Early and mid-gestation Zika virus (ZIKV) infection in the olive baboon (Papio anubis) leads to fetal CNS pathology by term gestation.

Zika virus (ZIKV) infection in pregnancy can produce catastrophic teratogenic damage to the developing fetus including microcephaly and congenital Zika syndrome (CZS). We previously described fetal CNS pathology occurring by three weeks post-ZIKV inoculation in Olive baboons at mid-gestation, including neuroinflammation, loss of radial glia (RG), RG fibers, neuroprogenitor cells (NPCs) resulting in disrupted NPC migration. In the present study, we explored fetal brain pathologies at term gestation resulting from ZIKV exposure during either first or second trimester in the Olive baboon. In all dams, vRNA in whole blood resolved after 7 days post inoculation (dpi). One first trimester infected dam aborted at 5 dpi. All dams developed IgM and IgG response to ZIKV with ZIKV IgG detected in fetal serum. Placental pathology and inflammation were observed including disruption of syncytiotrophoblast layers, delayed villous maturation, partially or fully thrombosed vessels, calcium mineralization and fibrin deposits. In the uterus, ZIKV was detected in ¾ first trimester but not in second trimester infected dams. While ZIKV was not detected in any fetal tissue at term, all fetuses exhibited varying degrees of neuropathology. Fetal brains from ZIKV inoculated dams exhibited a range of gross brain pathologies including irregularities of the major gyri and sulci of the cerebral cortex and cerebellar pathology. Frontal cortices of ZIKV fetuses showed a general disorganization of the six-layered cortex with degree of disorganization varying among the fetuses from the two groups. Frontal cortices from ZIKV inoculation in the first but not second trimester exhibited increased microglia, and in both trimester ZIKV inoculation, increased astrocyte numbers (white matter). In the cerebellum, increased microglia were observed in fetuses from both first and second trimester inoculation. In first trimester ZIKV inoculation, decreased oligodendrocyte precursor cell populations were observed in fetal cerebellar white matter. In general, our observations are in accordance with those described in human ZIKV infected fetuses.

Clinical effectiveness of adding azithromycin to antimicrobial prophylaxis for cesarean delivery.

BACKGROUND: A recent large clinical trial demonstrated an approximately 50% decrease in the rate of postoperative infection in women who were laboring and/or had rupture of membranes for >4 hours and who received azithromycin in addition to standard preoperative antibiotic prophylaxis at the time of cesarean delivery. Given these results, our institution made a policy change in May 2017 to add azithromycin to standard preoperative prophylaxis for all cesarean deliveries. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of adding azithromycin to preoperative antibiotic prophylaxis for cesarean delivery. STUDY DESIGN: We conducted a before-and-after cohort study of women delivered via cesarean delivery at our institution. The preimplementation group included women who delivered from March 1, 2016, to February 28, 2017, (before an institutional practice change of adding azithromycin to standard preoperative prophylaxis), and the postimplementation group included women who delivered from September 1, 2017, to August 31, 2018 (allowing a 6-month period for uptake of the practice change). The primary outcome was a composite of postoperative infections (endometritis, wound infection, other maternal infections). Unadjusted and adjusted risk ratios and 95% confidence intervals were estimated using a modified Poisson regression model. RESULTS: In the preimplementation (n=1171) and postimplementation (n=1168) groups, the incidence rates of the composite outcomes were 4.7% and 5.3%, respectively (P=.49). Both unadjusted (relative risk, 1.13; 95% confidence interval, 0.78-1.62) and adjusted (adjusted relative risk, 1.06; 95% confidence interval, 0.74-1.52) comparisons were not significantly different. In addition, results were statistically nonsignificant, but in the direction of lower rates of infection, in the after cohort for women in labor and/or with rupture of membranes for ≥4 hours (relative risk, 0.88 [95% confidence interval, 0.56-1.39]; adjusted relative risk, 0.82 [95% confidence interval, 0.52-1.30]) and for women with clinical chorioamnionitis (relative risk, 0.37 [95% confidence interval, 0.08-1.67]; data too sparse for adjusted analysis). In the subgroup of women who were not in labor, the after cohort had a statistically nonsignificant increased risk of the composite outcome in both unadjusted (relative risk, 1.53; 95% confidence interval, 0.86-2.72) and adjusted (adjusted relative risk, 1.48; 95% confidence interval, 0.83-2.65]) comparisons. CONCLUSION: In clinical practice, the addition of azithromycin to standard preoperative antibiotic prophylaxis for cesarean delivery may have an effect size smaller than seen in the large clinical trial prompting this practice change. Extrapolation of this regimen to women not in labor may be ineffective.

Prenatal diagnosis of middle interhemispheric variant of holoprosencephaly: Report of two cases.

Holoprosencephaly ranges in severity based on the degree of anatomic abnormality. Middle interhemispheric variant of holoprosencephaly is a less common and often milder variant that has the characteristic sonographic findings of an absent cavum septum pellucidum and a single fused ventricle. This subtype may be associated with genetic conditions that have not been well-described in the literature. We present two cases of middle interhemispheric variant of holoprosencephaly diagnosed on fetal ultrasound.