Late Enteral Feedings Are Associated with Intestinal Inflammation and Adverse Neonatal Outcomes.
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ABSTRACT:
SUBMITTER: Konnikova Y
PROVIDER: S-EPMC4501691 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal-fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition.
| S-EPMC6015905 | biostudies-other
Project description:PurposeMaternal anemia is a significant risk factor for maternal morbidity and mortality, increasing risk of preterm birth, intrauterine growth restriction, stillbirth, and death. Moderate and severe anemia in pregnancy is defined as hemoglobin (Hb) <10 g/dl and Hb < 7 g/dl, respectively. We aimed to characterize the association of maternal anemia with maternal, neonatal, and placental outcomes in a resource-limited setting.MethodsData were collected from a prospective cohort of 352 pregnant women at a tertiary academic Ugandan hospital. One hundred and seventy-six (50%) of women were living with HIV. Hemoglobin was measured in labor, and placentas were collected postpartum. Maternal outcomes included mode of delivery, hemorrhage, blood transfusion, intensive care unit admission, and maternal mortality. Neonatal outcomes included gestational age at delivery, birthweight, stillbirth, and neonatal mortality. Placental descriptors included weight and thickness. Categorical variables were analyzed using Chi-squared and Fisher's exact tests.ResultsHemoglobin < 10 g/dl, was present in 17/352 (5%) of women. Significantly more women with moderate or severe anemia were HIV-infected: 14/17 (82%) versus 162/335 (48%) (p = .006). Blood transfusions (2/17, 12% versus 5/335, 2%, p = .04) and neonatal deaths (2/17, 12% versus 9/335, 3%, p = .01) were more common in the anemia group. Placental thickness was lower in the anemia group (1.4 cm versus 1.7 cm, p = .04).ConclusionsModerate and severe anemia was associated with maternal HIV infection, maternal blood transfusion, neonatal death, and decreased placental thickness. The overall rate of moderate and severe anemia among this cohort was lower than previously reported.
| S-EPMC10419325 | biostudies-literature
Project description:Trauma is a leading cause of morbidity and mortality. It is unclear why some trauma victims follow a complicated clinical course and die, while others, with apparently similar injury characteristics, do not. Interpatient genomic differences, in the form of single nucleotide polymorphisms (SNPs), have been associated previously with adverse outcomes after trauma. Recently, we identified seven novel SNPs associated with mortality following trauma. The aim of the present study was to determine if one or more of these SNPs was also associated with worse clinical outcomes and altered inflammatory trajectories in trauma survivors. Accordingly, of 413 trauma survivors, DNA samples, full blood samples, and clinical data were collected at multiple time points in the first 24 h and then daily over 7 days following hospital admission. Subsequently, single-SNP groups were created and outcomes, such as hospital length of stay (LOS), ICU LOS, and requirement for mechanical ventilation, were compared. Across a broad range of Injury Severity Scores (ISS), patients carrying the rs2065418 TT SNP in the metallophosphoesterase domain-containing 2 (MPPED2) gene exhibited higher Marshall MODScores vs. the control group of rs2065418 TG/GG patients. In patients with high-severity trauma (ISS ≥ 25, n = 94), those carrying the rs2065418 TT SNP in MPPED2 exhibited higher Marshall MODScores, longer hospital LOS (21.8 ± 2 days), a greater requirement for mechanical ventilation (9.2 ± 1.4 days on ventilator, DOV), and higher creatinine plasma levels over 7 days vs. the control group of rs2065418 TG/GG high-severity trauma patients (LOS: 15.9 ± 1.2 days, p = 0.03; DOV: 5.7 ± 1 days, p = 0.04; plasma creatinine; p < 0.0001 MODScore: p = 0.0003). Furthermore, rs2065418 TT patients with ISS ≥ 25 had significantly different plasma levels of nine circulating inflammatory mediators and elevated dynamic network complexity. These studies suggest that the rs2065418 TT genotype in the MPPED2 gene is associated with altered systemic inflammation, increased organ dysfunction, and greater hospital resource utilization. A screening for this specific SNP at admission might stratify severely injured patients regarding their lung and kidney function and clinical complications.
