Growth Restricted Neonates Research Articles

Maternal Risk Factors and Perinatal Outcome of Fetal Growth Restriction

Background: Worldwide, Fetal growth restriction is a leading cause of stillbirth, neonatal mortality, and morbidity. Several maternal factors influence fetal growth and increases the risk of fetal growth restriction. Our study aimed to determine the risk factors and perinatal outcome of fetal growth restriction at Tribhuvan University teaching hospital, Maharajgunj, Kathmandu.Methods: A prospective study was conducted in the department of Obstetrics and Gynecology at Tribhuvan University teaching hospital. A total of 140 Pregnant women at > 28 weeks period of gestation clinically diagnosed as FGR and fulfilling the inclusion criteria were enrolled in this study. The data was analyzed using SPSS 23. The association between various risk factors and FGR was studied using the binary logistic regression.Results: Among the 140 FGR fetuses, 27.9 % (39) belonged to the <10th percentile (Mild Fetal growth restriction) and 72.1%(101) belonged to<5th percentile (Severe Fetal growth restriction). Maternal age more than 35 years was found to be statistically significant as a risk factor in the severe Fetal growth restriction group. Among the maternal co-morbidities, hypertensive disorder of pregnancy was found to be the most common co-morbidity followed by heart disease and thyroid disorders. The Fetal growth restriction neonates requiring neonatal intensive care unit (NICU) stay was 42 (30%) and the median neonatal intensive care unit stay was 4 days. The fetal morbidities associated with fetal growth restriction were prematurity,respiratory distress syndrome(RDS), sepsis, meconium aspiration syndrome(MAS) and neonatal jaundice (NNJ). Among the 140 FGR babies, 138 were live born and there were 2 neonatal deaths (NND).Conclusions: In our study ,advanced maternal age is found to be a significant risk factor for Fetal growth restriction and gestational hypertension is the most common comorbidity associated with Fetal growth restriction. Therefore, identification of such women, their regular antenatal checkups, fetal surveillance and timely intervention are crucial for better perinatal outcome.Keywords: Fetal growth restriction, fetal outcome, risk factors.

Maternal vascular indices at 36 weeks' gestation in pregnancy with small or growth-restricted fetus.

To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by delivery of a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate. This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics, medical history, vascular indices and hemodynamic parameters, which were obtained using a non-invasive operator-independent device and included pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. Women with hypertensive disorders of pregnancy were excluded. SGA was diagnosed if birth weight was < 10th percentile. FGR was diagnosed if, in addition to birth weight < 10th percentile, at the 35-37-week scan, uterine artery or umbilical artery pulsatility index (PI) was > 95th percentile or fetal middle cerebral artery PI was < 5th percentile. Among the 6413 women included in the study, there were 605 (9.4%) cases of SGA, 133 (2.1%) cases of FGR and 5675 (88.5%) cases that were unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were increased in the FGR group compared with the unaffected group. Aortic stiffness, as assessed by pulse-wave velocity, and augmentation index did not differ between affected and unaffected pregnancies. In the FGR group, compared with the SGA group, central systolic and diastolic blood pressure were higher, whereas heart rate was lower. SGA and FGR pregnancies exhibit deranged maternal hemodynamic responses compared with unaffected pregnancies. Pregnancies with FGR have higher central blood pressure compared to those with SGA, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Feeding Parenteral Nutrition in the Neonatal Period Programs Dyslipidemia in Adulthood in Yucatan Miniature Pigs

