Search

Genes associated with specific neurocognitive phenotypes in Williams–Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams–Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams–Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient retained these genes but showed neurodevelopmental abnormalities. By comparing the genotypes and phenotypes of patients with typical and atypical deletions and previous reports in the literature, we hypothesize that the BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS. [ABSTRACT FROM AUTHOR]

We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort [87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls], with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD). [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety profile of phosphodiesterase-5 inhibitors (PDE-5i) in pregnancy are unclear from the few relatively small diverse studies that have used them.Objective: To assess the safety profile and clinical outcomes of PDE-5i use in pregnancy.Search Strategy: We searched Embase, PubMed, CENTRAL, Prospero and Google Scholar to identify randomised controlled trials (RCTs) reporting the use of any PDE-5i in pregnancy up to September 2021.Selection Criteria: RCTs reporting obstetric or perinatal outcomes or maternal adverse outcomes in women taking PDE5i in pregnancy.Data Collection and Analysis: Risk ratios (RR), 95% confidence intervals (95% CI) and 95% prediction intervals were calculated and pooled for analysis.Results: We identified 1324 citations, of which 10 studies including 1090 participants met the inclusion criteria. Only tadalafil and sildenafil were reported as used in pregnancy. Two studies using tadalafil and eight sildenafil. Nine of ten studies were assessed at having of low risk of bias. PDE-5i use was associated with an increased risk of headaches (RR 1.41, 95% CI 0.97-2.05), flushing (RR 2.59, 95% CI 0.69-9.90) and nasal bleeding (RR 10.53, 95% CI 1.36-81.3); an increase in vaginal birth when used for non-fetal growth restriction (FGR) indications (RR 1.24, 95% CI 1.00-1.55) and a reduction in risk of operative birth for intrapartum fetal compromise (RR 0.58, 95% CI 0.38-0.88). There was no evidence of any increase in risk of perinatal death (RR 0.89, 95% CI 0.56-1.43). However, use for the treatment of FGR increased the risk of persistent pulmonary hypertension of the newborn (PPHN) (RR 2.52, 95% CI 1.00-6.32).Conclusions: This meta-analysis suggests PDE-5i use in pregnancy is associated with mild maternal side effects and lower risk of operative birth for intrapartum fetal distress. Prolonged use for the treatment of FGR may increase the risk of PPHN.Tweetable Abstract: PDE-5i use in pregnancy is associated with mild maternal side effects, lower operative birth for intrapartum fetal distress and a possible increase in persistent pulmonary hypertension of the newborn when used for the treatment of fetal growth restriction. [ABSTRACT FROM AUTHOR]

The effect of dilute solute additions on growth restriction in Cu-, Al-, Mg- and Ti-based binary and ternary alloys was assessed by means of the heuristic growth restriction parameter (β) modelling framework. The CALPHAD (calculation of phase diagrams) methodology was used to calculate β values from the m and k values, at first approximation, as well as from the liquid-to-solid fraction to obtain true β values. Grain size values from the literature were plotted against the corresponding true β values, showing a negative or inverse correlation between the two. [ABSTRACT FROM AUTHOR]

Animals are often not growing at the maximum rate, but can compensate for a bad start of life by subsequently increasing growth rate. While this compensatory growth is widespread, its direct fitness consequences are seldom investigated and its genetic basis is unknown.We investigated the genetic regulation, as well as fitness and lifespan consequences of compensatory growth in response to temperature, using Caenorhabditis elegans knockout of the thermo‐sensitive TRP ion channel TRPA‐1, involved in temperature recognition. We exposed juvenile worms to cold, favourable (intermediate) or warm temperatures in order to delay or speed up development.Wild‐type worms initially exposed to cold temperature experienced slower growth but after being switched to a more favourable temperature, they expressed compensatory growth and caught up in size. Those initially reared at warmer temperatures than favourable experienced slower growth and attained smaller adult size after being switched to the most favourable temperature.Compensatory growth also altered the reproductive schedule. While rate‐sensitive individual fitness decreased by cold juvenile temperatures, as a direct effect of the substantial developmental delay, once worms returned to more favourable temperature, they shifted their reproductive schedule towards early reproduction. Therefore, when focusing on the post‐treatment period, the reproductive rate increased even though lifetime reproductive success was unaffected. Surprisingly, compensatory growth did not reduce adult lifespan. In contrast to the findings for wild‐type worms, juvenile temperature did not induce compensatory or slowed‐down growth in the trpa‐1 knockout mutants.We thus show that the trpa‐1 is involved in the network regulating temperature‐induced compensatory growth in C. elegans and that this compensatory growth can influence the reproductive rate. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Grain refinement is of importance for metallic materials since it provides multiple benefits, such as improved castability, reduced casting defects and improved mechanical properties. From extensive research carried out in the past decades, it has been widely accepted that solute is one of the crucial factors for achieving grain refinement. However, grain refinement is a complex phenomenon, depending on not only solutes in the melt to provide growth restriction but also the physical and chemical nature of the nucleant particles (either endogenous or exogenous). Although significant progress has been made on the subject, some critical questions still remain open, and a comprehensive understanding of the mechanisms of solute effect on grain refinement is still desirable. In this paper, we present an overview of the solute effect on grain refinement based on our recent advances made in the LiME Research Hub. This covers the effect of solute on nucleation potency of nucleant particles due to interfacial segregation, columnar to equiaxed transition (CET), growth restriction and eventually on the overall grain refinement. [ABSTRACT FROM AUTHOR]

