CONTEXT: Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse neurologic developmental outcomes during the school-age years of life. OBJECTIVE:To estimate the effect of IUGR on cognition and behavior in school-aged children.DATA SOURCES: Medline, Embase, and PsycINFO were searched for English-language articles published after 1980.DATA SELECTION We included case-control studies reporting cognitive and/or behavioral data of children who had IUGR and were evaluated afterfifth birthday. DATA EXTRACTION:Cognitive data from 15 studies and behavioral data from 6 studies were selected with a total of 1559 cases and 1630 controls. The cognitive scores and behavioral outcomes were extracted. RESULTS:The controls had significantly higher cognitive scores than the children with IUGR (standardized mean difference [SMD] -0.38, 95% confidence interval [CI] -0.51 to -0.25, P < .00001). The IQ scores of the IUGR group were not significantly correlated with mean birth weight and gestational age (P > .05). Five trials were included in the behavioral outcomes trial, the behavior scores were significantly different between the groups with and without IUGR (SMD 0.31, 95% CI 0.13 to 0.48, P = .001). The incidence of attention-deficit/ hyperactivity disorder (ADHD) was not significantly different between 2 groups (P = .11). LIMITATIONS:The number of studies that assessed behavioral and ADHD outcome is small. CONCLUSIONS:The findings demonstrate that IUGR is associated with lower cognitive scores in school-age children. However, further large-scale trials are needed to assess the effects of IUGR on the outcome of behavioral disorder and ADHD.Neonatal Division, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China Dr P. Chen conceptualized and designed the study, and reviewed and revised the manuscript; Dr J. Chen carried out the initial analyses, and drafted the initial manuscript; Drs Bo and Luo collected data, and critically reviewed the manuscript; and all authors approved the fi nal manuscript as submitted and agree to be accountable for all aspects of the work. By 2 to 3 years after birth, infants with IUGR will undergo catch-up growth of both the body and head 3 ; however, approximately 10% of IUGR cases do not achieve catch-up growth and exhibit persistent growth delay. 4 Many studies have shown that IUGR is associated with increased neonatal morbidity and mortality as well as cardiovascular disease, insulin resistance, diabetes mellitus type 2, dyslipidemia, and end-stage renal disease in adulthood. In addition, numerous large-scale follow-up studies have shown that IUGR is associated with significant neurodevelopmental impairment across a range of outcomes in children. [5][6][7] The effects of IUGR persist beyond the neonatal period and may have a profound impact on childhood development. To date, neurodevelopment in school-age children with IUGR has received comparatively little attention. Here, we present a meta-analysis and systematic review...
BackgroundIntrauterine growth restriction (IUGR) is associated with perinatal morbidity and mortality. Several clinical trials have reported L-arginine and sildenafil citrate had effect on intrauterine growth restriction fetuses. A meta-analysis of available randomized controlled trials (RCTs) was conducted to investigate the effects of L-arginine and sildenafil citrate on major clinical outcomes of IUGR fetuses.MethodsSystematically searched Medline, Embase, the Cochrane Library, and Clinical Trials, references of retrieved articles, and conference proceedings from 1960 to 2015. We included randomized controlled trials assessing the effects of L-arginine and sildenafil citrate on IUGR. Outcomes analyzed were the birth weight, gestational age at labor, Apgar score at 1and 5 min, the ratio of NRDS, the ratio of ICH and neonatal death, etc.ResultsTen trials were included. Nine trials (576 patients) compared L-arginine with either placebo or no intervention. In the L-arginine treatment groups of the L-arginine trials, there was a significant increase in fetal birth weight (SMD 0.41, 95 % CI [0.24,0.58]), gestational age (SMD 0.30, 95 % CI [0.07,0.54]); L-arginine treatment group have a significant reduction in the ratio of neonatal respiratory distress syndrome (P = 0.009), intracranial hemorrhage of fetuses (P = 0.002), but the number of included studies and people on these outcomes are small. As only one trial (41 patients) compared sildenafil citrate with placebo, it was too small for reliable conclusions about possible differential effects could be drawn.ConclusionsThe results of this meta-analysis showed that L-arginine increased birth weight and prolonged gestational age at labor of IUGR fetuses. However, further large-scale RCTs are needed to adequately assess the effect of L-arginine and Sildenafil citrate on clinical outcomes, because the number of study may be small.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-1009-6) contains supplementary material, which is available to authorized users.
In humans, malnutrition during pregnancy results in intrauterine growth restriction (IUGR) and an increased risk of neurological morbidities; altered miRNA characteristics have been suggested to contribute to IUGR neurological pathogenesis. A miRNA microarray was used to identify differentially expressed miRNA molecules in the hippocampi of rats with IUGR. Five of the molecules in question were selectively validated using real-time PCR in rats with IUGR. We then investigated the role of miR-199a-5p in hippocampal pathology. Bioinformatics analysis results suggested that TNF-α, caspase-3 and SIRT1 were potential targets of miR-199a-5p. Changes in PI3K, SIRT1 and caspase-3 protein expressions levels in the hippocampus were confirmed by Western blot analysis (all P < 0.05). Studies using the pheochromocytoma cell line PC12 cells and primary neurons demonstrated that miR-199a-5p modulated PI3K, caspase-3 and SIRT1 expression. Additionally, there was an inverse correlation between miR-199a-5p and caspase-3 expression, though dual-luciferase reporter assays showed that caspase-3 is not a target of miR-199a-5p. We conclude that IUGR affects hippocampal miRNAs characteristics. Our results also indicated that aberrantly high expression levels of miR-199a-5p may play an important role in the pathogenesis of IUGR by regulating SIRT1 and PI3K.
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