Concept: Amniotic fluid
Background Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spectrum of ZIKV disease in pregnancy, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses. Methods We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed the women prospectively and collected clinical and ultrasonographic data. Results A total of 88 women were enrolled from September 2015 through February 2016; of these 88 women, 72 (82%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical features included pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 28% had fever (short-term and low-grade). Women who were positive for ZIKV were more likely than those who were negative for the virus to have maculopapular rash (44% vs. 12%, P=0.02), conjunctival involvement (58% vs. 13%, P=0.002), and lymphadenopathy (40% vs. 7%, P=0.02). Fetal ultrasonography was performed in 42 ZIKV-positive women (58%) and in all ZIKV-negative women. Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses). To date, 8 of the 42 women in whom fetal ultrasonography was performed have delivered their babies, and the ultrasonographic findings have been confirmed. Conclusions Despite mild clinical symptoms, ZIKV infection during pregnancy appears to be associated with grave outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury.
BACKGROUND: Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old.Finding: fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores. CONCLUSIONS: These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.
Preterm prelabor rupture of membranes (PPROM) complicated by microbial invasion of the amniotic cavity (MIAC) leading to histological chorioamnionitis (HCA) significantly impacts perinatal morbidity. Unfortunately, no well-established tool for identifying PPROM patients threatened by these disorders is available.
Abstract Objective: To determine whether the levels of inflammatory mediators in gastric fluid (GF) of a premature newborn are associated with those in amniotic fluid (AF) of the newborn’s mother. Patients: Twenty-three pairs of pregnant women and their premature newborns <35 weeks gestation, born by Cesarean sections. Methods: Amniotic fluids and newborn gastric fluids were obtained from women during Cesarean section procedure. The mother-premature newborn dyads were retrospectively assessed to analyze the clinical and laboratory data. Concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and mannose-binding lectin (MBL) were compared between amniotic and newborn gastric fluids in each dyad. Results: Premature newborns and their mother with funisitis had significantly higher median AF IL-6 and TNF-α and GF IL-8 concentrations than those without funisitis (p = 0.022 for AF IL-6; p = 0.023 for AF TNF-α; p = 0.022 for GF IL-8). The concentrations of IL-6, IL-8, TNF-α and MBL in newborn GF were significantly correlated with those in AF in each dyad (p = 0.000, r = 0.872 for IL-6; p = 0.000, r = 0.851 for IL-8; p = 0.000, r = 0.768 for TNF-α; p = 0.000, r = 0.845 for MBL, respectively). Conclusion: The levels of inflammatory mediators in GF of a premature newborn immediately after birth are strongly associated with those in AF of the newborn's mother.
To describe the potential influence of amniotic fluid on the maternal outcome of preterm premature rupture of membranes (PROM).
Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).
Stem cells are undifferentiated cells with the capacity for differentiation. Amniotic fluid cells (AFC) have only recently emerged as a possible source of stem cells for clinical purposes. There are no ethical or sampling constraints using amniocentesis as a standard clinical procedure for obtaining an abundant supply of AFC. AFC of human origin proliferate rapidly and are multipotent with the potential for expansion in vitro to multiple cell lines. Tissue engineering technologies using AFC are being explored. AFC may be of clinical benefit for fetal therapies, degenerative disease and regenerative medicine applications. We present a comprehensive review of the evolution of human amniotic fluid cells as a possible modality for therapeutic use.
Amniotic membrane is immunologically privileged and is a reservoir of growth factors and cytokines known to modulate inflammation and enhance the healing process, while also possessing antimicrobial, antifibrosis, and antiscarring properties. These properties establish a strong argument for using amniotic membrane derived products as a treatment for burns. The purpose of this article is to describe the use of commercially available dehydrated human amnion/chorion membrane allografts in patients with partial-thickness and full-thickness burns.
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is often preceded by preterm premature rupture of the membranes (PPROM) without an identifiable cause. Pathological calcification, the deposition of hydroxyapatite (HA) in nonskeletal tissues, has been implicated in degenerative diseases including atherosclerosis and aneurism rupture. Among pathogenic mechanisms, the aberrant aggregation of HA into calciprotein particles (CPPs) and the HA-induced differentiation of mesenchymal cells into osteoblasts (ectopic osteogenesis) have been implicated. We explored the hypothesis that CPPs form in human amniotic fluid (AF), deposit in fetal membranes, and are linked mechanistically to pathogenic pathways favoring PTB. We demonstrated that fetal membranes from women with idiopathic PPROM frequently show evidence of ectopic calcification and expression of osteoblastic differentiation markers. Concentrations of fetuin-A, an endogenous inhibitor of ectopic calcification, were decreased in AF of idiopathic PPROM cases, which reflected their reduced functional capacity to inhibit calcification. Using long-term cultures of sterile AF, we demonstrated coaggregation of HA with endogenous proteins, including fetuin-A. The fetuin-HA aggregates exhibited progressive growth in vitro in a pattern similar to CPPs. When applied to amniochorion explants, AF-derived CPPs induced structural and functional pathological effects recapitulating those noted for PPROM. Our results demonstrate that disruption of protein-mineral homeostasis in AF stimulates the formation and deposition of CPPs, which may represent etiologic agents of idiopathic PPROM. Therapeutic or dietary interventions aimed at maintaining the balance between endogenous HA formation and fetuin reserve in pregnant women may therefore have a role in preventing PTB.
This study explored the association between the acute psychobiological stress response, chronic social overload and amniotic fluid corticotropin corticotropin-releasing hormone (CRH) and urocortin (UCN) in 34 healthy, second-trimester pregnant women undergoing amniocentesis. The study further examined the predictive value of second-trimester amniotic fluid CRH and UCN for fetal growth and neonatal birth outcome. The amniocentesis served as a naturalistic stressor, during which maternal state anxiety and salivary cortisol was measured repeatedly and an aliquot of amniotic fluid was collected. The pregnant women additionally completed a questionnaire on chronic social overload. Fetal growth parameters were obtained at amniocentesis using fetal ultrasound biometry and at birth from medical records. The statistical analyses revealed that the acute maternal psychobiological stress response was unassociated with the amniotic fluid peptides, but that maternal chronic overload and amniotic CRH were positively correlated. Moreover, amniotic CRH was negatively associated with fetal size at amniocentesis and positively with growth in size from amniocentesis to birth. Hardly any studies have previously explored whether acute maternal psychological stress influences fetoplacental CRH or UCN levels significantly. Our findings suggest that 1) chronic, but not acute maternal stress may affect fetoplacental CRH secretion and that 2) CRH is complexly involved in fetal growth processes as previously shown in animals.