BackgroundEarly nutritional challenges can lead to permanent metabolic changes, increasing risk of developing chronic diseases later in life. Total parenteral nutrition (TPN) is a life-saving nutrition regimen, used especially in intrauterine growth-restricted (IUGR) neonates. Early TPN feeding alters metabolism, but whether these alterations are permanent is unclear. Programmed metabolism is likely caused by epigenetic changes due to imbalances of methyl nutrients. ObjectivesWe sought to determine whether feeding TPN in early life would increase risk of developing dyslipidemia in adulthood and whether supplementing the methyl nutrients betaine and creatine to TPN would prevent this development. We also sought to determine whether IUGR exacerbates the effects of neonatal TPN on lipid metabolism in adulthood. MethodsFemale piglets (n = 32; 7 d old) were used in 4 treatments: 24 normal-weight piglets were randomly assigned to sow-fed (SowFed), standard TPN (TPN-control), and TPN with betaine and creatine (TPN-B+C); 8 IUGR piglets were fed control TPN (TPN-IUGR) as a fourth group. After 2 wk of treatment, all pigs were then fed a standard solid diet. At 8 mo old, central venous catheters were implanted to conduct postprandial fat tolerance tests. ResultsFeeding TPN in the neonatal period led to dyslipidemia in adulthood, as indicated by higher postprandial triglyceride (TG) levels in TPN-control (P < 0.05), compared with SowFed. IUGR piglets were particularly sensitive to neonatal TPN feeding, as TPN-IUGR piglets developed obesity and dyslipidemia in adulthood, as indicated by greater backfat thickness (P < 0.05), higher liver TG (P < 0.05), slower postprandial TG clearance (P < 0.05), and elevated fasting plasma nonhigh-density lipoprotein-cholesterol (P < 0.01), and nonesterified fatty acids (P < 0.001), compared with TPN-control. ConclusionsFeeding TPN in early life increases the risk of developing dyslipidemia in adulthood, especially in IUGR neonates; however, methyl nutrient supplementation to TPN did not prevent TPN-induced changes in lipid metabolism.

The components of arginine and methylarginine metabolism are indicative of altered kidney function in intrauterine growth-restricted neonates.

Intrauterine fetal growth restriction (IUGR) affects up to 10% of all pregnancies. Severe IUGR is associated with impaired kidney development, reduced nephron endowment, and chronic kidney disease later in life. Currently, no early predictive biomarker exists for detecting altered kidney function in neonates with IUGR. Because nephrons produce key enzymes for the metabolism of arginine and methylarginine components, we quantified and compared the concentrations of arginine and methylarginine metabolites between IUGR and non-IUGR neonates to identify potential biomarkers for the early detection of altered kidney function in IUGR neonates. Seventy-one IUGR and 123 non IUGR neonates were examined. Serum and Urine samples were obtained between 30 h and 5 days of life and between 5 and 70 days of life. Serum concentrations of creatinine, urea, symmetric and asymmetric-dimethylarginine metabolites (SDGV, SDMA, ADGV, and ADMA), guanidino-2-oxo-caproic acid (GOCA), citrulline, homocitrulline, arginine, and homoarginine were quantified using LC-MS/MS and standard clinical laboratory methods. Datasets were compared by Mann-Whitney--Wilcoxon or Chi-square tests for continuous and discrete parameters. P values were corrected for multiple comparisons using the Bonferroni method. After Bonferroni correction, we found that serum creatinine, urea, SDGV, ADGV, and GOCA levels were significantly lower in neonates with IUGR. Consequently, the ratios of SDGV/SDMA, ADGV/ADMA, and GOCA/homoarginine were significantly lower in IUGR neonates. Our study suggests that arginine and methylarginine are possible early biomarkers for detecting altered kidney function in IUGR neonates.

Relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine fetal distress

BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries, doctors can more accurately identify fetal intrauterine distress, as well as assess its severity, so that timely interventions can be implemented to safeguard the health and safety of the fetus. AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress. METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups (n = 50 each), according to the presence or absence of intrauterine distress. The ultrasound hemodynamic parameters of the uterine artery (UtA), fetal middle cerebral artery (MCA), and umbilical artery (UmA) were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups. RESULTS Comparison of ultrasonic hemodynamic parameters, resistance index (RI), pulsatility index (PI), and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity (S/D), revealed higher values of fetal MCA, PI, and S/D of UmA in pregnant women with UtA compared to controls (P &lt; 0.05), while there was no difference between the two groups in terms of RI (P &lt; 0.05) The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group (66.7%) than in the control group (90.0%), and neonatal weight (2675.5 ± 27.6 g) was lower than in the control group (3117.5 ± 31.2 g). Further, cesarean section rate was higher in the observation group (70.0%) than in the control group (11.7%), and preterm labor rate was higher in the observation group (40.0%) than in the control group (10.0%). The incidence of fetal distress, neonatal growth restriction and neonatal asphyxia were also higher in the observation group (all P &lt; 0.05). CONCLUSION Fetal MCA, UmA, and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy, which suggests that clinical attention should be paid to them, and monitoring should be strengthened to provide guidance for clinical intervention.