| S-EPMC6857553 | biostudies-literature
Project description:Sterile intra-amniotic inflammation is commonly observed in patients with spontaneous preterm labor, a syndrome that commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. However, the mechanisms leading to sterile intra-amniotic inflammation are poorly understood and no treatment exists for this clinical condition. Herein, we investigated whether the alarmin S100B could induce sterile intra-amniotic inflammation by activating the NLRP3 inflammasome, and whether the inhibition of this pathway could prevent preterm labor/birth and adverse neonatal outcomes. We found that the ultrasound-guided intra-amniotic administration of S100B induced a 50% rate of preterm labor/birth and a high rate of neonatal mortality (59.7%) without altering the fetal and placental weights. Using a multiplex cytokine array and immunoblotting, we reported that S100B caused a proinflammatory response in the amniotic cavity and induced the activation of the NLRP3 inflammasome in the fetal membranes, indicated by the upregulation of the NLRP3 protein and increased release of active caspase-1 and mature IL-1β. Inhibition of the NLRP3 inflammasome via the specific inhibitor MCC950 prevented preterm labor/birth by 35.7% and reduced neonatal mortality by 26.7%. Yet, inhibition of the NLRP3 inflammasome at term did not drastically obstruct the physiological process of parturition. In conclusion, the data presented herein indicate that the alarmin S100B can induce sterile intra-amniotic inflammation, preterm labor/birth, and adverse neonatal outcomes by activating the NLRP3 inflammasome, which can be prevented by inhibiting such a pathway. These findings provide evidence that sterile intra-amniotic inflammation could be treated by targeting the NLRP3 inflammasome.
| S-EPMC6497524 | biostudies-literature
Project description:BackgroundAdolescents have physical, social and psychological characteristics that are different from adults. Adolescent pregnancy results in pregnancy and childbirth complications- an area neglected in developing countries like Ethiopia. This study, therefore, was conducted to assess the adverse neonatal outcomes of adolescent pregnancy in Northwest Ethiopia.MethodsInstitutional-based study was conducted in East Gojjam zone, Northwest Ethiopia. A total of 374 adolescent (15-19 years) and 760 adult (20-34 years) women were included in this study. Data were collected among women who came to randomly selected health facilities in East Gojjam zone. Data were collected by trained research assistants using a structured data collection questionnaire. Descriptive statistics, chi-square test, and Student's t-tests were utilized. Bivariate and multivariable logistic regression analysis were employed to adjust for confounding factors of adverse neonatal outcomes. Statistical significance was declared when the p-value was less than 0.05.ResultsHigher proportion of adolescent than adult women were from rural area (57.2% vs 44.7%), were not married (5.1% vs 1.7%), were pregnant for the first time (91.7% vs 34.1%), didn't attend antenatal care (ANC) follow-up (12% vs 4.5%), and had late initiation of ANC follow-up. After adjusting for known confounding factors, the odds of low birth weight (LBW) was higher among adolescents than adult women (AOR 2.14; 95% CI, 1.36, 3.36, p-value = 0.001). Similarly, the odds of preterm birth was higher among adolescents than adult women (AOR 1.65; 95% CI, 1.09, 2.49, p-value = 0.017). There was no statistically significant difference in the rate of low Apgar score at first and five minutes after birth and neonatal Intensive Care Unit (ICU) admission between babies born from adolescent and adult women.ConclusionsAdolescent women were less likely to receive ANC service. Babies born from adolescent women are at higher odds of adverse neonatal outcomes like LBW and preterm birth than babies born from adult women. Use of community- and health facility-based intervention programs that can prevent adolescent pregnancy and reduce adverse neonatal outcomes among adolescent girls is recommended.
| S-EPMC6564016 | biostudies-literature
Project description:PurposeTo determine if intestinal alkaline phosphatase (IAP) decreases intestinal injury resulting from experimentally induced necrotizing enterocolitis (NEC). We hypothesized that IAP administration prevents the initial development of NEC related intestinal inflammation.MethodsPre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day 1 of life. Pre-term pups were exposed to intermittent hypoxia and formula containing LPS to induce NEC. Select NEC pups were given 40, 4 or 0.4 units/kg of bovine IAP (NEC+IAP40u, IAP4u or IAP0.4u) enterally, once daily. Ileal sections were evaluated by real-time PCR (qRT-PCR) for IAP, iNOS, IL-1β, IL-6, and TNF-α mRNA and immunofluorescence for 3-nitrotyrosine (3-NT).ResultsExperimentally induced NEC decreased IAP mRNA expression by 66% (p ≤ 0.001). IAP supplementation increased IAP mRNA expression to control. Supplemental enteral IAP decreased nitrosative stress as measured by iNOS mRNA expression and 3-NT staining in the NEC stressed pups (p ≤ 0.01), as well as decreased intestinal TNF-α mRNA expression. In addition, IAP decreased LSP translocation into the serum in the treated pups.ConclusionsWe conclude that enterally administered IAP prevents NEC-related intestinal injury and inflammation. Enteral IAP may prove a useful strategy in the prevention of NEC in preterm neonates.