Preterm birth increases the risk of cardiometabolic disease in adulthood. Infants born during the second trimester of pregnancy, a critical period of hypothalamic development, are at risk of sodium (Na) depletion due to renal immaturity and large urine Na losses. We previously demonstrated in male mice that Na restriction during the equivalent mouse hypothalamic development period (PD21-PD42) programs long-term changes in energy balance via increased thermogenic sympathetic nervous activity. We therefore hypothesized that early-life Na restriction programs changes in cardiovascular control via altered autonomic activity. C57BL/6J male mice were supplied a low (0.04%) Na or supplemented (0.30%) Na diet from PD21-PD42, before return to standard (0.15%) Na diet. Hemodynamic and autonomic functions were assessed by radiotelemetry and acute administration of autonomic antagonists before and after all animals were switched to a high Na diet (HSD; 1% Na) at 12 weeks of age. Mice were additionally treated with the angiotensin II type 1 receptor (AT 1 R) antagonist, losartan, for two weeks. On standard diet, early-life Na restriction resulted in small but significantly different hemodynamic responses to autonomic blockers without effect on systolic blood pressure (SBP) or heart rate (HR). HSD increased SBP in 0.04% but not 0.30% Na mice, accompanied by increased cardiac sympathetic activity. Losartan had a greater BP lowering effect in early life Na-restricted mice. Our findings suggest Na restriction during a critical hypothalamic developmental period programs long-term changes in autonomic control of cardiovascular functions and may offer insight into the increased risk of cardiovascular disease in former preterm infants.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impacts intrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm 3 /kg, 95% CI:(2.5;13.7 cm 3 /kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Undernutrition-induced growth restriction in the early stages of life increases the risk of chronic disease in adulthood. Although metabolic impairments have been observed, few studies have characterized the gut microbiome and gut-liver metabolome pro- files of growth-restricted animals during early-to-mid-life development. To induce growth restriction, mouse offspring were either born to gestational undernutrition (GUN) or suckled from postnatal undernutrition (PUN) dams fed a protein-restricted diet (8% protein) or control diet (CON; 20% protein) until weaning at postnatal age of 21 days (PN21). At PN21, all mice were fed the CON diet until adulthood (PN80). Livers were collected at PN21 and PN80, and fecal samples were collected weekly starting at PN21 (postweaning week 1) until PN80 (postweaning week 5) for gut microbiome and metabolome analyses. PUN mice exhibited the most alterations in gut microbiome and gut and liver metabolome compared with CON mice. These mice had altered fecal microbial β-diversity (P = 0.001) and exhibited higher proportions of Bifidobacteriales [linear mixed model (LMM) P = 7.1 x 10-6), Clostridiales (P = 1.459 x 10-5), Erysipelotrichales (P = 0.0003), and lower Bacteroidales (P = 4.1 x 10-5)]. PUN liver and fecal metabolome had a reduced total bile acid pool (P < 0.01), as well as lower abundance of riboflavin (P = 0.003), amino acids [i.e., methionine (P = 0.0018), phenylalanine (P = 0.0015), and tyrosine (P = 0.0041)], and higher excreted total peptides (LMM P = 0.0064) compared with CON. Overall, protein restriction during lactation permanently alters the gut microbiome into adulthood. Although the liver bile acids, amino acids, and acyl-carnitines recovered, the fecal peptides and microbiome remained permanently altered into adulthood, indicating that inadequate protein intake in a specific time frame in early life can have an irreversible impact on the microbiome and fecal metabolome. [ABSTRACT FROM AUTHOR]

The effect of ultrasonic melt treatment (UST) on the solidification microstructure of an Al–5Ti–1B alloy containing high-volume fractions of Al3Ti and TiB2 particles is investigated for various UST times with different melt holding times. The as-cast Al–5Ti–1B alloy is composed of TiB2 and polygonal Al3Ti particles (present prior to UST), plate-like Al3Ti particles, and Al grains (formed during UST and/or solidification). The UST causes a size reduction and homogeneous distribution of the TiB2-agglomerated region containing many submicron-sized TiB2 particles pushed to the grain boundaries. The UST slightly decreases the size and improves the distribution of polygonal Al3Ti particles enriched in the TiB2-agglomerated region. Unlike the TiB2 and polygonal Al3Ti particles, which exhibit a minor refining effect, the plate-like Al3Ti particles show a significant refinement with UST application. The UST has a significant effect on the size distribution of Al grains by inducing the formation of medium-sized grains at the expense of small and large grains; however, it only has a slight effect on grain refinement. The degree of microstructure modification increases with increasing UST time but decreases with melt holding time after UST. The mechanisms for the refinement and dispersion of the TiB2 and Al3Ti particles and Al grains are discussed considering fragmentation, nucleation, and growth behaviors induced by the UST and subsequent solidification. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the effect of impedance cardiography directed medical antihypertensive therapy on fetal growth restriction and perinatal mortality in women with chronic hypertension.Study Design: A retrospective study was conducted on 958 women referred to the Maternal Hypertension Center at Cabell Huntington Hospital between 2005 and 2014 for the indication of chronic hypertension.Main Outcome Measures: Serial assessments of maternal hemodynamics were obtained using non-invasive impedance cardiography. Vasodilators were initiated for increased systemic vascular resistance. Elevated cardiac output was treated with beta blockade.Results: Blood pressure at initial visit was used to stratify patients into five groups. Initial blood pressure of <130 systolic or <80 diastolic had 24 cases of growth restriction (6.8%) and 6 perinatal deaths (1.7%), 130-139 systolic or 80-89 diastolic resulted in 29 cases of growth restriction (9.3%) and 9 perinatal deaths (2.9%), 140-149 systolic or 90-99 diastolic 14 cases of growth restriction (6.5%) and 3 perinatal deaths (1.4%), 150-159 systolic or 100-109 diastolic had 5 cases of growth restriction (8.6%) and 4 perinatal deaths (6.89%), and >160 systolic or >110 diastolic 3 cases of growth restriction (13%) with no perinatal deaths. There were no differences in growth restriction (p = .59) or perinatal death (p = .15) between the groups.Conclusion: The rates of IUGR and perinatal mortality did not increase even with increasing severity of maternal hypertension. This low cost and non-invasive test should be considered for optimizing rates of growth restriction and perinatal mortality in pregnancies complicated by chronic hypertension. [ABSTRACT FROM AUTHOR]

BACKGROUND: Approximately 8-23% of premature infants develop pulmonary hypertension (PH), and this diagnosis confers a higher possibility of mortality. As a result, professional societies recommend PH screening in premature infants. However, the risk factors for and the outcomes of PH may differ depending on the timing of its diagnosis, and little evidence is available to determine at-risk infants in the referral neonatal population. The objective of this study was to define clinical and echocardiographic characteristics of infants with pulmonary hypertension during the neonatal hospital course and at or near-term. METHODS: Infants who had the following billing codes: < 32 weeks, birth weight

IntroductionThe incidence of preeclampsia (PE) is about 2–8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost.Methods and AnalysisThis is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE.Ethics and DisseminationThe study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020).Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04767438.

In this study, the potential toxicity of isoprocarb was demonstrated using zebrafish embryos. We treated isoprocarb (0, 29, and 58 mg/L) to the zebrafish embryos for 72 h then, we estimated morphological changes and apoptotic cell numbers. The increasing extent of apoptosis from the anterior to posterior region of developing zebrafish larvae was correlated with toxicity in the overall development process, including growth and normal organ formation. The appearance of abnormalities in the isoprocarb-treated groups in comparison to normal developing zebrafish larvae was verified using quantitative image analysis based on ImageJ software program. The vascular system comprising a complex interconnection of blood vessels was visualized in vessel-fluorescent transgenic zebrafish (fli1:eGFP). The main vasculature was malformed on isoprocarb treatment, and this was also related to cardiac defects. Taken together, normal embryonic development in zebrafish was interrupted owing to the acute toxicity of isoprocarb.

