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Objective: To compare the effectiveness and outcomes of interventional resealing of membranes, "amniopatch" for spontaneous vs. iatrogenic preterm premature rupture of the membranes (sPPROM and iPPROM)., Methods: We performed a systematic review of literature involving an electronic search of the following databases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Scopus. An indirect meta-analysis was then performed to compare the obstetric, maternal, fetal, and neonatal outcomes of amniopatch between the sPPROM and iPPROM groups., Results: The mean gestational age (GA) at the time rupture was 17.8 ± 1.8 and 25.2 ± 3.8 weeks for iPPROM and sPPROM, respectively, p  = .005. Mean GA at the time of amniopatch procedure was 19.2 ± 2.07 weeks for iPPROM and 23 ± 3.1 weeks of gestation for sPPROM, p  = .023. The rates of fluid re-accumulation (sPPROM 26% and iPPROM 53%, p  = .09) were comparable between the sPPROM and iPPROM groups. Neonatal outcomes except for the rate of IUFD were also comparable between the groups. The incidence of IUFD was significantly higher in the iPPROM group (ES: 24%; 95% CI: 8.00-44.0%; p  < .001), compared to sPPROM (ES: 0%; 95% CI: 0.00-4.00%). Obstetric and maternal outcomes were comparable between the two groups., Conclusions: Amniopatch appears to be a feasible and safe procedure for PPROM treatment. Further research is warranted to investigate the effectiveness of this procedure and establish a standardized criterion for the appropriate selection of patients that could benefit from this intervention.

The COVID-19 pandemic represents the greatest challenge to date faced by the medical community in the 21st century. The rate of rapid dissemination, magnitude of viral contagiousness, person to person transmission at an asymptomatic phase of illness pose a unique and dangerous challenge for all patients, including neonatal and obstetric patients. Although scientific understanding of the pathophysiology of the disease, nature of transmission, and efficacy of mitigation strategies is growing, neither a cure or vaccine have been developed. While COVID-19 is primarily a disease of older patients, infection is now seen across all age demographics with reports of illness in pregnant patients and infants. Altered hormone status and predominance of Th-2 immune helper cells may result in increased predisposition to SARS-CoV-2. Case reports of pregnant patients demonstrate a clinical presentation comparable to non-pregnant adults, but evidence of vertical transmission to the fetus is controversial. Neonatal reports demonstrate an inconsistent and non-specific phenotype, and it is often difficult to separate COVID-19 from the underlying conditions of prematurity or bacterial infection. The development of international registries to enable risk profiling of COVID-19 positive pregnant mothers and/or their offspring may facilitate the development of enhanced mitigation strategies, medical treatments and effective vaccinations.

Interleukin-1 beta (IL-1β) is a cytokine mediator of perinatal brain injury. The effect of sub-chronic systemic IL-1β exposure in perinatal and offspring outcomes is unclear. The aim of this study was to examine the effects of maternal IL-1β exposure on pregnancy and offspring outcomes. At E15, CD1 dams were allocated to receive intraperitoneal injection of phosphate buffered saline or mouse recombinant IL-1β (1 mcg) for four consecutive days. We analyzed pup survivaland neurobehavioral status. At E18, placental H&E staining and fetal brain Nissl staining was performed. Placental gene expression was analyzed by qPCR and T cell infiltration was analyzed by flow cytometry. Effects of inflammation on feto-placental blood flow were analyzed by Doppler ultrasonography. IL-1β decreased pup survival (P < .0001) and adversely affected offspring performance on neurodevelopmental tests (P < .05). Placentas of exposed dams exhibited significant thinning of maternal and fetal sides, and fetal brain exhibited cortical thinning. Placental qPCR analysis revealed significant upregulation of NFκB2 (P = .0021) and CXCL11 (P = .0401). While maternal IL-1β exposure did not affect feto-placental blood flow, placental flow cytometry showed an increase in placental infiltration of CD4 + T cells at 24 h post-injection (hpi, P < .0001) and CD8 + T cells at 72 hpi (P = .0217). Maternal sub-chronic, systemic inflammation with IL-1β decreased pup survival and played a key role in perinatal brain injury. The mechanisms behind these outcomes may involve immune system activation and alterations in placental T cell trafficking., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several facets of immune activation and neuronal function through its importance in interleukin (IL)-1β secretion. We hypothesized that blockade of P2X7 would prevent perinatal brain injury associated with exposure to intrauterine (IU) inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7 receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). Furthermore, we utilized embryo transfer experiments to delineate whether the P2X7 was the key mediator of IU inflammation-associated brain injury on maternal or fetal sides. In these experiments, P2X7-/- dams were embryo-transferred wild type embryos and wild type dams were embryo-transferred P2X7-/- embryos. In the mouse model of intrauterine inflammation, pharmacologic blockade of P2X7R reduced preterm birth rate, improved offspring performance on neuromotor tests as well as the dendritic arborization and density of cortical neurons. Embryo transfer experiments demonstrated the importance of maternal P2X7R in IU inflammation-mediated effects on offspring. Both genetic and pharmacologic blockade of IL-1β signaling, by targeting maternal P2X7R, ameliorated perinatal brain injury following exposure to IU inflammation. Specific targeting of maternal P2X7R may provide a clinically useful tool to prevent both preterm birth and prematurity-associated perinatal brain injury, and further studies are urgently needed., (© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While the origins of syphilis remain unknown, it has long been