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Project description:Neuroticism is not only associated with affective disorders but also with certain somatic health problems. However, studies assessing whether neuroticism is associated with adverse obstetric or neonatal outcomes are scarce. This observational study comprises first-time mothers (n = 1969) with singleton pregnancies from several cohorts based in Uppsala, Sweden. To assess neuroticism-related personality, the Swedish universities Scales of Personality was used. Swedish national health registers were used to extract outcomes and confounders. In logistic regression models, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the outcomes by an increase of 63 units of neuroticism (equalling the interquartile range). Analyses were adjusted for maternal age, educational level, height, body mass index, year of delivery, smoking during pregnancy, involuntary childlessness, and psychiatric morbidity. Main outcomes were mode of delivery, gestational diabetes mellitus, gestational hypertension, preeclampsia, induction of delivery, prolonged delivery, severe lacerations, placental retention, postpartum haemorrhage, premature birth, infant born small or large for gestational age, and Apgar score. Neuroticism was not independently associated with adverse obstetric or neonatal outcomes besides gestational diabetes. For future studies, models examining sub-components of neuroticism or pregnancy-specific anxiety are encouraged.
| S-EPMC6820798 | biostudies-other
Project description:To date, studies of the relationship between antenatal glucocorticoids (AGC) and neonatal inflammation in preterm newborns have been largely limited to umbilical cord blood specimens.To explore the association between exposure to antenatal glucocorticoids and concentrations of inflammation-related proteins in whole blood collected from very preterm newborns at multiple times during the first postnatal month.We measured the protein concentrations on postnatal day 1 (N=1118), day 7 (N=1138), day 14 (N=1030), day 21 (N=936) and day 28 (N=877) from infants born before the 28th week of gestation and explored the relationship between antenatal steroid receipt and protein concentrations in the highest and lowest quartiles. The creation of multinomial logistic regression models (adjusted for potential confounders) allowed us calculate odds ratios and 95% confidence intervals.Twenty of 420 assessments [21 (proteins)×2 (exposure levels: partial and full)×2 (quartile levels: top and bottom)×5 (days)] were statistically significant without any cohesive pattern.Among infants born before 28 weeks of gestational age, neither full, nor partial courses of antenatal glucocorticoids have a sustained anti-inflammatory effect.
| S-EPMC5067239 | biostudies-other
Project description:Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. Using a model of LOS, we found that components of the developing microbiome were both necessary and sufficient to prevent LOS. Maternal antibiotic exposure that eradicated or enriched transmission of Lactobacillus murinus exacerbated and prevented disease, respectively. Prophylactic administration of some, but not all Lactobacillus spp. was protective, as was administration of Escherichia coli. Intestinal oxygen level was a major driver of colonization dynamics, albeit via mechanisms distinct from those in adults. These results establish a link between neonatal dysbiosis and LOS, and provide a basis for rational selection of probiotics that modulate primary succession of the microbiome to prevent disease.
| S-EPMC7250008 | biostudies-literature
Project description:BackgroundAntenatal women experience an increased level of mood and anxiety symptoms, which have negative effects on mothers' mental and physical health as well as the health of their newborns. The relation of maternal depression and anxiety in pregnancy with neonate outcomes is well-studied with inconsistent findings. However, the association between antenatal mood instability (MI) and neonatal outcomes has not been investigated even though antenatal women experience an elevated level of MI. We sought to address this gap and to contribute to the literature about pregnancy neonate outcomes by examining the relationship among antenatal MI, depression, and anxiety and neonatal outcomes.MethodsA prospective cohort of women (n = 555) participated in this study at early pregnancy (T1, 17.4 ± 4.9 weeks) and late pregnancy (T2, 30.6 ± 2.7 weeks). The Edinburgh Postnatal Depression Scale (EPDS) was used to assess antenatal depressive symptoms, anxiety was measured by the EPDS anxiety subscale, and mood instability was measured by a visual analogue scale with five questions. These mood states together with stress, social support, as well as lifestyle were also examined in relation to neonatal outcomes using chi-square tests and logistic regression models.ResultsMood instability, depression, and anxiety were unrelated to adverse neonatal outcomes. Only primiparous status was associated with small for gestational age after Bonferroni correction.ConclusionsWe report no associations between antenatal mood symptoms including MI, depression, and anxiety and neonatal outcomes. More studies are required to further explore the relationship between antenatal mood instability, depression, and anxiety and neonatal outcomes.
| S-EPMC8385792 | biostudies-literature