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JAMA Dec 2023Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial... (Clinical Trial)
Clinical Trial
IMPORTANCE
Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.
OBJECTIVE
To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia.
DESIGN, SETTING, AND PARTICIPANTS
Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies.
EXPOSURE
Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age.
MAIN OUTCOMES AND MEASURES
The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement.
RESULTS
The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks).
CONCLUSIONS AND RELEVANCE
Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03101891.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Fetal Therapies; Gestational Age; Kidney; Kidney Diseases; Prospective Studies; Infusions, Parenteral; Oligohydramnios; Fetal Diseases; Lung Diseases; Isotonic Solutions; Ultrasonography, Interventional; Pregnancy Outcome; Treatment Outcome; Premature Birth
PubMed: 38051327
DOI: 10.1001/jama.2023.21153 -
Children (Basel, Switzerland) Jul 2023Information on the effect of bloody amniotic fluid during labor at term is scarce. This study assessed risk factors and adverse outcomes in labors with bloody amniotic...
Information on the effect of bloody amniotic fluid during labor at term is scarce. This study assessed risk factors and adverse outcomes in labors with bloody amniotic fluid. During the six years of this study, all nulliparas in our institution, with a trial of labor, were included. Multiple pregnancies and preterm deliveries were excluded. Outcomes were compared between the bloody amniotic fluid group and the clear amniotic fluid group. Overall, 11,252 women were included. Among them, 364 (3.2%) had bloody amniotic fluid and 10,888 (96.7%) had clear amniotic fluid. Women in the bloody amniotic fluid group were characterized by shorter duration of the second stage and higher rate of cesarean section due to non-reassuring fetal heart rate. In addition, there were higher rates of low cord pH (<7.1) and NICU admissions in the bloody amniotic fluid group. In multivariate logistic regression analysis, cesarean delivery, cord blood pH < 7.1, and NICU admission were independently associated with increased odds ratio for bloody amniotic fluid. Bloody amniotic fluid at term is associated with adverse outcomes and must be considered during labor.
PubMed: 37508705
DOI: 10.3390/children10071208 -
Respiratory Research Oct 2023Microbiome dysbiosis can have long-lasting effects on our health and induce the development of various diseases. Bronchopulmonary dysplasia (BPD) is a multifactorial... (Observational Study)
Observational Study
BACKGROUND
Microbiome dysbiosis can have long-lasting effects on our health and induce the development of various diseases. Bronchopulmonary dysplasia (BPD) is a multifactorial disease with pre- and postnatal origins including intra-amniotic infection as main risk factor. Recently, postnatal pathologic lung microbiota colonization was associated with BPD. The objectives of this prospective observational cohort study were to describe differences in bacterial signatures in the amniotic fluid (AF) of intact pregnancies without clinical signs or risk of preterm delivery and AF samples obtained during preterm deliveries and their variations between different BPD disease severity stages.
METHODS
AF samples were collected under sterile conditions during fetal intervention from intact pregnancies (n = 17) or immediately before preterm delivery < 32 weeks (n = 126). Metabarcoding based approaches were used for the molecular assessment of bacterial 16S rRNA genes to describe bacterial community structure.
RESULTS
The absolute amount of 16S rRNA genes was significantly increased in AF of preterm deliveries and detailed profiling revealed a reduced alpha diversity and a significant change in beta diversity with a reduced relative abundance of 16S rRNA genes indicative for Lactobacillus and Acetobacter while Fusobacterium, Pseudomonas, Ureaplasma and Staphylococcus 16S rRNA gene prevailed. Although classification of BPD by disease severity revealed equivalent absolute 16S rRNA gene abundance and alpha and beta diversity in no, mild and moderate/severe BPD groups, for some 16S rRNA genes differences were observed in AF samples. Bacterial signatures of infants with moderate/severe BPD showed predominance of 16S rRNA genes belonging to the Escherichia-Shigella cluster while Ureaplasma and Enterococcus species were enriched in AF samples of infants with mild BPD.