A Growth-Restricted Neonate with Abnormal Facies and Lax Skin.

A Growth-Restricted Neonate with Abnormal Facies and Lax Skin.

L-citrulline Mitigates Systemic Inflammation and Associated Pulmonary Vascular Remodeling in a Neonatal Rat Model of Postnatal Undernutrition

Background &amp; Aim: Preterm infants with postnatal growth restriction and undernutrition are at increased risk of developing bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), metabolic syndrome, and sepsis. Preclinical and clinical studies report increased systemic inflammation, and lung and pancreatic histopathology in growth-restricted neonates. Safe therapies to mitigate these adverse outcomes associated with postnatal growth restriction and undernutrition in preterm infants are needed. L-citrulline is a non-essential amino acid, involved in the urea and nitric oxide cycles, that exhibits anti-inflammatory properties. This study aims to investigate whether L-citrulline may decrease systemic inflammation and improve histopathology in the lung, heart, and pancreas in a neonatal model of postnatal undernutrition. Methods: Neonatal Sprague Dawley rat pups were divided into 2 groups, normal nutrition (litter size n=12) and undernutrition (litter size n=18) by altering the litter size of the nursing dam. Body weight was measured daily and both groups received daily intraperitoneal injections of saline or L-citrulline (2.5g/kg) for 21 days. On postnatal day 21, heart, lung, and pancreatic tissue were collected for histology and mRNA analyses. Lung and pancreatic tissue were processed for qPCR to detect mRNA expression of pro-inflammatory mediators (MCP-1/CCL2, MIP-1α /CCL3, IL-6, and TNF-α). Right ventricular hypertrophy was calculated using Fulton’s index (weight of the right ventricle divided by the combined weight of the left ventricle and the intraventricular septum). Lung sections were stained with Movat Pentachrome and examined for the presence of immune cells and medial wall thickening of pulmonary arteries. In a separate group of animals, bronchoalveolar lavage fluid (BALF) and blood obtained by cardiac puncture were cytocentrifuged and stained with hematoxylin &amp; eosin for immune cell counts. Results: Undernourished rats had a lower body weight than normally nourished rats at postnatal day 21 (n=11-17; p&lt;0.0001). Undernourished animals had an increased number of immune cells in BALF and lung tissue and an elevated neutrophil count in the blood which were all decreased with concurrent L-citrulline treatment (n=3-4; p&lt;0.001). L-citrulline treatment also prevented the increased mRNA expression of pro-inflammatory mediators in the lungs [MCP-1/CCL2, TNF-α, and IL-1β] (n=8; p&lt;0.05) and pancreas [MCP-1/CCL2, MIP-1α /CCL3, IL-6, and TNF-α] (n=3; p&lt;0.05) of undernourished animals. These animals had a greater pulmonary artery medial wall area and Fulton’s index when compared to normally nourished animals treated with saline or L-citrulline (n=3-4; p&lt;0.001). Concurrent L-citrulline treatment in undernourished animals prevented pulmonary artery vascular remodeling and heart tissue histopathology such that the medial wall area and Fulton’s index did not differ from that of animals in control groups (n=4; p&lt;0.01). Conclusion: L-citrulline effectively mitigates the adverse effects of postnatal undernutrition, reducing lung, pancreatic, and systemic inflammation and histopathology in the lung and heart associated with PH. As a safe, well-tolerated, and inexpensive treatment, L-citrulline presents promising therapeutic potential that could prevent short and long-term morbidities associated with growth restriction and undernutrition in preterm infants. This work was funded by the Women's Auxiliary of The Hospital for Sick Children. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association of Fetal Catecholamines With Neonatal Hypoglycemia

