Vaginal-perianal or vaginal-perineal compared with vaginal-rectal culture-based screening for Group B Streptococci (GBS) colonization during the third trimester of pregnancy: a systematic review and meta-analysis.

BACKGROUND: Screening for maternal anogenital Group B streptococci (GBS) colonization in pregnancy with initiation of intravenous intrapartum antibiotic prophylaxis as indicated has led to a significant reduction in the incidence of neonatal GBS infection. This study aims to evaluate the agreement between vaginal-perianal or vaginal-perineal culture and the more typically used vaginal-rectal culture for screening for maternal anogenital GBS colonization in the third trimester of pregnancy. METHODS: Eligible English-language studies published until January 2020 were retrieved from Scopus, Web of Science, PubMed, Embase, and ClinicalTrials.gov databases. Studies were compiled that assessed for GBS colonization utilizing vaginal-perianal or vaginal-perineal culture and vaginal-rectal culture during the third trimester of pregnancy. Nonoriginal research articles and studies that did not assess pregnant patients, did not use culture-based screening, or did not compare vaginal-perianal or vaginal-perineal culture with vaginal-rectal culture were excluded. The search identified 559 articles with three prospective cohort studies that met inclusion criteria, including 643 participants. Quality was assessed using the Newcastle-Ottawa Scale, and risk of bias was assessed using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Patient characteristics and associated pain with specimen collection were abstracted. Meta-analyses of both the raw agreement and the Cohen's kappa statistic were performed. RESULTS: Within the three included studies, the range of GBS detection was 17.6-34.0%, consistent with the anticipated prevalence of GBS colonization reported in earlier publications. For both raw agreement and Cohen's kappa coefficient, the test for heterogeneity was not significant, indicating low heterogeneity among studies. The pooled estimate of the raw agreement was 0.97 (95%CI 0.95-0.98) and of the Cohen's kappa coefficient was 0.91 (95% CI: 0.87-0.95), indicating (according to the Landis and Koch criteria) an "almost perfect" agreement between the compared clinical tests. In the two studies that assessed procedure-related patient discomfort, vaginal-rectal swabbing caused more discomfort. CONCLUSION: Use of vaginal-perineal culture for assessment of maternal GBS colonization is comparable to the more typically utilized vaginal-rectal culture and is associated with less discomfort.

Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons.

Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While Aedes species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia; therefore, we also compared the French Polynesian (FP) ZIKV isolate to the Puerto Rican (PR) isolate. Timed-pregnant baboons (n = 6) were inoculated via vaginal deposition of baboon semen containing 106 focus-forming units (FFU) of ZIKV (n = 3 for FP isolate H/PF/2013; n = 3 for PR isolate PRVABC59) at midgestation (86 to 95 days of gestation [dG]; term, 183 dG) on day 0 (all dams) and then at 7-day intervals through 3 weeks. Maternal blood, saliva, and cervicovaginal wash (CVW) samples were obtained. Animals were euthanized at 28 days (n = 5) or 39 days (n = 1) after the initial inoculation, and maternal/fetal tissues were collected. Viremia was achieved in 3/3 FP ZIKV-infected dams and 2/3 PR ZIKV-infected dams. ZIKV RNA was detected in CVW samples of 5/6 dams. ZIKV RNA was detected in lymph nodes but not the ovaries, uterus, cervix, or vagina in FP isolate-infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3), and vagina (2/3) in PR isolate-infected dams. Placenta, amniotic fluid, and fetal tissues were ZIKV RNA negative in the FP isolate-infected dams, whereas 2/3 PR isolate-infected dam placentas were ZIKV RNA positive. We conclude that ZIKV-infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of widespread dissemination to tissues, including reproductive tissues and placenta, than the FP isolate.IMPORTANCE Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon.

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5-7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

Insulin Dosing, Glycemic Control, and Perinatal Outcomes in Pregnancies Complicated by Type-2 Diabetes.