Computational hemodynamic simulations are becoming increasingly important for cardiovascular research and clinical practice, yet incorporating numerical simulations of human fetal circulation is relatively underutilized and underdeveloped. The fetus possesses unique vascular shunts to appropriately distribute oxygen and nutrients acquired from the placenta, adding complexity and adaptability to blood flow patterns within the fetal vascular network. Perturbations to fetal circulation compromise fetal growth and trigger the abnormal cardiovascular remodeling that underlies congenital heart defects. Computational modeling can be used to elucidate complex blood flow patterns in the fetal circulatory system for normal versus abnormal development. We present an overview of fetal cardiovascular physiology and its evolution from being investigated with invasive experiments and primitive imaging techniques to advanced imaging (4D MRI and ultrasound) and computational modeling. We introduce the theoretical backgrounds of both lumped-parameter networks and three-dimensional computational fluid dynamic simulations of the cardiovascular system. We subsequently summarize existing modeling studies of human fetal circulation along with their limitations and challenges. Finally, we highlight opportunities for improved fetal circulation models.

Numerous studies have focused on the molecular signaling pathways that govern the development and growth of lymphatics in the hopes of elucidating promising druggable targets. G protein-coupled receptors (GPCRs) are currently the largest family of membrane receptors targeted by FDA-approved drugs, but there remain many unexplored receptors, including orphan GPCRs with no known biological ligand or physiological function. Thus, we sought to illuminate the cadre of GPCRs expressed at high levels in lymphatic endothelial cells and identified four orphan receptors: GPRC5B, AGDRF5/GPR116, FZD8 and GPR61. Compared to blood endothelial cells, GPRC5B is the most abundant GPCR expressed in cultured human lymphatic endothelial cells (LECs), and in situ RNAscope shows high mRNA levels in lymphatics of mice. Using genetic engineering approaches in both zebrafish and mice, we characterized the function of GPRC5B in lymphatic development. Morphant gprc5b zebrafish exhibited failure of thoracic duct formation, and Gprc5b−/− mice suffered from embryonic hydrops fetalis and hemorrhage associated with subcutaneous edema and blood-filled lymphatic vessels. Compared to Gprc5+/+ littermate controls, Gprc5b−/− embryos exhibited attenuated developmental lymphangiogenesis. During the postnatal period, ~30% of Gprc5b−/− mice were growth-restricted or died prior to weaning, with associated attenuation of postnatal cardiac lymphatic growth. In cultured human primary LECs, expression of GPRC5B is required to maintain cell proliferation and viability. Collectively, we identify a novel role for the lymphatic-enriched orphan GPRC5B receptor in lymphangiogenesis of fish, mice and human cells. Elucidating the roles of orphan GPCRs in lymphatics provides new avenues for discovery of druggable targets to treat lymphatic-related conditions such as lymphedema and cancer. [ABSTRACT FROM AUTHOR]

Background: Wolf-Hirschhorn syndrome (WHS) is a well-defined disorder, whose core phenotype encompasses growth restriction, facial gestalt, intellectual disability and seizures. Nevertheless, great phenotypic variability exists due to the variable extent of the responsible 4p deletion. In addition, exome sequencing analyses, recently identified two genes, namely NSD2 and NELFA, whose loss-of-function variants contribute to a clinical spectrum consistent with atypical or partial WHS. The observation of patients exhibiting clinical features resembling WHS, with only mild developmental delay and without the typical dysmorphic features, carrying microdeletions sparing NSD2, has lead to the hypothesis that NSD2 is responsible for the intellectual disability and the facial gestalt of WHS. While presenting some of the typical findings of WHS (intellectual disability, facial gestalt, microcephaly, growth restriction and congenital heart defects), NSD2-deleted children tend to display a milder spectrum of skeletal abnormalities, usually consisting of clinodactyly, and do not exhibit seizures. We describe the clinical picture of a child with WHS due to a de novo mutation of NSD2 and discuss the clinical and diagnostic implications. Case presentation: A 6-year-old boy was evaluated for a history of intrauterine growth restriction, low birth weight, neonatal hypotonia, and psychomotor delay. No episodes of seizure were reported. At physical examination, he displayed marphanoid habitus, muscle hypotrophy and facial dysmorphisms consisting in high frontal hairline, upslanting palpebral fissures and full lips with bifid ugula. Cryptorchidism, shawl scrotum, mild clinodactyly of the right little finger and bilateral syndactyly of the II and III toes with sandal gap were also noted. The radiographic essay demonstrated delayed bone age and echocardiography showed mild mitral prolapse. Whole genome sequencing analysis revealed a heterozygous de novo variant of NSD2 (c.2523delG). Conclusions: Full WHS phenotype likely arises from the cumulative effect of the combined haploinsufficiency of several causative genes mapping within the 4p16.3 region, as a contiguous genes syndrome, with slightly different phenotypes depending on the specific genes involved in the deletion. When evaluating children with pictures resembling WHS, in absence of seizures, clinicians should consider this differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Introduction: There is clear evidence that fetuses with intrauterine growth restriction (IUGR) do not receive the minimum evidence-based care during their antenatal management. Objective: Considering that optimal management of IUGR may reduce neonatal morbi-mortality in IUGR, the objective of the present study was to evaluate the impact of antenatal management of IUGR according to the recommendations of the French college of gynecologists and obstetricians (CNGOF) on the neonatal prognosis of IUGR fetuses. Study design: From a historical cohort of 31,052 children, born at the Femme Mère Enfant hospital (Lyon, France) between January 1, 2011 and December 31, 2017, we selected the population of IUGR fetuses. The minimum evidence-based care (MEC) in the antenatal management of fetuses with IUGR was defined according to the CNGOF recommendations and neonatal prognosis of early and late IUGR fetuses were assessed based on the whether or not they received MEC. The neonatal prognosis was defined according to a composite criterion that included neonatal morbidity and mortality. Results: A total of 1020 fetuses with IUGR were studied. The application of MEC showed an improvement in the neonatal prognosis of early-onset IUGR (p = 0.003), and an improvement in the neonatal prognosis of IUGR born before 32 weeks (p = 0.030). Multivariate analysis confirmed the results showing an increase in neonatal morbi-mortality in early-onset IUGR in the absence of MEC with OR 1.79 (95% CI 1.01–3.19). Conclusion: Diagnosed IUGR with MEC had a better neonatal prognosis when born before 32 weeks. Regardless of the birth term, MEC improved the neonatal prognosis of fetuses with early IUGR. Improvement in the rate of MEC during antenatal management has a significant impact on neonatal prognosis. [ABSTRACT FROM AUTHOR]