Perinatal stress and fetal growth restriction increase the risk of neonatal hypoglycemia. The underlying pathomechanism is poorly understood. In a sheep model, elevated catecholamine concentrations were found to suppress intrauterine insulin secretion, followed by hyperresponsive insulin secretion once the adrenergic stimulus subsided. To determine whether neonates with risk factors for hypoglycemia have higher catecholamine concentrations in umbilical cord blood (UCB) and/or amniotic fluid (AF) and whether catecholamines are correlated with postnatal glycemia. In a prospective cohort study of 328 neonates at a tertiary perinatal center from September 2020 through May 2022 in which AF and UCB were collected immediately during and after delivery, catecholamines and metanephrines were analyzed using liquid chromatography with tandem mass spectrometry. Participants received postnatal blood glucose (BG) screenings. Risk factor for neonatal hypoglycemia. Comparison of catecholamine and metanephrine concentrations between at-risk neonates and control participants, and correlation of concentrations of catecholamines and metanephrines with the number and severity of postnatal hypoglycemic episodes. In this study of 328 neonates (234 in the risk group: median [IQR] gestational age, 270 [261-277] days; and 94 in the control group: median [IQR] gestational age, 273 [270-278] days), growth-restricted neonates showed increased UCB median (IQR) concentrations of norepinephrine (21.10 [9.15-42.33] vs 10.88 [5.78-18.03] nmol/L; P < .001), metanephrine (0.37 [0.13-1.36] vs 0.12 [0.08-0.28] nmol/L; P < .001), and 3-methoxytyramine (0.149 [0.098-0.208] vs 0.091 [0.063-0.149] nmol/L; P = .001). Neonates with perinatal stress had increased UCB median (IQR) concentrations of norepinephrine (22.55 [8.99-131.66] vs 10.88 [5.78-18.03] nmol/L; P = .001), normetanephrine (1.75 [1.16-4.93] vs 1.25 [0.86-2.56] nmol/L; P = .004), and 3-methoxytyramine (0.120 [0.085-0.228] vs 0.091 [0.063-0.149] nmol/L; P = .008) (P < .0083 was considered statistically significant). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were negatively correlated with AF C-peptide concentration (rs = -0.212, P = .005; rs = -0.182, P = .016; and rs = -0.183, P = .016, respectively [P < .017 was considered statistically significant]). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were positively correlated with the number of hypoglycemic episodes (BG concentration of 30-45 mg/dL) (rs = 0.146, P = .01; rs = 0.151, P = .009; and rs = 0.180, P = .002, respectively). Concentrations of UCB metanephrine and 3-methoxytyramine were negatively correlated with the lowest measured BG concentration (rs = -0.149, P = .01; and rs = -0.153, P = .008, respectively). Neonates at risk for hypoglycemia displayed increased catecholamine and metanephrine concentrations that were correlated with postnatal hypoglycemic episodes and lower BG levels; these results are consistent with findings in a sheep model that fetal catecholamines are associated with neonatal β-cell physiology and that perinatal stress or growth restriction is associated with subsequent neonatal hyperinsulinemic hypoglycemia. Improving the pathomechanistic understanding of neonatal hypoglycemia may help to guide management of newborns at risk for hypoglycemia.

Neurodevelopmental outcomes of preterm and growth-restricted neonate with congenital heart defect: a systematic review and meta-analysis.

Based on a low level of evidence, prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. Further evidence is needed to confirm these findings. PROSPERO [CRD42020201414]. • Children born with CHD, preterm birth, or growth restriction at birth are independently at higher risk for neurodevelopmental impairment. • The additional effect of preterm birth and/or growth restriction on neurodevelopmental outcomes in children with CHD remains unclear. • Prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. • Children with CHD, particularly those born preterm or with growth restriction, should undergo lifelong systematic comprehensive neurodevelopmental assessment.

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.

Time to Attain Full Enteral Feeds Among Preterm Fetal Growth Restricted Neonates With Absent/Reversed End-Diastolic Flow

Time to Attain Full Enteral Feeds Among Preterm Fetal Growth Restricted Neonates With Absent/Reversed End-Diastolic Flow

Subclinical myocardial dysfunction among fetal growth restriction neonates: a case-control study