OBJECTIVE: This study aimed to evaluate the prevalence of severe insulin resistance (insulin requirements ≥2 units/kg) at delivery and the relationship between severe insulin resistance, glycemic control, and adverse perinatal outcomes in pregnant women with type-2 diabetes mellitus. STUDY DESIGN: This is a retrospective cohort study of women with type-2 diabetes mellitus who delivered between January 2015 and December 2017 at a tertiary academic medical center. Maternal demographic information, self-monitored blood sugars, and insulin doses were abstracted from the medical record. Multivariable logistic regression was used to identify maternal baseline characteristics associated with severe insulin resistance at delivery. RESULTS: Overall 72/160 (45%) of women had severe insulin resistance. Women in the severe insulin resistance group demonstrated evidence of suboptimal glycemic control as evidenced by higher mean hemoglobin A1c (HbA1c) values (7.2 [ ± 1.1] vs. 6.6 [ ± 1.3%], p = 0.003), higher mean fasting (104.0 [ ± 17.4] vs. 95.2 [ ± 11.7 mg/dL], p < 0.001) and postprandial glucose values (132.4 [ ± 17.2] vs. 121.9 [ ± 16.9 mg/dL]), p < 0.001), and a higher percentage of total glucose values that were elevated above targets (37.7 [95% confidence interval (CI): 26.8-50] vs. 25.6 [95% CI: 13.3-41.3%], p < 0.001). Maternal HbA1c ≥6.5% and insulin use prior to pregnancy were associated with a higher prevalence of severe insulin resistance, while Hispanic ethnicity and non-White race were associated with a lower prevalence of severe insulin resistance. The rates of adverse perinatal outcomes including large for gestational age (LGA) birth weight, cesarean delivery, and hypertensive disorders of pregnancy did not differ between groups. CONCLUSION: Severe insulin resistance is common among pregnant women with type-2 diabetes, and it is associated with suboptimal glycemic control. Future studies are necessary to develop strategies to identify women with severe insulin resistance early in pregnancy and facilitate adequate insulin dosing. KEY POINTS: · Severe insulin resistance is common.. · BMI does not predict severe insulin resistance.. · Suboptimal glycemic control is common..

Translational Model of Zika Virus Disease in Baboons.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus with devastating outcomes seen recently in the Americas due to the association of maternal ZIKV infection with fetal microcephaly and other fetal malformations not previously associated with flavivirus infections. Here, we have developed the olive baboon (Papio anubis) as a nonhuman primate (NHP) translational model for the study of ZIKV pathogenesis and associated disease outcomes to contrast and compare with humans and other major NHPs, such as macaques. Following subcutaneous inoculation of adult male and nonpregnant female baboons, viremia was detected at 3 and 4 days postinfection (dpi) with the concordant presentation of a visible rash and conjunctivitis, similar to human ZIKV infection. Furthermore, virus was detected in the mucosa and cerebrospinal fluid. A robust ZIKV-specific IgM and IgG antibody response was also observed in all the animals. These data show striking similarity between humans and the olive baboon following infection with ZIKV, suggesting our model is a suitable translational NHP model to study ZIKV pathogenesis and potential therapeutics.IMPORTANCE ZIKV was first identified in 1947 in a sentinel rhesus monkey in Uganda and subsequently spread to Southeast Asia. Until 2007, only a small number of cases were reported, and ZIKV infection was relatively minor until the South Pacific and Brazilian outbreaks, where more severe outcomes were reported. Here, we present the baboon as a nonhuman primate model for contrast and comparison with other published animal models of ZIKV, such as the mouse and macaque species. Baboons breed year round and are not currently a primary nonhuman primate species used in biomedical research, making them more readily available for studies other than human immunodeficiency virus studies, which many macaque species are designated for. This, taken together with the similarities baboons have with humans, such as immunology, reproduction, genetics, and size, makes the baboon an attractive NHP model for ZIKV studies in comparison to other nonhuman primates.

Prophylaxis Against Early-onset Group B Streptococcus Infections in Pregnant Women Who Are Allergic to Penicillin.

Group B Streptococcus (GBS) infection remains a significant cause of neonatal morbidity and mortality. Adoption of screening for maternal genital tract colonization and intrapartum antibiotic prophylaxis has significantly reduced early-onset neonatal GBS infections. For women with an allergy to penicillin, recommended agents for prophylaxis have been well-outlined, but compliance with guideline recommendations is poor. There have been ongoing efforts in vaccine development, but no vaccination currently is available for either preconception or antenatal administration. This article will review established screening techniques, intrapartum antibiotic prophylactic regimens, and management specifically of the penicillin-allergic pregnant woman who is colonized with GBS.

