Cord Blood Cytokine Levels Correlate With Types of Placental Pathology in Extremely Preterm Infants.
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ABSTRACT:
SUBMITTER: Zein H
PROVIDER: S-EPMC7991101 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo compare short-term outcomes after placental transfusion (delayed cord clamping (DCC) or umbilical cord milking (UCM)) versus immediate cord clamping among extremely preterm infants.DesignRetrospective study.SettingThe Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network registry.PatientsInfants born <29 weeks' gestation in 2016 or 2017 without congenital anomalies who received active treatment after delivery.Intervention/exposureDCC or UCM.Main outcome measuresPrimary outcomes: (1) composite of mortality or major morbidity by 36 weeks' postmenstrual age (PMA); (2) mortality by 36 weeks PMA and (3) composite of major morbidities by 36 weeks' PMA. Secondary composite outcomes: (1) any grade intraventricular haemorrhage or mortality by 36 weeks' PMA and (2) hypotension treatment in the first 24 postnatal hours or mortality in the first 12 postnatal hours. Outcomes were assessed using multivariable regression, adjusting for mortality risk factors identified a priori, significant confounders and centre as a random effect.ResultsAmong 3116 infants, 40% were exposed to placental transfusion, which was not associated with the primary composite outcome of mortality or major morbidity by 36 weeks' PMA (adjusted OR (aOR) 1.26, 95% CI 0.95 to 1.66). However, exposure was associated with decreased mortality by 36 weeks' PMA (aOR 0.71, 95% CI 0.55 to 0.92) and decreased hypotension treatment in first 24 postnatal hours (aOR 0.66, 95% CI 0.53 to 0.82).ConclusionIn this extremely preterm infant cohort, exposure to placental transfusion was not associated with the composite outcome of mortality or major morbidity, though there was a reduction in mortality by 36 weeks' PMA.Trial registration numberNCT00063063.
| S-EPMC7736256 | biostudies-literature
Project description:Background: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life.Study design: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated.Results: Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age.Conclusion: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD).
| S-EPMC5841757 | biostudies-literature
Project description:Delayed cord clamping has been shown to decrease the need for transfusion in preterm neonates, but may delay resuscitation. The aim of this study was to determine whether umbilical cord milking compared with immediate cord clamping in extremely preterm deliveries reduces the need for neonatal red blood cell transfusion.Women admitted to a tertiary care center and expected to deliver between 24 to 28 completed weeks of gestation were randomized to cord milking before clamping or immediate cord clamping. The primary outcome was the risk of neonatal transfusion, reported as risk ratio (RR) and 95% confidence interval (CI).Of 113 women who were enrolled and randomized, 56 were assigned to cord milking with 36 remaining eligible and completing the study and 57 were assigned to the control group with 39 remaining eligible and completing the study. Albeit not statistically significant, neonates in the cord milking group were less likely to require transfusion compared with those in the control group (RR: 0.86; 95% CI: 0.73 to 1.0). Neonates whose cords were milked had higher hematocrits at birth (P=0.004) and were less likely to develop an intraventricular hemorrhage (P=0.0195).Milking the umbilical cord of a preterm neonate is an easy intervention with the potential to improve perinatal outcomes. Our results suggest that milking of the cord increases the neonate's initial hematocrit and may lessen the need for transfusion in the neonatal period. The observed reduction in the incidence of intraventricular hemorrhage may have important long-term implications that warrant further study.
| S-EPMC3916936 | biostudies-literature
Project description:Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1β, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16-2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985-1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.
| S-EPMC8592443 | biostudies-literature
Project description:BackgroundUnderstanding underlying mechanisms of neurodevelopmental impairment following preterm birth may enhance opportunities for targeted interventions. We aimed to assess whether placental DNA methylation of selected genes affected early neurological functioning in preterm infants.MethodsWe included 43 infants, with gestational age <30 weeks and/or birth weight <1,000 g and placental samples at birth. We selected genes based on their associations with several prenatal conditions that may be related to poor neurodevelopmental outcomes. We determined DNA methylation using pyrosequencing, and neurological functioning at 3 months post-term using Prechtl's General Movement Assessment, including the Motor Optimality Score-Revised (MOS-R).ResultsTwenty-four infants had atypical MOS-R, 19 infants had near-optimal MOS-R. We identified differences in average methylation of NR3C1 (encoding for the glucocorticoid receptor) [3.3% (95%-CI: 2.4%-3.9%) for near-optimal vs. 2.3% (95%-CI: 1.7%-3.0%), p = 0.008 for atypical], and at three of the five individual CpG-sites. For EPO, SLC6A3, TLR4, VEGFA, LEP and HSD11B2 we found no differences between the groups.ConclusionHypomethylation of NR3C1 in placental tissue is associated with poorer neurological functioning at 3 months post-term in extremely preterm infants. Alleviating stress during pregnancy and its impact on preterm infants and their neurodevelopmental outcomes should be further investigated.
| S-EPMC9198301 | biostudies-literature
Project description:OBJECTIVE:To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1-binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties. STUDY DESIGN:Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from???880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected. RESULTS:Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties. CONCLUSION:Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins.
| S-EPMC7252600 | biostudies-literature
Project description:We conducted a prospective cohort study with independent Discovery and Validation cohorts, to formulate predictive biomarkers for Bronchopulmonary Dysplasia in extremely preterm infants. Tracheal aspirate samples were collected at birth from extremely preterm infants. Exosomes were extracted from tracheal aspirates and total RNA was extracted from these exosomes from individual samples. miRNA profiling for all ~ 800 miRNAs was conducted on each sample by nanostring platform. This study found that a distinct airway exosomal miRNA sigrature at birth (decreased miR 876-3p) predicts future development of severe Bronchopulmonary Dysplasia in extremely preterm infants.
2017-12-29 | GSE108604 | GEO
Project description:BackgroundGrowth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term.Material/methodsInfants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age.ResultsIn total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, β = 0.90), white matter (p = 0.007, β = 0.33), cortical gray matter (p = 0.002, β = 0.43), deep gray matter (p = 0.008, β = 0.05), and cerebellar (p = 0.006, β = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors.ConclusionsEndogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants.ImpactHigh serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).
| S-EPMC9988684 | biostudies-literature
Project description:Despite significant advances in perinatal medicine, the management of extremely preterm infants in the delivery room remains a challenge. There is an increasing evidence for improved outcomes regarding the resuscitation and stabilisation of extremely preterm infants but there is a lack of evidence in the periviable (gestational age 23-25 wk) preterm subgroup. Presence of an experienced team during the delivery of extremely preterm infant to improve outcome is reviewed. Adaptation from foetal to neonatal cardiorespiratory haemodynamics is dependent on establishing an optimal functional residual capacity in the extremely preterm infants, thus enabling adequate gas exchange. There is sufficient evidence for a gentle approach to stabilisation of these fragile infants in the delivery room. Evidence for antenatal steroids especially in the periviable infants, delayed cord clamping, strategies to establish optimal functional residual capacity, importance of temperature control and oxygenation in delivery room in extremely premature infants is reviewed in this article.
| S-EPMC4857228 | biostudies-other
Project description:BACKGROUND:There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants. METHODS:We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen). RESULTS:A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups. CONCLUSIONS:The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
| S-EPMC3071534 | biostudies-literature