Objectives To evaluate cardiac structural and functional changes in neonates with fetal growth restriction (FGR) compared to appropriate-for-gestational-age (AGA) neonates using conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography. Method This case-control study included 85 FGR neonates and 75 non-FGR, weight adequate for gestational age neonates. Among these, 37 were symmetric FGR and 48 were asymmetric FGR. All the biophysical profiles of these newborns were assessed. An echocardiographic test was performed to evaluate cardiac dimension, Left ventricular ejection fraction (LV EF), Mitral valve Doppler flow velocities, myocardial performance index, tissue annular velocities, and LV global longitudinal strain (GLS). Results Although LVEF was found to be within the normal range, mean EF was reduced among neonates with FGR than non-FGR controls (EF: 66.14 ± 3.85% vs 69.46 ± 3.58%; p < 0.001, in FGR and non-FGR, respectively). Furthermore, LV E/E’ a measure of LV diastolic function was altered among both types of FGR neonates. Similarly, LV GLS was reduced among FGR neonates (LV GLS: −20.69 ± 2.7% vs −19.06 ± 2.9%; p < 0.001 in non-FGR and FGR, respectively). Conclusion FGR neonates exhibit significant alterations in cardiac geometry compared to AGA controls. FGR neonates also demonstrated a significant reduction in LV EF, FS, and LV global longitudinal strain, depicting failure to adapt to the increased cardiac workload after birth.

Cardiovascular decline in offspring during the perinatal period in an ovine model of fetal growth restriction.

Fetal growth restriction (FGR) increases the risk cardiovascular disease (CVD) in adulthood. Placental insufficiency and subsequent chronic fetal hypoxemia are causal factors for FGR, leading to a redistribution of blood flow that prioritizes vital organs. Subclinical signs of cardiovascular dysfunction are evident in growth-restricted neonates; however, the mechanisms programming for CVD in adulthood remain unknown. This study aimed to determine the potential mechanisms underlying structural and functional changes within the heart and essential (carotid) and nonessential (femoral) vascular beds in growth-restricted lambs. Placental insufficiency was surgically induced in ewes at 89 days gestational age (dGA, term = 148dGA). Three age groups were investigated: fetal (126dGA), newborn (24 h after preterm birth), and 4-wk-old lambs. In vivo and histological assessments of cardiovascular indices were undertaken. Resistance femoral artery function was assessed via in vitro wire myography and blockade of key vasoactive pathways including nitric oxide, prostanoids, and endothelium-dependent hyperpolarization. All lambs were normotensive throughout the first 4 wk of life. Overall, the FGR cohort had more globular hearts compared with controls (P = 0.0374). A progressive decline in endothelium-dependent vasodilation was demonstrated in FGR lambs compared with controls. Further investigation revealed that impairment of the prostanoid pathway may drive this reduction in vasodilatory capacity. Clinical indicators of CVD were not observed in our FGR lambs. However, subclinical signs of cardiovascular dysfunction were present in our FGR offspring. This study provides insight into potential mechanisms, such as the prostanoid pathway, that may warrant therapeutic interventions to improve cardiovascular development in growth-restricted newborns.NEW & NOTEWORTHY Our findings provide novel insight into the potential mechanisms that program for cardiovascular dysfunction in growth-restricted neonates as our growth-restricted lambs exhibited a progressive decline in endothelium-dependent vasodilation in the femoral artery between birth and 4 wk of age. Subsequent analyses indicated that this reduction in vasodilatory capacity is likely to be mediated by the prostanoid pathway and prostanoids could be a potential target for therapeutic interventions for fetal growth restriction (FGR).

Cardiovascular responses to mild perinatal asphyxia in growth-restricted preterm lambs.

Growth-restricted neonates have worse outcomes after perinatal asphyxia, with more severe metabolic acidosis than appropriately grown neonates. The cardiovascular physiology associated with fetal growth restriction (FGR) may alter their response to asphyxia. However, research on asphyxia in FGR is limited. Here we compared cardiovascular hemodynamics in preterm FGR and control lambs during mild perinatal asphyxia. We induced FGR in one twin at 89 days gestation (term 148 days), while the other served as a control. At 126 days gestation, lambs were instrumented to allow arterial blood pressure and regional blood flow recording, and then mild perinatal asphyxia was induced by umbilical cord clamping, and resuscitation followed neonatal guidelines. FGR lambs maintained carotid blood flow (CBF) for 7 min, while control lambs rapidly decreased CBF (P < 0.05). Fewer growth-restricted lambs needed chest compressions for return of spontaneous circulation (ROSC) (17 vs. 83%, P = 0.02). The extent of blood pressure overshoot after ROSC was similar, but it took longer for MAP to return to baseline in FGR lambs (18.83 ± 0.00 vs. 47.67 ± 0.00 min, P = 0.003). Growth-restricted lambs had higher CBF after ROSC (P < 0.05) and displayed CBF overshoot, unlike control lambs (P < 0.03). In conclusion, preterm growth-restricted lambs show resilience during perinatal asphyxia based on prolonged CBF maintenance and reduced need for chest compressions during resuscitation. However, CBF overshoot after ROSC may increase the risk of cerebrovascular injury in FGR.NEW & NOTEWORTHY Preterm growth-restricted lambs maintain carotid blood flow for longer than control lambs during asphyxia and have a lower requirement for chest compressions than control lambs during resuscitation. Preterm growth-restricted, but not control, lambs displayed an overshoot in carotid blood flow following return of spontaneous circulation.