Objective: To understand the relationship between birth weight and altitude to improve health outcomes in high-altitude populations, to systematically assess the impact of altitude on the likelihood of low birth weight (LBW), small for gestational age (SGA), and spontaneous preterm birth (sPTB), and to estimate the magnitude of reduced birth weight associated with altitude. Methods: PubMed, OvidEMBASE, Cochrane Library, Medline, Web of Science, and clinicaltrials.gov were searched (from inception to November 11, 2020). Observational, cohort, or case-control studies were included if they reported a high altitude (>2500 m) and appropriate control population. Results: Of 2524 studies identified, 59 were included (n = 1 604 770 pregnancies). Data were abstracted according to PRISMA guidelines, and were pooled using random-effects models. There are greater odds of LBW (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.33-1.62, P < 0.001), SGA (OR 1.88, 95% CI 1.08-3.28, P = 0.026), and sPTB (OR 1.23, 95% CI 1.04-1.47, P = 0.016) in high-versus low-altitude pregnancies. Birth weight decreases by 54.7 g (±13.0 g, P < 0.0001) per 1000 m increase in altitude. Average gestational age at delivery was not significantly different. Conclusion: Globally, the likelihood of adverse perinatal outcomes, including LBW, SGA, and sPTB, increases in high-altitude pregnancies. There is an inverse relationship between birth weight and altitude. These findings have important implications for the increasing global population living at altitudes above 2500 m. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the umbilical vein and uterine arteries blood flow volume (UV-Q, UtA-Q) in late-term pregnancies.Study Design: This was a prospective observational cohort study of singleton pregnancies ≥40 + 0 weeks in which UV-Q and UtA-Q, both absolute and normalized for estimated fetal weight (EFW) values, were evaluated in relation to AC drop of ≥20 percentiles from 20 weeks to term, Doppler signs of fetal cerebral blood flow redistribution and composite adverse perinatal outcome. The presence of neonatal hypoglycaemia and the need of formula milk supplementation were also examined.Results: The study population comprised 200 women. Fetuses with AC drop (n = 34) had a significantly lower UV-Q and UV-Q/EFW than fetuses without AC drop (n = 166): median UV-Q 184 ml/min (IQR 143-225) vs 233 ml/min (IQR 181-277), p = 0.0006; median UV-Q/EFW 55 ml/min/kg (IQR 42-66) vs 63 ml/min/kg (IQR 48-74), p = 0.03. Fetuses with cerebral blood flow redistribution (n = 48) had a significantly lower UV-Q and UV-Q/EFW than those without (n = 134): median UV-Q 210 ml/min (IQR 155-263) vs 236 ml/min (IQR 184-278), p = 0.04; median UV-Q/EFV 58 ml/min/kg (IQR 45-70) vs 65 ml/min/kg (IQR 50-76), p = 0.04. There was a significant moderate correlation between middle cerebral artery pulsatility index (MCA-PI) and UV-Q and UV-Q/EFW (Spearman Rho -0.20 and -0.20; p = 0.008 and p = 0.006).Conclusions: The umbilical vein blood flow volume might have a potential role to identify fetuses with stunted growth in late-term pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: Fetoplacental Doppler is considered to be a key tool for the diagnosis of placenta-mediated fetal growth restriction(FGR). We aimed to determine the diagnostic accuracy of fetoplacental Doppler for specific placental diseases.Methods: A retrospective cohort study of all women with a singleton pregnancy and an antenatal diagnosis of SGA fetus(estimated fetal weight <10th centile for gestational age), who underwent fetoplacental Doppler assessment within 2 weeks before birth. Primary exposure was any abnormal Doppler result, defined as an abnormal umbilical artery(UA) Doppler, middle cerebral artery(MCA) Doppler, cerebroplacental-ratio(CPR), or umbilico-cerebral ratio(UCR). Study outcomes were abnormal placental pathology: maternal vascular malperfusion(MVM), villitis of unknown etiology(VUE), or fetal vascular malperfusion(FVM).Results: A total of 558 women with a singleton SGA fetus were included, of whom 239(42.8%) had an abnormal fetoplacental Doppler findings. UA Doppler had the lowest detection rate for abnormal placental pathology. MCA Doppler exhibited a significantly higher detection rate for all types of pathology. CPR and UCR exhibited highest detection rates for all types of placental pathology, however, were also associated with the highest false positive rate. The combination of fetoplacental Doppler with the severity of SGA and maternal hypertensive status achieved a high negative predictive value MVM lesions(97%). In contrast, fetoplacental Doppler did not improve the negative predictive value for non-MVM pathology(VUE or FVM).Discussion: Among SGA fetuses, the combination of UA and MCA Doppler is highly accurate in ruling out FGR due to MVM placental pathology, but is of limited value in excluding FGR due to underlying non-MVM pathologies. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to determine additional variables, next to umbilical artery (UA) Doppler, to help differentiate between Type II and III selective fetal growth restriction (sFGR).Methods: Retrospective analysis categorizing monochorionic diamniotic twin pregnancies with sFGR and abnormal UA Doppler as either Type II or III sFGR based on the diameter of the artery-to-artery (AA) anastomosis of ≤2 or >2 mm, respectively on placental examination after birth. This exploratory study compared maternal characteristics, pregnancy outcome, placental characteristics, and ultrasound features between the two groups.Results: We included 40 sFGR placentas, 13 were classified as Type II and 27 as Type III. Maternal age was higher in Type II. Small Type II twins had lower birth weights (BWs) for gestational age and BW discordance was higher in Type II. Type III placentas were more unevenly divided, but Type III pairs differed less in BW than expected relative to their placental discordance. Type III placentas more commonly had a vein-to-vein anastomosis and larger artery-to-vein anastomoses than Type II placentas, and proximate cord insertions were only observed in Type III. On the ultrasound scan at first diagnosis, small Type II twins were more growth-restricted. An AA anastomosis was detected in half of the Type III cases and in none of the Type II group. Signs of high-output cardiac strain were observed only in large Type III twins. In contrast, placental dichotomy was detected in nearly half of the Type II cases and only one Type III case.Conclusions: The presence of an AA anastomosis, signs of cardiac strain in the large twin, and proximate cord insertions suggested Type III sFGR, whereas placental dichotomy and a severe growth restriction were typically present in Type II. Prospective studies need to validate if these markers help prenatal differentiation between Type II and III sFGR. [ABSTRACT FROM AUTHOR]

