What is the Impact of Abnormal Amniotic Fluid Volumes on Perinatal Outcomes in Normal Compared with At-Risk Pregnancies?

OBJECTIVE: Assessing amniotic fluid volume is an integral part of obstetric practice. Data are sparse on at-risk pregnancy and amniotic fluid volumes. The aim of our study was to determine if there is a difference in perinatal outcomes based on complications of pregnancy and amniotic fluid volumes. We hypothesized that at-risk pregnancies with abnormal amniotic fluid volumes would have worse perinatal outcomes than normal pregnancies with abnormal amniotic fluid volumes. STUDY DESIGN: This retrospective cohort study evaluated both normal and at-risk singleton pregnancies with intact membranes on admission for delivery. Amniotic fluid volumes were estimated using both the amniotic fluid index (AFI) and single deepest pocket (SDP) techniques. All sonograms were performed by trained ultrasound technicians or obstetrician/gynecologists. We placed 3365 women into 6 separate groups (at-risk versus normal, then further stratified by oligohydramnios by SDP, normal fluid, or polyhydramnios by AFI). RESULTS: At-risk pregnancies with normal fluid and at-risk pregnancies with polyhydramnios have significantly increased risk of neonatal intensive care unit (NICU) admission [OR 2.06 (95% CI 1.63,2.60), OR 2.74 (95% CI 1.54, 4.87)]. Birthweight is significantly higher in at-risk and normal pregnancies with polyhydramnios than those with normal pregnancies and normal fluid (p<0.0001). Birthweight is significantly lower in at-risk pregnancies with oligohydramnios (p<0.0001). There were no significant differences in need for amnioinfusion in labor, variables or lates influencing delivery, meconium staining, or umbilical artery pH <7.1. CONCLUSION: Our study attempted to further define risk of adverse pregnancy outcomes by defining the pregnancy as normal or at-risk and amniotic fluid volumes. Contrary to our hypothesis, we did not find an increased risk of many of the adverse perinatal outcomes we studied amongst at-risk pregnancies with abnormal fluid. There was an increased risk of NICU admission associated with polyhydramnios in normal and at-risk pregnancies.

Correction: The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor.

Prematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO4) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO4/BMTZ mitigated the neuroinflammatory process in wt but not Nr4a1 KO brains. These results correspond with a reduction in cerebral hemorrhage in wt but not mutant embryos from dams given MgSO4/BMTZ. Further analysis with Nr4a1-GFP-Cre × tdTomato loxP reporter mice revealed that the upregulation of Nr4a1 with perinatal neuroinflammation occurs in the cerebral vasculature. Altogether, this study implicates Nr4a1 in the developing vasculature as a potent mediator of neuroinflammatory brain injury that occurs with preterm birth. It is also possible that MgSO4/BMTZ mitigates this process by direct or indirect inhibition of Nr4a1.

Perinatal Pyogenic Liver Abscess: A Rare Entity and First Reported Case of Klebsiella pneumoniae.

Introduction Pyogenic liver abscess (PLA) is a rare clinical entity, occurring in ∼2.3 per 100,000 patients. Perinatal PLA syndromes are exceedingly rare with just seven previously described cases in the literature and no prior Klebsiella-associated reports. Case A 29-year-old gravida 2 para 1 woman at 11 weeks gestation reporting fever, body aches, and headache. Search for an infectious source identified a 4-cm liver abscess. Percutaneous drainage confirmed Klebsiella pneumoniae infection. The patient was treated with antibiotics until imaging verified complete resolution of the abscess. Conclusion PLA is an uncommon etiology of sepsis in pregnancy. A thorough workup until a source was identified resulted in accurate diagnosis. This allowed for directed therapy and prompt recovery, undoubtedly contributing to favorable pregnancy outcomes in this first report of Klebsiella-associated perinatal PLA.

Evaluating maternal hyperglycemic exposure and fetal placental arterial dysfunction in a dual cotyledon, dual perfusion model.

BACKGROUND: Gestational diabetes affects almost 1 in 10 pregnancies and is associated with adverse outcomes including fetal demise. Pregnancy complications related to diabetes are attributed to placental vascular dysfunction. With diabetes, maternal hyperglycemia is thought to promote placental vasoconstriction. However, it remains poorly understood if and how hyperglycemia leads to placental vascular dysfunction or if humoral factors related to maternal diabetes are responsible. METHODS AND RESULTS: Utilizing a human placenta dual cotyledon, dual perfusion assay we examined the arterial pressure response to the thromboxane mimetic U44619, in cotyledons exposed to normal vs. a hyperglycemic infusion into the intervillous space. Tissues were then analyzed for the activity of key signaling molecules related to vascular tone; eNOS, Akt, PKA and VEGFR2. Results indicate a significant increase in fetal vascular resistance with maternal exposure to hyperglycemia. This response corresponded with a reduction in the phosphorylation of eNOS at Ser1177 and Akt at Thr308. In contrast, VEGFR2 at Tyr1175 and PKA at Thr197 were not different with hyperglycemia. CONCLUSION: Reductions of eNOS and Akt phosphorylation at key residues implicated in nitric oxide production suggest that hyperglycemia alters the vasodilatory signaling of placental vessels. In contrast, acute hyperglycemic exposure may not alter vasoconstriction via VEGF and PKA signaling. Altogether our results link hyperglycemic exposure in human placentas to nitric oxide signaling; a mechanisms that may account for the elevations in vascular resistance commonly observed in diabetic pregnancies.