Impact of dietary aromatic amino acids on osteoclastic activity.

We had shown that aromatic amino acid (phenylalanine, tyrosine, and tryptophan) supplementation prevented bone loss in an aging C57BL/6 mice model. In vivo results from the markers of bone breakdown suggested an inhibition of osteoclastic activity or differentiation. To assess osteoclastic differentiation, we examined the effects of aromatic amino acids on early /structural markers as vitronectin receptor, calcitonin receptor, and carbonic anhydrase II as well as, late/functional differentiation markers; cathepsin K and matrix metalloproteinase 9 (MMP-9). Our data demonstrate that the aromatic amino acids down-regulated early and late osteoclastic differentiation markers as measured by real time PCR. Our data also suggest a link between the vitronectin receptor and the secreted cathepsin K that both showed consistent effects to the aromatic amino acid treatment. However, the non-attachment related proteins, calcitonin receptor, and carbonic anhydrase II, demonstrated less consistent effects in response to treatment. Our data are consistent with aromatic amino acids down-regulating osteoclastic differentiation by suppressing remodeling gene expression thus contributing initially to the net increase in bone mass seen in vivo.

Intensive glycemic control in gestational diabetes mellitus: a randomized controlled clinical feasibility trial.

BACKGROUND: Overweight and obese women with gestational diabetes mellitus are at increased risk for adverse perinatal outcomes, and they are also more likely to have suboptimal glycemic control. However, there is a paucity of data evaluating whether lower glycemic targets could improve outcomes. OBJECTIVE: To evaluate the feasibility of intensive glycemic control in overweight and obese women with gestational diabetes mellitus. MATERIALS AND METHODS: We randomized 60 overweight or obese women with gestational diabetes mellitus, diagnosed between 12 and 32 weeks' gestation to either intensive (fasting <90 mg/dL, 1 hour postprandial <120 mg/dL) or standard (fasting <95 mg/dL, 1 ho postprandial <140 mg/dL) glycemic targets. Maternal glucose was assessed in 2 ways: blinded continuous glucose monitors, worn for 5 days at 2 time points (at 12-32 weeks and again at 32-36 weeks), and self-monitored glucose measurement 4 times per day. All women underwent standardized dietary counseling, and medical therapy was prescribed as needed to achieve glycemic control. RESULTS: Between December 2015 and December 2017, we randomized 60 women to either intensive (n = 30) or standard (n = 30) glycemic control. Baseline characteristics including maternal age, body mass index, and gestational age at diagnosis were similar between the intensive and standard groups. Medical therapy was more common in women in the intensive group than those in the standard group (83 vs 57%, P = .02). Women in the intensive glycemic control group had lower glucose values as assessed by continuous glucose monitors at including 24-hour mean (-8.1; 95% confidence interval, -12.0 to -4.3 mg/dL; P < .0001) and 1-h postprandial (-11.8; 95% confidence interval, -19.7 to -3.9 mg/dL, P = .004) values. Hypoglycemia <60 mg/dL was uncommon and did not differ between groups. CONCLUSION: Intensive glycemic targets can be used in overweight and obese women with minimal hypoglycemia, and this approach results in improved glycemic control when compared to standard glycemic targets. Further studies are needed to determine whether intensive glycemic targets can improve maternal and neonatal outcomes in high-risk women with gestational diabetes mellitus. CLINICAL TRIAL IDENTIFIER: NCT02530866; clinicaltrials.gov.

Infection and preterm birth.

Preterm birth (PTB) remains a primary cause of neonatal morbidity and mortality. The purpose of this article is to outline the association between infection and PTB. We performed a search of the PubMed database for relevant scientific work published in English from 1995 to July 2015. Whereas there is substantial evidence regarding infection as a strong risk factor for preterm birth, the role of specific bacterial and viral infections is not totally conclusive. Newer high-dimensional biological technologies such as microbiomics and metabolomics offer hope to identify the causative pathogens. In addition, strategies have been developed to reduce PTB.