Germinal matrix-intraventricular brain hemorrhage is mostly found in preterm neonates, but may also occur in term neonates. The aim of this study was to analyze the prevalence and severity of this type of hemorrhage in moderate and late preterm and early term neonates with intrauterine growth restriction. In the prospective analysis, 100 newborns were examined, i.e. 70 with intrauterine growth restriction and 30 as a control group. Study subjects were neonates from 32 0/7 to 38 6/7 gestational weeks. Body weight, body length, head circumference and ponderal index at birth were analyzed. Hemorrhage was assessed by cranial ultrasound using Papile classification. Out of 70 neonates with intrauterine growth restriction, germinal matrix-intraventricular hemorrhage was not found in 36 (51.43%) neonates, 31 (44.29%) had hemorrhage grade 1, and three (4.29%) had hemorrhage grade 2, which was statistically significant (p

AbstractBackground Absent end-diastolic flow (AEDF) in the umbilical artery (UA) worsens the already poor prognosis of growth-restricted fetuses (GRFs) in pregnancies complicated by early-onset preeclampsia with severe features (ESP).Method We assessed the correlation between the effect of maternal dexamethasone (Dex) on AEDF in the UA and perinatal outcomes, in 59 GRFs from EPS-complicated pregnancies. The maternal outcome was also evaluated.Results The mean maternal age at inclusion was 22.4 ± 5.9 years. Dex transiently restored EDF in the UA in 38 (64.4%) cases (trAEDF group), but in 21 (35.6%) patients, the flow was persistently absent (prAEDF group). The effect lasted up to the 4th day.The gestational age at diagnosis, number of days from admission until delivery, and fetal weight were significantly lower in the prAEDF group than in the trAEDF group (p .05).Conclusions The Dex no-effect on UA Doppler in GRFs with AEDF in the UA, in EPS-complicated pregnancies, can be a useful marker for a higher risk of proximal fetal deterioration, poor state at delivery, neonatal hypoxic complications, and worsening maternal condition, but not for perinatal mortality. The findings also highlight the alarmingly younger age of patients with EPS. Finally, all these pregnancies should be monitored in a complex multidisciplinary manner in tertiary referral units.Key messageThe effect of dexamethasone on absent end-diastolic flow in the umbilical artery in growth-restricted fetuses from pregnancies complicated by early-onset preeclampsia with severe features can be a useful prognostic factor for perinatal outcomes.

Objective: To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment., Methods: This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile)., Results: Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, p  < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, p  < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, p  = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, p  = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight., Conclusions: Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.

To evaluate the characteristics and outcomes of women who had never delivered vaginally and underwent a trial of labor after cesarean (TOLAC) of small for gestational age (SGA) neonates, and to identify risk factors for unplanned repeat cesarean delivery. A retrospective cohort study from two tertiary medical centers. All women undergoing a TOLAC with no prior vaginal delivery, delivering a singleton SGA neonate at term between 2005 and 2020 were included. Factors associated with successful vaginal delivery were examined by a multivariable analysis. Of the 255 women who met the inclusion criteria and underwent TOLAC, 72.2% delivered vaginally. In a multivariable analysis, maternal height [adjusted odds ratio (aOR) (95% CI): 1.10 (1.02–1.19), p = 0.012] and epidural administration [aOR (95% CI): 2.78 (1.0–7.73), p = 0.050] were positively independently associated with TOLAC success, and hypertensive disorders were negatively independently associated with TOLAC success [aOR (95% CI): 0.52 (0.004–0.74), p = 0.029]. The success rate of TOLAC among women with no prior vaginal delivery, delivering a SGA neonate is relatively high. Maternal height, hypertensive disorders, and epidural administration are independent factors associated with TOLAC success. Epidural administration is a modifiable factor and should be taken in consideration during TOLAC management. [ABSTRACT FROM AUTHOR]

Background: Intrauterine growth restriction (IUGR) refers to fetuses with an estimated ultrasonography weight below the 10% percentile. Hypoglycemia is a major concern in neonates with IUGR. Objective: To investigate the relationship between umbilical artery (UA) Doppler ultrasonography and neonate hypoglycemia and IUGR. Materials and Methods: This was a longitudinal follow-up study consisting of 114 neonates (gestational age of 28-40 wk) born with IUGR in the third trimester of pregnancy at Shahid Sadoughi Hospital, Yazd, Iran between May 2016 and October 2017. The neonates were assigned into three subgroups of normal UA Doppler, absent end-diastolic flow (EDF) in UA Doppler, and reverse EDF in UA Doppler. The blood glucose of the neonates was checked one, two, three, six, 12, 24 and 48 hr after birth, and the neonates were placed in the hypoglycemia or euglycemia groups according to guidelines. Results: Out of the 114 neonates included in the study, 75 (65.8%) had normal UA Doppler, 29 (25.4%) had absent EDF in UA Doppler, and 10 (8.8%) had reverse EDF in UA Doppler. There was a significant difference in the mean blood glucose in the first hr between the normal UA Doppler group and the reverse EDF in UA Doppler group (p < 0.01). Conclusion: Postnatal hypoglycemia in neonates with IUGR is associated with the result of UA Doppler ultrasonography during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose Uterine torsion (UT) in pregnancy is a rare condition in obstetric practice. It is defined as a rotation of the uterus of more than 45° around its long axis. Presentations are varied and, most of the time, this condition is recognized at laparotomy or cesarean section (CS). The aim of this study is to summarize the latest evidence about UT in pregnancy. Methods: A systematic research of the literature was conducted fetching all papers published from March 2006 to June 2020. We collected data regarding clinical features, treatment, and feto‐maternal outcomes. Finally, we reported data of a case of UT associated with intrauterine growth restriction (IUGR) diagnosed and treated at our institution. Results: According to our search strategy, 38 articles were included. In 66% of the cases, acute symptomatology was present at the onset, most frequently abdominal pain was reported. In one‐third of the cases, UT was diagnosed during CS without clinical suspicion. Only in two cases, including our case, IUGR was reported. Most (66%) of the cases presented a 180° torsion. In the majority of the cases, a CS was performed also with a deliberate or accidental posterior hysterotomy. One and six cases of maternal and fetal death were, respectively, reported. Conclusion: UT is an infrequent obstetric condition but should be considered in case of abdominal pain, vomiting, or shock presentation during pregnancy. It could lead to a reduction in uterine blood flow contributing to poor placental perfusion, even though more evidence is needed to clarify this link. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) and postnatal growth restriction are significant clinical dilemmas that contribute to short- and long-term morbidities for the most premature infants.Purpose: After a rise in NEC rates in a regional neonatal intensive care unit (NICU), improvement practices were implemented by an interdisciplinary quality improvement (QI) work group whose focus was initially on nutrition and growth. QI work was refocused to address both NEC and growth concurrently.Methods: Through various QI initiatives and with evolving understanding of NEC and nutrition, the work group identified and implemented multiple practices changes over 2-decade time span. A standardized tool was used to review each case of NEC and outcomes were continually tracked to guide QI initiatives.Local Findings: Focused QI work contributed to a significant reduction in NEC rates from 16.2% in 2007 to 0% in 2018 for inborn infants. Exclusive human milk diet was a critical part of the success. Postnatal growth outcomes initially declined after initial NEC improvement work. Improvement work that focused jointly on NEC and nutrition resulted in improved growth outcomes without impacting NEC.Implications For Practice: Use of historical perspective along with evolving scientific understanding can guide local improvement initiatives. Work must continue to optimize lactation during NICU hospitalization. More research is needed to determine impact of care practices on gastrointestinal inflammation including medication osmolality, probiotics, and noninvasive respiratory support. [ABSTRACT FROM AUTHOR]

