatrics at Sylhet MAG Osmani Medical College Hospital for about 12 months. Ethical considerations were undertaken before the enrollment of patients. Data were analyzed using SPSS software. Result: ST user mothers of IUGR infants used jarda or gul as smokeless tobacco about 5 times a day and smoker mothers smoked about 5 sticks a day. Maternal tobacco use had a higher (6.9 times) risk of having IUGR babies compared to the non-tobacco user. Conclusion: This study observed that maternal total tobacco use showed a risk of having IUGR infants more than 6.9 times in contrast to non-tobacco user.

Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case-control study.

The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth. Neonates born <32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case-control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses. Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis. Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease. Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth. Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates. This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR. New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine.

Preweaning performance in intrauterine growth-restricted piglets: Characteristics and interventions.

Intrauterine growth restriction (IUGR) is frequently observed in pig production, especially when using highly prolific sows. IUGR piglets are born with low body weight and shape indicative of differences in organ growth. Insufficient uteroplacental nutrient transfer to the fetuses is the leading cause of growth restriction in the pig. Supplementing the sow's gestation diet with arginine and/or glutamine improves placenta growth and functionality and consequently is able to reduce IUGR incidence. IUGR piglets are at higher risk of dying preweaning and face higher morbidity than their normal-weight littermates. A high level of surveillance during farrowing and individual nutrient supplementation can reduce the mortality rates. Still, these do not reverse the long-term consequences of IUGR, which are induced by persistent structural deficits in different organs. Dietary interventions peri-weaning can optimize performance but these are less effective in combating the metabolic changes that occurred in IUGR, which affect reproductive performance later in life. IUGR piglets share many similarities with IUGR infants, such as a poorer outcome of males. Using the IUGR piglet as an animal model to further explore the structural and molecular basis of the long-term consequences of IUGR and the potential sex bias could aid in fully understanding the impact of prenatal undernutrition and finding solutions for both species and sexes.

Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR).

In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup’s whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3′,5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies.

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.

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.

Body Composition of Infants Born with Intrauterine Growth Restriction: A Systematic Review and Meta-Analysis.

Intrauterine growth restriction (IUGR) may predispose metabolic diseases in later life. Changes in fat-free mass (FFM) and fat mass (FM) may explain this metabolic risk. This review studied the effect of IUGR on body composition in early infancy. Five databases and included studies from all countries published from 2000 until August 2021 were searched. Participants were IUGR or small-for-gestational age (SGA) infants, and the primary outcomes were FFM and FM. Eighteen studies met the inclusion criteria, of which seven were included in the meta-analysis of primary outcomes. Overall, intrauterine growth-restricted and SGA infants were lighter and shorter than normal intrauterine growth and appropriate-for-gestational age infants, respectively, from birth to the latest follow up. They had lower FFM [mean difference −429.19 (p = 0.02)] and FM [mean difference −282.9 (p < 0.001)]. The issue of whether lower FFM and FM as reasons for future metabolic risk in IUGR infants is intriguing which could be explored in further research with longer follow-up. This review, the first of its kind can be useful for developing nutrition targeted interventions for IUGR infants in future.

Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS): study protocol for a double-blind, randomized, placebo-controlled parallel clinical trial of n-3 polyunsaturated fatty acids in pregnant smokers

BackgroundTobacco use during pregnancy is the most important modifiable risk factor associated with adverse pregnancy outcomes, increasing the risk of preterm birth, intrauterine growth restriction and sudden infant death syndrome. Fewer than half of pregnant smokers can quit on their own. Identifying safe and effective therapies to prevent tobacco-related adverse pregnancy outcomes and/or increase smoking cessation in pregnant women would have a substantial public health impact. Cigarette smoking is associated with a relative deficiency in circulating n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) levels. A recent analysis found that smokers taking n-3 LCPUFAs during pregnancy had a reduction in preterm labor risk when compared to non-smokers. Studies have shown that supplemental n-3 LCPUFAs may also reduce nicotine cravings and daily cigarette use. Thus, smokers may benefit from supplemental n-3 LCPUFAs by lowering the risk of preterm labor and/or increased smoking cessation. To address important remaining knowledge gaps, we propose the Investigating N-3 Fatty Acids to prevent Neonatal Tobacco related outcomeS (INFANTS).MethodsThe INFANTS study is a multicenter, randomized, double-blind, placebo-controlled study that will randomize 400 pregnant smokers to either supplemental n-3 LCPUFAs or placebo. Participants will be enrolled between 12 and 24 weeks’ gestation and followed until 6 weeks after delivery. We will recruit from clinical centers throughout Middle Tennessee. We will assess smoking behavior after 12 weeks of supplementation using self-report and validated biomarkers of tobacco exposure. We will measure response to supplementation using biological markers of n-3 LCPUFA status. Our primary endpoint will be preterm labor as reflected by gestational age at delivery. Our secondary endpoint will be change from baseline in cigarettes per day at 12 weeks.DiscussionThis study tests the hypothesis that smoking-induced n-3 LCPUFA deficiencies contribute to tobacco-related adverse pregnancy outcomes and that supplementation of n-3 LCPUFAs in pregnant smokers may prevent these complications. If our study demonstrates that supplemental n-3 LCPUFAs are effective at reducing the risk of tobacco-related adverse neonatal outcomes and/or reducing tobacco use during pregnancy, our results could have an immediate and major impact on pregnancy care and neonatal outcomes.Trial registrationClinicalTrials.gov NCT04417595. Registered on April 21, 2020

Alteration in 11 Beta-Hydroxysteroid Dehydrogenase Type-2 (HSD11B2) Gene as A Potential Candidate Parameter for Early Detection of Intrauterine Growth Restriction (IUGR) Events

Intrauterine Growth Restriction (IUGR) incidence in Indonesia ranks in the top 10 of the highest in Asia. It is the main perinatal death cause. IUGR also impairs fetal neurodevelopment, which can affect the development of children until later ages. Lack of 11β-hydroxysteroid dehydrogenase type-2 (11β-HSD2) enzyme is influenced by changes in the coding gene, HSD11B2, one of IUGR's causes. The main diagnostic method of IUGR at this time is by using Doppler ultrasound. However, Doppler ultrasound has several limitations as many cases are not detected. Its clinical predictive value in various women is poor, as Doppler ultrasound is not recommended for use in the first trimester, detection of abnormalities in the second trimester seems to be too late for helpful interventions. The study aim is to present an overview concerning HSD11B2 gene alteration in an non-invasive prenatal testing (NIPT) as a possible diagnostic parameter for early detection in IUGR infants. This literature review is based on selected articles and studies taken from the Pubmed, Proquest, and EBSCO databases. A total of 4 studies reported the tendency for DNA methylation and decreased expression of the HSD11B2 gene in IUGR cases. Changes in the HSD11B2 gene have the potential to become a diagnostic parameter in the early detection of infants with IUGR. Further study and investigation of this possibility are needed.Keywords: intrauterine growth restriction, HSD11B2, early detection, diagnostic, non-invasive prenatal testing