CONCLUSIONS
Our study identified distinct and diverse intrauterine 16S rRNA gene patterns in preterm infants immediately before birth, differing from the 16S rRNA gene signature of intact pregnancies. The distinct 16S rRNA gene signatures at birth derive from bacteria with varying pathogenicity to the immature lung and are suited to identify preterm infants at risk. Our results emphasize the prenatal impact to the origins of BPD.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Infant, Premature; Bronchopulmonary Dysplasia; Amniotic Fluid; RNA, Ribosomal, 16S; Prospective Studies; Bacteria
PubMed: 37845700
DOI: 10.1186/s12931-023-02560-w -
The Science of the Total Environment Oct 2023The present paper provides the first integrative assessment of the capacity of naringin and its metabolite, naringenin, to induce hormetic dose responses within a broad... (Review)
Review
The present paper provides the first integrative assessment of the capacity of naringin and its metabolite, naringenin, to induce hormetic dose responses within a broad range of experimental biomedical models. The findings indicate that these agents commonly induced protective effects that are typically mediated via hormetic mechanisms leading to biphasic dose-response relationships. The maximum protective effects are generally modest, 30-60 % greater than control group values. The range of experimental findings with these agents has been reported for models with various neurodegenerative diseases, nucleus pulpous cells (NPCs) located within intravertebral discs, several types of stem cells (i.e., bone marrow, amniotic fluid, periodontal, endothelial) as well as cardiac cells. These agents also were effective within preconditioning protocols protecting against environmental toxins such as ultraviolet radiation (UV), cadmium, and paraquat. The mechanism(s) by which the hormetic responses mediates these biphasic dose responses is complex but commonly involves the activation of nuclear factor erythroid 2-related factor (Nrf2), an increasingly recognized regulator of cellular resistance to oxidants. Nrf2 appears to play a role in controlling the basal and induced expression of an array of antioxidant response element-dependent genes to regulate oxidant exposure's physiological and pathophysiological outcomes. Hence its importance in the assessment of toxicologic and adaptive potential is likely to be significant.
Topics: Hormesis; NF-E2-Related Factor 2; Ultraviolet Rays; Heart
PubMed: 37295528
DOI: 10.1016/j.scitotenv.2023.164728 -
Acta Obstetricia Et Gynecologica... Aug 2023Our objective was to study the strength of the association between meconium-stained amniotic fluid and severe morbidity among neonates of nulliparas with prolonged... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Our objective was to study the strength of the association between meconium-stained amniotic fluid and severe morbidity among neonates of nulliparas with prolonged pregnancies.
MATERIAL AND METHODS
This was a secondary analysis of the NOCETER randomized trial that took place between 2009 and 2012 in which 11 French maternity units included 1373 nulliparas at 41 weeks of gestation onwards with a single live fetus in cephalic presentation. This analysis excluded patients with a cesarean delivery before labor and those with bloody amniotic fluid or of unreported consistency. The principal end point was a composite criterion of severe neonatal morbidity (neonatal death, 5-minute Apgar <7, convulsions in the first 24 h, meconium aspiration syndrome, mechanical ventilation ≥24 h, or neonatal intensive care unit admission for 5 days or more). The neonatal outcomes of pregnancies with thin or thick meconium-stained amniotic fluid were compared with those with normal amniotic fluid. The association between the consistency of the amniotic fluid and neonatal morbidity was tested by univariate and then multivariate analysis adjusted for gestational age at birth, duration of labor, and country of birth.
RESULTS
This study included 1274 patients: 803 (63%) in the group with normal amniotic fluid, 196 (15.4%) in the thin amniotic fluid group, and 275 (21.6%) in the thick amniotic fluid group. The neonates of patients with thick amniotic fluid had higher rates of neonatal morbidity than those of patients with normal amniotic fluid (7.3% vs. 2.2%; p < 0.001; adjusted relative risk [aRR] 3.3, 95% confidence interval [CI] 1.7-6.3), but those of patients with thin amniotic fluid did not (3.1% vs. 2.2%; p = 0.50; aRR 1.0, 95% CI, 0.4-2.7).
CONCLUSIONS
Among nulliparas at 41 weeks onwards, only thick meconium-stained amniotic fluid is associated with a higher rate of severe neonatal morbidity.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Infant, Newborn, Diseases; Meconium; Meconium Aspiration Syndrome; Obstetric Labor Complications; Pregnancy Complications; Pregnancy, Prolonged
PubMed: 37377254
DOI: 10.1111/aogs.14619