Absent end-diastolic flow (AEDF) in the umbilical artery (UA) worsens the already poor prognosis of growth-restricted fetuses (GRFs) in pregnancies complicated by early-onset preeclampsia with severe features (ESP). We assessed the correlation between the effect of maternal dexamethasone (Dex) on AEDF in the UA and perinatal outcomes, in 59 GRFs from EPS-complicated pregnancies. The maternal outcome was also evaluated. The mean maternal age at inclusion was 22.4 ± 5.9 years. Dex transiently restored EDF in the UA in 38 (64.4%) cases (trAEDF group), but in 21 (35.6%) patients, the flow was persistently absent (prAEDF group). The effect lasted up to the 4th day. The gestational age at diagnosis, number of days from admission until delivery, and fetal weight were significantly lower in the prAEDF group than in the trAEDF group (p <.05). The same group had a significantly increased rate of fetal proximal deterioration, low APGAR scores, neonatal hypoxia, assisted ventilation, mild intraventricular haemorrhage (I/II), and respiratory distress syndrome, as well as maternal deterioration, especially in cases of resistant hypertension (p <.05). Although the rates of fetal acidemia and perinatal mortality in the prAEDF group were respectively three times and two times higher, the differences were not significant (p >.05). The Dex no-effect on UA Doppler in GRFs with AEDF in the UA, in EPS-complicated pregnancies, can be a useful marker for a higher risk of proximal fetal deterioration, poor state at delivery, neonatal hypoxic complications, and worsening maternal condition, but not for perinatal mortality. The findings also highlight the alarmingly younger age of patients with EPS. Finally, all these pregnancies should be monitored in a complex multidisciplinary manner in tertiary referral units. The effect of dexamethasone on absent end-diastolic flow in the umbilical artery in growth-restricted fetuses from pregnancies complicated by early-onset preeclampsia with severe features can be a useful prognostic factor for perinatal outcomes. [ABSTRACT FROM AUTHOR]

Under marginal nutritional conditions, growth in utero is related to subsequent growth and adult height. The aim of this research is to compare the young adult body size of women grouped by estimated duration of pregnancy relative to World War II. Subjects were 620 university students 18-25 years, for whom archival data for date of birth, age, height and weight were available; the BMI was calculated. Based on estimated time of pregnancy and birth relative to WWII, the women were grouped as follows: (1) pregnancy and birth before the war (n=203); (2) pregnancy before the war, birth during the war (n=54); (3) pregnancy and birth during the war (n=173); (4) pregnancy during the war, birth after the war (n=16); and (5) pregnancy and birth after the war (n=174). Heights of women born before and after WWII were significantly taller than heights of women born during the war. Though not significant, the height of women who were conceived before but born during the war was intermediate between those of women born before and during the war. The height of women conceived during the war but born after the war was similar to that of women conceived and born during the war. In contrast, BMIs and the distributions of women by weight status did not differ among the five pregnancy groups. The results suggested that heights of young adult women exposed in utero to the conditions of WWII (marginal nutritional status, maternal stress, among other factors) were shorter than women who were not exposed in utero to wartime conditions.

The gene RARRES3 uses an unexpected strategy to eliminate the parasite Toxoplasma gondii from human cells.

Toxoplasma gondii is an important human pathogen infecting an estimated one in three people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting T. gondii growth in human cells. Growth restriction is presumed to be due to the induction of interferon-stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impact T. gondii infection in human cells. In addition to IRF1, which likely acts through the induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts T. gondii infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting T. gondii infection, the limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFNγ-mediated immunity to T. gondii infection is a complex, multifactorial process.

Background: Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare autosomal recessive disorder characterized by severe pre‐ and postnatal growth restrictions, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. Previous studies have shown that MOPD II is associated with mutations in the pericentrin (PCNT) gene. Methods: We evaluated the clinical features of a 10‐year and 7‐month‐old Chinese girl with MOPD II. Subsequently, next‐generation sequencing and flow cytometry were performed to investigate genetic characteristics and the expression of PCNT protein respectively. Results: The patient presented with short stature, microcephaly, typical craniofacial features, teeth deformity, thrombocytosis, and a delayed bone age (approximately 7 years). No abnormality in growth hormone or insulin‐like growth factor 1 was detected. Notably, the patient was found to carry a novel homozygous PCNT mutation (c.6157G>T, p.Glu2053Ter), which was inherited from her healthy heterozygous parents. Meanwhile, significant deficiency of PCNT expression was identified in the patient. Conclusion: Our study identified a novel PCNT mutation associated with MOPD II, expanded the mutation spectrum of the PCNT gene and improved our understanding of the molecular basis of MOPD II. [ABSTRACT FROM AUTHOR]

PurposeIn Scandinavia, delivery of a first-born son elevates the risk of preterm delivery and intrauterine growth restriction of the next-born infant. External validity of these results remains unclear. We test this hypothesis for preterm delivery and growth restriction using the linked California birth cohort file. We examined the hypothesis separately by race and/or ethnicity.MethodsWe retrieved data on 2,852,976 births to 1,426,488 mothers with at least two live births. Our within-mother tests applied Cox proportional hazards (preterm delivery, defined as less than 37 weeks gestation) and linear regression models (birth weight for gestational age percentiles).ResultsFor non-Hispanic whites, Hispanics, Asians, and American Indian and/or Alaska Natives, analyses indicate heightened risk of preterm delivery and growth restriction after a first-born male. The race-specific hazard ratios for preterm delivery range from 1.07 to 1.18. Regression coefficients for birth weight for gestational age percentile range from -0.73 to -1.49. The 95% confidence intervals for all these estimates do not contain the null. By contrast, we could not reject the null for non-Hispanic black mothers.ConclusionsWhereas California findings generally support those from Scandinavia, the null results among non-Hispanic black mothers suggest that we do not detect adverse outcomes after a first-born male in all racial and/or ethnic groups.