Evaluation of Sildenafil and Tadalafil for Reversing Constriction of Fetal Arteries in a Human Placenta Perfusion Model.

Fetal growth restriction resulting from reduced placental blood perfusion is a major cause of neonatal morbidity and mortality. Aside from intense surveillance and early delivery, there is no treatment for fetal growth restriction. A potential treatment associated with placental vasoconstriction is the class of PDE5 (phosphodiesterase type 5) inhibitors such as sildenafil, which is known to cross the placenta. In contrast, tadalafil, a more potent and selective PDE5 inhibitor has not been studied in pregnancy or experimental models of fetal growth restriction. Therefore, we compared the efficacy of these 2 PDE5 inhibitors for reversing vasoconstriction in an ex vivo human placental model and evaluating molecular and physiological responses. Sildenafil and tadalafil were infused into the intervillous space in a preconstricted human placental dual cotyledon, dual perfusion assay for the comparison of arteriole pressures and molecular indicators of drug inhibition. Results indicate a decrease arterial pressure with sildenafil citrate compared with controls, whereas tadalafil showed no difference. PDE5 and endothelial nitric oxide synthase activity were altered with sildenafil but not tadalafil. Sildenafil citrate improved preconstricted placental arterial perfusion in a human placental model, whereas tadalafil showed no response. It is possible that tadalafil did not cross the human placental barrier or was degraded by trophoblasts. This study supports human clinical trials exploring sildenafil as a potential treatment for improving fetal blood flow in fetal growth restriction associated with vasoconstriction.

Long-term impact of intrauterine neuroinflammation and treatment with magnesium sulphate and betamethasone: Sex-specific differences in a preterm labor murine model.

Preterm infants are at significantly increased risk for lifelong neurodevelopmental disability with male offspring disproportionately affected. Corticosteroids (such as betamethasone) and magnesium sulphate (MgSO4) are administered to women in preterm labor to reduce neurologic morbidity. Despite widespread use of MgSO4 in clinical practice, its effects on adult offspring are not well known nor have sex-specific differences in therapeutic response been explored. The objective of our study was to examine the long-term effects of perinatal neuroinflammation and the effectiveness of prenatal MgSO4/betamethasone treatments between males and females in a murine model via histologic and expression analyses. Our results demonstrate that male but not female offspring exposed to intrauterine inflammation demonstrated impaired performance in neurodevelopmental testing in early life assessed via negative geotaxis, while those exposed to injury plus treatment fared better. Histologic analysis of adult male brains identified a significant reduction in hippocampal neural density in the injured group compared to controls. Evaluation of key neural markers via qRT-PCR demonstrated more profound differences in gene expression in adult males exposed to injury and treatment compared to female offspring, which largely showed resistance to injury. Prenatal treatment with MgSO4/betamethasone confers long-term benefits beyond cerebral palsy prevention with sex-specific differences in response.

Actinomyces in Pregnancy: A Review of the Literature.

IMPORTANCE: Actinomyces is commonly found in many areas of the body where it derives a benefit without harming the host. When it does infect the host during pregnancy, is that infection a threat to the obstetric patient and does that infection cause adverse pregnancy outcomes? OBJECTIVE: The aim of this study was to review what is known about Actinomyces infections and the impact of an Actinomyces infection on pregnancy outcomes. EVIDENCE ACQUISITION: A PubMed search was undertaken with the search years unlimited to April 1, 2016, and restricted to articles in English. The search terms included "actinomyces," "pregnancy," "prenatal," "maternal," "actinomyces infection," "pregnancy," "chorioamnionitis," "preterm labor," "premature birth," or "postpartum actinomyces." RESULTS: Eighteen of the 154 identified articles are the basis of this review. Actinomyces is a rod-like positive bacterium. The diagnosis of an Actinomyces infection can be by culture or Gram stain. Actinomyces is commensal and typically only infects after a mucosal break or lesion. Seventeen cases were identified in pregnancy. Ten cases were complicated by chorioamnionitis and a preterm delivery. A nidus leading to infection was identified in 12 of the cases including women with a cervical cerclage, dental abscesses, appendicitis, renal actinomycosis, and ovarian abscesses. Adverse pregnancy outcomes have been linked with periodontal disease, but treatment did not prevent preterm delivery in a randomized, blinded, controlled trial. CONCLUSIONS: Actinomyces infections in pregnancy are rare but, if they occur, have been linked primarily with preterm deliveries. TARGET AUDIENCE: Obstetricians and gynecologists, family physicians. LEARNING OBJECTIVES: After completing this activity, the learner should be better able to identify the areas of the body where Actinomyces infections occur and how the infections typically occur, identify the pathophysiologic changes that occur during pregnancy that might lead to an Actinomyces infection and how that infection may affect pregnancy outcomes, and describe the treatment for mild and severe Actinomyces infections.