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.

Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction

BackgroundFetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. AimEchocardiographic assessment of heart function in FGR neonates first three days after birth. Study designProspective observational study. SubjectsFGR- and non-FGR neonates. Outcome measuresM-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e′ of the atrioventricular plane day one, two and three after birth. ResultsCompared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e′ (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e′ (15 (7) %, p = 0.049), right a′ (18 (6) %, p = 0.001), left E/e′ (25 (10) %, p = 0.015) and right E/e′ (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. ConclusionsFGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.

Association between gestational blood lipids and TSH levels and pregnancy outcome of patients with subclinical hypothyroidism.

To investigate the association between gestational blood lipids and thyroid stimulating hormone (TSH) levels and pregnancy outcomes of patients with subclinical hypothyroidism (SCH). In this retrospective observational study, we analyzed the clinical data of 82 patients (case group) with gestational SCH treated in our hospital from January 2021 to January 2022 at gestational weeks 25-33 and grouped them according to whether SCH was well controlled by treatment (case Group-A: well controlled, n=55; case Group-B: poorly controlled, n=27), and the clinical data of 41 pregnant women (control group) undergoing physical examination during the same period. After comparing the blood lipids and TSH levels of the three groups, we compared their adverse pregnancy outcomes to assess the possible correlations between blood lipids and TSH levels and pregnancy outcomes. The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and TSH in the case Group-B were significantly higher than those in the case Group-A and the control group (P<0.05). Compared with case Group-B and the control group, the incidence of premature delivery, abortion and neonatal growth restriction was higher in case Group-A (P<0.05). Among 82 patients in the case group 42 presented adverse pregnancy outcomes. The levels of TC, TG, LDL-C and TSH in mothers and infants in the adverse outcome group were significantly higher than those in the favorable outcome group (P<0.05). Our Pearson analysis results showed that the levels of TC, TG and LDL-C were positively correlated with the TSH levels and the pregnancy outcomes, and that TSH was positively correlated with pregnancy outcomes (P<0.05). The levels of TC, TG, LDL-C and TSH in patients with poorly controlled SCH were increased during pregnancy, and were associated with the pregnancy outcomes and positively correlated with each other.

Performance of the INTERGROWTH-21st and World Health Organization fetal growth charts for the detection of small-for-gestational age neonates in Latin America.

To evaluate the performance of INTERGROWTH-21st (IG-21st ) and World Health Organization (WHO) fetal growth charts to identify small-for-gestational-age (SGA) and fetal growth restriction (FGR) neonates, as well as their specific risks for adverse neonatal outcomes. Multicenter cross-sectional study including 67 968 live births from 10 maternity units across four Latin American countries. According to each standard, neonates were classified as SGA and FGR (birth weight <10th and less than third centiles, respectively). The relative risk (RR) and diagnostic performance for a low APGAR score and low ponderal index were calculated for each standard. WHO charts identified more neonates as SGA than IG-21st (13.9% vs 7%, respectively). Neonates classified as having FGR by both standards had the highest RR for a low APGAR (RR, 5.57 [95% confidence interval (CI), 3.99-7.78]), followed by those who were SGA by both curves (RR, 3.27 [95% CI, 2.52-4.24]), while neonates with SGA identified by WHO alone did not have an additional risk (RR, 0.87 [95% CI, 0.55-1.39]). Furthermore, the diagnostic odds ratio for a low APGAR was higher when IG-21st was used. In a population from Latin America, the WHO charts seem to identify more SGA neonates, but the diagnostic performance of the IG-21st charts for low APGAR score and low ponderal index is better.