Abstract Background Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare autosomal recessive disorder characterized by severe pre‐ and postnatal growth restrictions, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. Previous studies have shown that MOPD II is associated with mutations in the pericentrin (PCNT) gene. Methods We evaluated the clinical features of a 10‐year and 7‐month‐old Chinese girl with MOPD II. Subsequently, next‐generation sequencing and flow cytometry were performed to investigate genetic characteristics and the expression of PCNT protein respectively. Results The patient presented with short stature, microcephaly, typical craniofacial features, teeth deformity, thrombocytosis, and a delayed bone age (approximately 7 years). No abnormality in growth hormone or insulin‐like growth factor 1 was detected. Notably, the patient was found to carry a novel homozygous PCNT mutation (c.6157G>T, p.Glu2053Ter), which was inherited from her healthy heterozygous parents. Meanwhile, significant deficiency of PCNT expression was identified in the patient. Conclusion Our study identified a novel PCNT mutation associated with MOPD II, expanded the mutation spectrum of the PCNT gene and improved our understanding of the molecular basis of MOPD II.

The effect of dilute solute additions on growth restriction in Cu-, Al-, Mg- and Ti-based binary and ternary alloys was assessed by means of the heuristic growth restriction parameter (β) modelling framework. The CALPHAD (calculation of phase diagrams) methodology was used to calculate β values from the m and k values, at first approximation, as well as from the liquid-to-solid fraction to obtain true β values. Grain size values from the literature were plotted against the corresponding true β values, showing a negative or inverse correlation between the two.

Grain refinement is of importance for metallic materials since it provides multiple benefits, such as improved castability, reduced casting defects and improved mechanical properties. From extensive research carried out in the past decades, it has been widely accepted that solute is one of the crucial factors for achieving grain refinement. However, grain refinement is a complex phenomenon, depending on not only solutes in the melt to provide growth restriction but also the physical and chemical nature of the nucleant particles (either endogenous or exogenous). Although significant progress has been made on the subject, some critical questions still remain open, and a comprehensive understanding of the mechanisms of solute effect on grain refinement is still desirable. In this paper, we present an overview of the solute effect on grain refinement based on our recent advances made in the LiME Research Hub. This covers the effect of solute on nucleation potency of nucleant particles due to interfacial segregation, columnar to equiaxed transition (CET), growth restriction and eventually on the overall grain refinement.

Background: Close monitoring of growth pattern in preterm neonates is essential to identify any deviations from the normal pattern. But, there is no international consensus regarding how the growth of preterm neonates should be monitored or what constitutes the ideal pattern of growth in these premature infants. Objective: To compare the incidence of IUGR & EUGR in preterm neonates ≤32 weeks gestational age based on Fenton 2013 growth curves and Intergrowth-21 growth standards. Design: Retrospective Cohort Study. Study site: Tertiary care neonatal unit with nearly 1000 admissions to the neonatal unit. Participants: All newborns with gestational age ≤32 weeks (230 6/7 days) admitted to the NICU within 24 h of birth over a period of 3 years from 1 January 2015 to 31 December 2017. Results: Out of 821 neonates born during the study period 603 were included. The mean birth weight, length, and head circumference were 1356.683 ± 335.91 g, 39.244 ± 3.124 cm, and 27.819 ± 1.906 cm, respectively. The mean discharge weight, length, and head circumference were 1550.70 ± 185.122 g, 41.606 ± 2.026 cm, and 29.398 ± 1.221cm, respectively. The proportion of infants identified as IUGR at birth with respect to weight, length, and head circumference on both the charts was 15.1, 14.4, and 9%, respectively. The proportion of infants identified as EUGR at discharge with respect to weight, length, and head circumference on both the charts was 45.7, 29.8, and 32.3%, respectively. Conclusion: The proportion of infants identified as IUGR at birth and EUGR at discharge differed on the usage of Intergrowth charts (Birth reference and postnatal) in comparison to Fenton growth charts. The infants identified as IUGR at birth by Intergrowth charts and not by Fenton growth charts had higher incidence of morbidities. [ABSTRACT FROM AUTHOR]

Introduction: A total of 161 million children a year are growth restricted, leading to a 47% increased risk of chronic disease in adulthood. Physical activity (PA) reduces the risk of mortality from chronic disease. The purpose of the present investigation was to determine the effect of a PA intervention (wheel running) on cardiac and skeletal muscle capacities in gestational (GUN) and postnatal (PUN) growth-restricted mice as compared with nonrestricted controls (CON). Methods: A low-protein cross-fostering FVB mouse model was used to induce growth restriction during gestation and the first 21 d of postnatal life.Mouse pups were recovered on a healthy diet until mature and provided wheel access for 3 wk. At completion of the PA intervention, mice underwent maximal exercise testing on a treadmill, echocardiography, and skeletal muscle histology. Results: After the PA intervention, CON mice had a 45% improvement in maximal exercise capacity (P = 0.0390) because of cardiac and skeletalmuscle adaptations, but GUN and PUN mice did not. Alarmingly, PUN female mice exposed to wheels had 11.45% lower left ventricular volume (P = 0.0540) and 18% lower left ventricle area (P = 0.0585), with blood flow velocities indicative of cardiac fibrosis (GUN had elevated isovolumetric contraction time P = 0.0374;GUN females and PUNmales had longer isovolumetric relaxation time P = 0.0703). PUN male mice had mixed skeletal muscle responses with an oxidative shift in the diaphragm (P = 0.0162) but a glycolytic shift in the extensor digitorumlongus (P = 0.0647). PUN female mice had a glycolytic shift in the soleus after wheel running. Conclusions: Unexpectedly, growth-restricted mice were nonresponders to a PA intervention and displayed negative cardiac outcomes. [ABSTRACT FROM AUTHOR]

