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Background: Women living with Human Immunodeficiency Virus are at higher risk of cervical cancer and precancer compared to women without HIV infection. The aim of the study is to evaluate the risk factors for the development of CIN2+ in a cohort of WLWH with negative colposcopy and cytology during a long follow-up period. Methods: We enrolled, in a multicentric retrospective cohort study, WLWH who attended the colposcopic services from 1999 to 2019. Patients with a normal Pap smear, a negative HR-HPV test, and at least one year of follow-up were considered for the anlysis. Results: The five-year cumulative incidence of histologically confirmed HSIL was 8.3% (95% CI = 2.6–13.6) among subjects with a CD4+ cell count of < 200 cells/µL at any visit and 2.1% (95% CI = 0.7–3.4, p = 0.001) in women with a CD4+ cell count of persistently > 200 cells/µL. In women with persistent HR-HPV infection, the five-year cumulative incidence of CIN 2+ was 6% (95% CI = 1.6–10.2) versus 2% (95% CI = 0.4–3.6, p = 0.012) in women without HPV infection. An HIV viremia of > 200 copies/mL, a CD4+ cell count of < 200 cells/µL, persistent HR-HPV infection, and smoking ≥10 cigarettes/day were all independent and statistically significant risk factors associated with the development of CIN2+ during follow-up. Conclusions: WLWH with good immune status and negative Pap smear and HR-HPV test have a low risk for CIN2+.

Fetal intracranial hemorrhage (ICH) may result from a wide array of causes, either associated with maternal or fetal risk factors. In the last decade, monogenic causes of susceptibility to fetal ICH have been described, in particular in association with COL4A1 and COL4A2 genes. A peculiar form of ICH is acute necrotizing encephalitis (ANE), which is characterized by a rapid‐onset severe encephalopathy following an abnormal inflammatory response to an otherwise banal infection. It usually affects healthy children and it is thought to be multifactorial, with a genetic predisposition. RANBP2 gene has been extensively associated with ANE susceptibility. We hereby present a unique case of a 42‐year‐old secundigravida with intrauterine fetal demise at 35 weeks of gestation. Trio‐based whole‐exome sequencing performed on both parents and fetal DNA showed a de novo likely pathogenic variant in the RANBP2 gene on 2q13. At the fetal autopsy, subtentorial hematoma and cerebral intraparenchymal hemorrhage were present. We speculate that this might be a new phenotypic presentation of RANBP2‐associated disease. However, more similar fetal cases need to be reported in order to reinforce this hypothesis.

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Background: Low-grade cervical lesions have a high percentage of clearance in young women, even if 71–82% of low-grade intraepithelial lesion/atypical squamous cells of undetermined significance (LSIL/ASCUS) reported a High-Risk Human Papillomavirus (HR-HPV) infection, which correlates with an increased risk of Cervical Intraepithelial Neoplasia (CIN)2+. The immunogenic effect of the anti-HPV vaccine appears to be significant. The aim of the study is to evaluate the effect, two years after the diagnosis, of the anti-HPV preventive vaccination on patients with low-grade cervical lesions. Methods: We collected clinical, colposcopic, histological, and virological data from patients aged 21–45 years who attended the colposcopy service of the department of Obsetrics and Gynecology of IRCCS Foundation Policlinico San Matteo, Pavia, Italy. In the 2005–2019 period and had a low-grade pap-smear. Results: We enrolled 422 women consecutively, divided into two groups (vaccinated and not vaccinated) for the retrospective analysis. The rate of persistence and progression of CIN were higher in the not-vaccinated group (p = 0.019). The relative risk (RR) to develop CIN2+ during follow-up vs. the the CIN1 persistence was 1.005 (95% Confidence Interval—CI 0.961–1.051) vs. 0.994 (95% CI 0.994–1.018) for age, 3.472 (95% CI 1.066–11.320) vs. 1.266 (95% CI 0.774–2.068) for non-vaccinated, 0.299 (95% CI 0.088–1.018) vs. 0.518 (95% CI 0.242–1.109) for HIV status negative, respectively. Analyzing the time to negativity, the odds ratio (OR) was 1.012 (95% CI 1–1.024) for age and 1.591 (95% CI 1.223–2.069) for vaccination; on the other hand, considering the relationship between the time to negative and the HPV genotypes contained in the 9-valent HPV vaccines, the OR was 1.299 (95% CI 1.026–1.646) for at least one of these at recruitment and 0.631 (95% CI 0.471–0.846) at follow-up. Furthermore, the presence of at least one of the HPV genotypes targeted by the HPV nonavalent vaccine is a key indicator of the risk of progression to CIN2+: OR was 3.443 (95% CI 1.065–11.189) for the presence of at least one HPV genotype at enrollment and 5.011 (95% CI 1.899–13.224) for the presence of at least one HPV genotype at follow-up, respectively. Conclusions: We reported in a retrospective study the benefit of anti-HPV vaccination in promoting negativity and increasing low-grade cervical lesions regression.

Introdcution: The purpose of this study was to evaluate the association between placental pathologic features of maternal (MVM) or fetal (FVM) vascular malperfusion and clinical characteristics, sonographic findings and neonatal outcome in a cohort of pregnancies complicated by early-onset (diagnosed before 32 weeks of gestational age) fetal growth restriction (FGR). Methods: A prospective cohort study included 250 singleton early-onset FGR pregnancies diagnosed, followed up and delivered at a single Centre. Elementary placental pathologic lesions were classified according to standard recommendations. Logistic regression and Cox analysis were used to evaluate outcomes adjusting for confounders. Results: Overall features of severe placental MVM and FVM were observed in 29.6% (74/250) and 12.8% (32/250) of the subjects, respectively. Severe placental MVM lesions were more common among subjects with umbilical artery (UA) Doppler Pulsatility Index > 95th than ≤ 95th percentile (50/120 as opposed to 24/130, Adj OR= 3, 95% CI = 1.6-5.4) and CerebroPlacental Ratio (CPR) < 5th than ≥5th percentile (48/115 as opposed to 26/135, Adj OR= 2.7, 95% CI = 1.5-4.9). Mean time from FGR diagnosis to delivery was shorter among subjects with severe MVM (25.5 days, 95% CI= 20.6-30.2, Adj. OR = 1.9,95% CI = 1.9,95% CI =1.4-2.5) when compared to both those with mild/moderate MVM (36.5 days (95% CI = 27-.2-45, p=0.04) or no MVM (39.4,95% CI = 35.4-43.4, p<.001). Finally, severe FVM was associated with an increased risk of perinatal/neonatal death or severe brain lesions (9/28 in subjects with perinatal/neonatal death/brain lesions as compared to 23/222 in controls, Adj OR= 3, 95% CI = 1.05-8.6) or severe adverse neonatal outcomes (13/46 in subjects with severe adverse outcome as compared to 19/204 among controls, Adj OR= 3.2, 95% CI =1.2-8.5). Conclusions: In early-onset FGR, placental pathologic features of MVM and FVM are distinct independent predictors of severity of clinical picture, abnormal Doppler markers of placental and fetal circulation and of neonatal outcome, respectively.