Doppler and birth weight Z score: predictors for adverse neonatal outcome in severe fetal compromise

BACKGROUND: An adequate placental perfusion is crucial for the normal growth and well being of the fetus and newborn. The blood flow through the placenta can be compromised in a variety of clinical situations, always causing important damage to the gestation. Our objective is to identify significant predictors for adverse neonatal outcome in severe fetal compromise. METHODS: Consecutive premature fetuses at between 25 and 32 weeks with severe placental insufficiency were examined prospectively. Inclusion criteria were: (i) singletons (ii) normal anatomy; (iii) abnormal umbilical artery Doppler pulsatility index (PI); (iv) abnormal cerebroplacental ratio; (v) middle cerebral artery (MCA) PI < - 2SD ("brain sparing"); (vi) last Doppler examination performed within 24 hours prior to delivery. All 46 patients that met criteria and started the study were followed to the end. We considered as independent potential predicting variables: absent or reversed end diastolic flow in umbilical artery, abnormal ductus venosus S/A ratio, absent or reversed flow during atrial contraction in the ductus venosus and birth weight Z score. Outcome parameters were: neonatal mortality and severe neonatal morbidity. RESULTS: Backward stepwise logistic regression analysis was used to determine the optimal model for the prediction of neonatal mortality and severe neonatal morbidity. In this analysis birth weight Z score index showed the strongest association OR = 1,87 [1,17-2,99] with all neonatal outcome, all other independent variables were excluded for the optimal model. There was no mortality for the group with normal birth weight Z score. CONCLUSION: Our study suggests that birth weight Z score is the strongest predictor of adverse neonatal outcome in severe placental insufficiencies. Such use of Z scores, allowing to get rid of gestational age or sex covariates could be extended to estimated fetal weight and might help in making important decisions in the management of compromised pregnancies

Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome

Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research.Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls.Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis.Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

Contains fulltext : 65628.pdf ( ) (Open Access)BACKGROUND: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. METHODS/DESIGN: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. DISCUSSION: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. TRIAL REGISTRATION: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217

Utility of fetal echocardiogram in high-risk patients

AimPatients at high risk of fetal congenital heart disease are commonly referred for second trimester fetal echocardiogram. The objective of this study was to evaluate the utility of routine fetal echocardiogram in high-risk patients after the evaluation of the four-chamber/left ventricular outflow tract (LVOT) views during comprehensive second trimester anatomy ultrasound.MethodsSecond trimester comprehensive anatomy ultrasounds, which included a four-chamber/LVOT view, and subsequent fetal echocardiograms carried out at the Duke University Medical Center from January 1995 and July 2002 were reviewed. Those fetal echocardiograms carried out between 17 and 30 weeks gestation were included in the analysis.ResultsA total of 725 individual subjects met the inclusion criteria. Twenty-nine fetal echocardiograms were ultimately reported as abnormal. Of these, 19 had an abnormal four-chamber/LVOT view, four had a suboptimal view and six had a normal view. Of the six patients with a normal four-chamber/LVOT, all had been referred for echocardiogram based on the presence of other significant fetal anomalies noted at the time of second trimester anatomy ultrasound (3), documented aneuploidy (2), and significant fetal arrhythmia (1).ConclusionUtility in carrying out fetal echocardiogram was seen in patients with an abnormal four-chamber/LVOT view, a suboptimal view in a high-risk patient, and the presence of other significant fetal abnormalities. Utility was not seen in patients with pre-existing diabetes mellitus.Muller, Peter R. ; James, Andra ; Feldman, Kristin ; Herlong, J. Ren

Serum metabolomic markers for traumatic brain injury: a mouse model

Introduction Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.Objectives Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.Methods A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.Results Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.Conclusion Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.</div