Objective: Both small for gestational age (SGA) birthweight and pregnancies complicated by maternal hypertension (HTN) are independently associated with poorer childhood learning outcomes, however the relative contribution of each remains unknown.Study Design: A retrospective cohort was created in which 2014-2017 third grade Rhode Island Department of Education data were linked to Rhode Island Department of Health birth certificate data. The study population was composed of non-anomalous, singleton births between 22- and 42-weeks' gestation. Reading and math proficiency were compared among four groups: 1) appropriate for gestational age (AGA) and no maternal HTN (referent), 2) AGA with HTN, 3) SGA without HTN and 4) SGA with HTN.Main Outcome Measures: Bivariable and multivariable log-binomial regression were used to examine the association between subject proficiency and pregnancy complication, adjusting for potential confounders.Results: Of the 23,097 who met inclusion criteria, 1004 (4%) were AGA with HTN, 1575 (7%) were SGA without HTN and 176 (1%) were SGA with HTN. Overall, when adjusted for maternal age, gestational age, sex and socioeconomic factors, only children born SGA without HTN had reduced reading proficiency (relative risk (RR) 0.86 95% confidence interval (CI) 0.78, 0.92) and math proficiency (RR 0.88 95% CI 0.82, 0.94) compared to children born AGA without HTN.Conclusion: In a diverse, statewide cohort, only SGA without HTN was associated with lower reading and math proficiency compared to uncomplicated pregnancies. This suggests that only decreased fetal growth from causes other than HTN is associated with risk of poorer school-age outcomes, and has implications for early resource allocation. [ABSTRACT FROM AUTHOR]

Objective: Placental growth factor (PlGF) has shown promise in identification of placental fetal growth restriction (FGR). We aimed to investigate the association between PlGF and sonographic markers of placental dysfunction and assess its ability to diagnose FGR secondary to maternal vascular malperfusion (MVM).Study Design: A retrospective study of singleton pregnancies with small for gestational age (SGA) fetuses, who had PlGF testing at 16-36 weeks. Fetuses with major chromosomal and/or structural anomalies and pregnancies with missing outcomes were excluded. Sonographic characteristics, perinatal outcomes and placental histopathology were compared between pregnancies with normal and low PlGF (<10th percentile for gestational age). The diagnostic accuracy of PlGF for prediction of MVM was calculated.Results: 130 fetuses met inclusion criteria. Compared to normal PlGF (n = 65), pregnancies with low PlGF (n = 65) were associated with an estimated fetal weight < 5th centile (73.8% (48) vs 53% (35), respectively, p = 0.01), abnormal uterine, umbilical and MCA Dopplers (p = 0.001 for all), fetal demise (18.8% (12) vs 0% respectively, p = 0.01) and preterm delivery (100% (65) vs 39% (59), respectively, p < 0.001) . Low PlGF had a 70.1% (58.6-80.0) sensitivity and a 79.6% (64.7-90.2) specificity for identifying MVM, with an AUC of 0.73 (0.63-0.84). Positive and negative predictive values were 85.7% (76.8-91.2) and 60.3% (51.2-68.9), respectively. PlGF outperformed other parameters of placental FGR (uterine, umbilical artery, middle cerebral artery and abdominal circumference < 5th centile), in isolation and when combined.Conclusion: PlGF is a useful tool to aid in the diagnosis of placental FGR secondary to MVM. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) can result in developmental defects that include growth restriction, craniofacial anomalies, and cognitive behavioral deficits, though the presence and severity of these adverse outcomes can vary dramatically among exposed individuals. Preclinical animal models have demonstrated that the dose and timing of PAE account for much, but not all, of this phenotypic variation, suggesting that additional factors mitigate the effects of PAE. Here, we used a mouse model to investigate whether maternal age modulates the effects of PAE on the severity and variation in offspring growth and craniofacial outcomes. Methods: Nulliparous C57BL/6N dams received either an intraperitoneal injection of ethanol (EtOH) or vehicle solution on gestational day 7.5. Dams were divided into four groups: (1) EtOH‐treated young dams (6 to 10 weeks); (2) control young dams; (3) EtOH‐treated old dams (6 to 7 months); and (4) old control dams. Neonate offspring growth restriction was measured through body mass and organ‐to‐body mass ratios, while skeletal craniofacial features were imaged using micro‐CT and analyzed for size, shape, and variation. Results: PAE and advanced maternal age each increased the risk of low birthweight and growth restriction in offspring, but these factors in combination changed the nature of the growth restriction. Similarly, both PAE and advanced maternal age individually caused changes to craniofacial morphology such as smaller skull size, dysmorphic skull shape, and greater skull shape variation and asymmetry. Interestingly, while the combination of PAE and advanced maternal age did not affect mean skull shape or size, it significantly increased the variation and asymmetry of those measures. Conclusion: Our results indicate that maternal age modulates the effects of PAE, but that the effects of this combination on offspring outcomes are more complex than simply scaling the effects of either factor. [ABSTRACT FROM AUTHOR]

ObjectivesOur aim was to determine if uterine artery (UtA) Doppler studies would risk-stratify women with abnormal serum analytes on prenatal genetic screening into those at baseline and increased risk for preeclampsia and small-for-gestational age (SGA).Study designThis retrospective cohort study examined outcomes of patients with ⩾one abnormal analyte (PAPP-A3.0, AFP>2.5, inhibin>2.0, or unconjugated estriol1.6); preeclampsia occurred in 16 (12%) and 26 (20%) delivered a SGA neonate. Abnormal UtA Doppler PI increased the likelihood of a composite outcome of preeclampsia or SGA from 27% to 71% (LR 6.48 (2.93, 14.30)); a negative UtA Doppler PI reduced the likelihood to 18% (LR 0.57 (0.42, 0.78)). Abnormal UtA Doppler PI increased the likelihood of a more severe composite outcome of preterm preeclampsia or IUGR from 11% to 39% (LR 5.49 (3.03, 9.97)); a negative UtA Doppler study reduced the likelihood to 4% (LR 0.35 (0.16, 0.80)).ConclusionsIn patients with abnormal serum analytes, abnormal UtA Doppler PI is significantly associated with preeclampsia or SGA and improves the prediction of these adverse outcomes by 9-15-fold. Providers can incorporate UtA Doppler PI into an abbreviated surveillance regimen; they can be reassured that a normal study markedly decreases the risk of a severe early adverse outcome.