recognized as an infectious entity with complex pathophysiology. In this review, we highlighted the epidemiology and risk factors associated with syphilis. The incidence of syphilis in most populations showed a consistent upward trend until the 1940s with the introduction of penicillin as the preferred treatment. The emergence of congenital syphilis and vertical transmission has been a direct result of heterosexual syphilis transmission. We also explore the microbiology and pathogenesis of Treponema pallidum as it directly correlates with its route of transmission and infectivity. The clinical features are best categorized into stages (primary, secondary, early, and late latent and tertiary). The primary stage presents as a characteristic chancre and inguinal adenopathy, while the secondary "bacteremia" stage has a predilection to dermatologic manifestations and constitutional symptoms. The latent phase of syphilis witnesses a quiescent period with variable relapse of symptoms and finally, one-third of untreated patients undergo tertiary syphilis years after the initial infection characterized by severe neurologic or cardiovascular symptomatology. We will also review the data collected for congenital syphilis from the CDC as this can manifest with stillbirth, neonatal death, and nonimmune hydrops. The diagnosis of syphilis focuses on a combination of nontreponemal and treponemal antibody tests with the CDC recommending a traditional algorithm from screening to confirmation. However, other agencies have recently adopted the reverse testing algorithm which has outperformed the traditional algorithm in certain populations. We finally focus on syphilotherapy and monitoring response to treatment with a specific emphasis on pregnancy. Birth Defects Research 109:347-352, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: The development of periventricular white matter injury (PWMI) in the preterm neonate is the most common insult portending neurologic impairment and is linked with the later development of cerebral palsy. The pathogenesis of PWMI targets premyelinating oligodendrocytes of the periventricular region secondary to free radicals, cytokine toxicity, and excitatory neurotransmitters. The primitive nature of the vasculature in the developing fetal cortex lends to its predilection to PWMI and cerebral ischemia with less arterial anastomoses at arterial border zones and failure to compensate for global hypotension, termed the "pressure-passive" circulation., Objective: Our objective is to determine the relative risk (RR) of fetal metabolic acidosis and perinatal infection in the development of PWMI in very low birthweight (VLBW) (<1500 g) neonates., Study Design: This is a cohort study of all VLBW neonates admitted to our neonatal intensive care unit from April 2009 through December 2014, comparing those who developed PWMI on neonatal head ultrasound at 6 weeks of life to those who did not. Neonates with chromosomal or major congenital abnormalities were excluded. Generalized linear modeling, adjusting for variables significantly different on bivariate analysis, was conducted., Results: During this 5-year and 8-month period there were 374 VLBW neonates admitted; 35 (9.4%) had PWMI. VLBW neonates without PWMI were significantly more likely to have intrauterine growth restriction (2.9% PWMI, 21.5% no PWMI; P = .006), while those neonates with PWMI had a significantly lower gestational age (26.3 ± 2.2 vs 28.0 ± 2.5 weeks; P < .001) and birthweight (868 ± 237 vs 993 ± 276 g; P = .009). There was no significant difference in umbilical arterial pH (7.25 ± 0.15 vs 7.27 ± 0.09; P = .34), base deficit (4.6 ± 6.0 vs 3.4 ± 3.3 mmol/L; P = .11), or pH <7.0 or base deficit >12 mmol/L at birth (10.7% vs 3.2%; P = .09). On bivariate analysis neonates with PWMI had a significant increase in positive cerebrospinal fluid (CSF) cultures (22.9% vs 1.5%; P < .001). The initial lumbar puncture was performed at a similar day of life, and neonates with PWMI had significantly elevated CSF white blood cell counts (5%, 50%, and 95%; 16, 175, and 709/mm(3); 1, 3, and 27/mm(3); P = .008). Generalized linear modeling, adjusted for gestational age and the presence of intrauterine growth restriction, showed that fetal metabolic acidosis had RR 2.59 (95% confidence interval, 1.14-5.92; P = .02) and neonatal CSF infection had RR 4.94 (95% confidence interval, 2.4-10.3; P < .001) for association with PWMI., Conclusion: The RR of neonatal CSF infection being associated with PWMI was 2-fold greater than metabolic acidosis at the time of birth. Decreasing the incidence of CSF infections would have a greater impact on preventing PWMI, a precursor of cerebral palsy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The study of preterm labor and prematurity has undergone a major transformation in its approach from an inevitable part of obstetrics with few answers to one in which science has led to knowledge and clinical intervention. Despite these advancements, understanding of preterm labor and prevention of prematurity is still limited. In the current review, we begin the discussion with fetal viability, first from a historical perspective and then from the understanding of this issue from a prospective of various professional organizations. We then present the scope of the problem of preterm birth from various countries including the discrepancy between the US and Europe. We continue with updates on extreme prematurity and outcomes with two longitudinal studies from the past 2 years. We further review available interventions for prematurity and discuss the use of antenatal corticosteroids. First, we examine their use in the context of professional recommendations and then examine the trajectory of their continued use in the late preterm period. We focus on a European-based trial with preliminary results and an ongoing American counterpart. The current knowledge of molecular mechanisms behind preterm labor is presented with a focus on the multiple etiologies of preterm labor, both known and presumed, with updates in the basic science realm. Furthermore, we present up-to-date studies on prediction of preterm birth and prematurity-related morbidity.