Antenatal toxoplasmosis screening and treatment in Northern Italy: update on the clinical effectiveness.

BACKGROUND: Antenatal universal screening for toxoplasmosis is recommended in most affluent countries worldwide. Despite evidence is not robust, detected cases are typically treated during pregnancy. Affected newborns are also treated to temper clinical consequences. However, this established mode of management warrants careful and continuous re-evaluation. The epidemiology of the infection is changing and there is the need to monitor the clinical scenario. METHODS: This is an observational retrospective study conducted at a referral hospital in Northern Italy. Every woman referred from January 2011 to December 2021 for suspected toxoplasmosis in pregnancy was eligible. All women were managed according to a local standardized protocol. Clinical and laboratory findings were obtained from patients' charts. RESULTS: Out of 347 women referred, 191 (55%) were discharged as false positive at initial assessment. We identified 141 women with suspected infection and 15 with confirmed infection. The number of women treated with antibiotics was 136 (96%) and 15 (100%), respectively. A total of 118 amniocenteses were performed, all of which were negative. There were two spontaneous miscarriages and five therapeutic terminations of pregnancy (of whom four were consequent to parental concerns related to the toxoplasmic infection), all among suspected cases. Vertical transmission occurred in a single case, a patient with confirmed infection diagnosed by seroconversion at 28 weeks' gestation. The course of this pregnancy was uneventful, and the infant is healthy at 7 years follow-up. Overall, the incidence of vertical transmission was 7% (95% CI: 1-30%) in confirmed cases and 0% (95% CI: 0-0.2%) in suspected cases. CONCLUSIONS: The current policy of universal screening and prompt management of toxoplasmosis infection is efficient. However, undue invasive procedures and terminations of pregnancy could occur. Future studies are warranted to improve clinical management.

Congenital Cytomegalovirus Infection With Isolated "Minor" Lesions at Fetal Magnetic Resonance Imaging: Long-Term Neurological Outcome.

BACKGROUND: The prognostic relevance of fetal/early postnatal magnetic resonance (MR) imaging (MRI) isolated "minor" lesions in congenital cytomegalovirus (CMV) infection is still unclear, because of the heterogeneity of previously reported case series. The aim of this study was to report the imaging and long-term clinical follow-up data on a relatively large cohort of infected fetuses. METHODS: Among 140 CMV-infected fetuses from a single-center 12-year-long fetal MRI database, cases that showed isolated "minor" lesions at MRI, mainly represented by polar temporal lesions, were selected. MRI features were described, and clinical follow-up information was collected through consultation of medical records and telephone interview to establish the auditory and neurological outcome of each patient. RESULTS: Thirty-six cases were included in the study. The frequency of "minor" lesions increased progressively with ongoing gestational age in cases who underwent serial MR examination; 31% of cases were symptomatic at birth for unilateral altered auditory brainstem response. At long-term clinical follow-up, performed in 35 patients at a mean age of 64.5 months (range: 25 to 138), 43% of patients were asymptomatic and 57% presented with mild/moderate disability including hearing loss (34%), unilateral in all cases but one (therefore classified as severe), and/or minor cognitive and behavioral disorders (49%). CONCLUSIONS: Descriptive analysis of the type and modality of occurrence of "minor" lesions suggests performing serial fetal/postnatal MR examinations not to miss later-onset lesions. Follow-up data from the present cohort, combined with maternal/fetal factors and serologic-laboratory parameters may contribute to improve prenatal and neonatal period counselling skills.

Preventing HIV mother-to-child transmission in a vertically infected pregnant woman with multiclass drug resistance, role of bis-in-die dolutegravir and neonatal AZT prophylaxis: A case report.

A suppressive antiretroviral therapy (ART) is necessary to prevent mother-to-child transmission (MTCT) of HIV during pregnancy. During this period, it is recommended to continue an ongoing safe and suppressive regimen, but history of multiclass drug-resistance (MDR) might need tailored, uncommon approaches posing tolerability and toxicity issues. This is the case of a 33 years of age, vertically infected woman with MDR HIV infection suppressed on a darunavir/cobicistat + atazanavir regimen switched during pregnancy to lamivudine + darunavir/ritonavir + dolutegravir 50 mg bis-in-die, maintaining complete viral suppression and delivering via caesarian section and without zidovudine (AZT) intrapartum prophylaxis a healthy HIV-negative newborn who received AZT post-exposure prophylaxis and showed regular growth patterns up to 2 years. Our case shows how archived MDR might complicate the preservation of HIV RNA suppression and highlights the importance of a tailored, multidisciplinary approach for pregnant women with MDR HIV and their newborns.

Risk of stillbirth in singleton fetuses with advancing gestational age at term: A 10-year experience of late third trimester prenatal screenings of 50,000 deliveries in a referral center in northern Italy.

BACKGROUND: The risk of intrauterine death (IUD) at term varies from less than one to up to three cases per 1,000 ongoing pregnancies. The cause of death is often largely undefined. Protocols and criteria to prevent and define the rates and causes of stillbirth are the subjects of important scientific and clinical debates. We examined the gestational age and rate of stillbirth at term in a 10-year period at our maternity hub to evaluate the possible favorable impact of a surveillance protocol on maternal and fetal well-being and growth. METHODS AND FINDINGS: Our cohort included all women with singleton pregnancies resulting in early term to late term birth at our maternity hub between 2010 and 2020, with the exclusion of fetal anomalies. As per our protocol for monitoring term pregnancies, all women underwent near term to early term maternal and fetal well-being and growth surveillance. If risk factors were identified, outpatient monitoring was initiated and early- or full-term induction was indicated. Labor was induced at late term (41+0-41+4 weeks of gestation), if it did not occur spontaneously. We retrospectively collected, verified, and analyzed all cases of stillbirth at term. The incidence of stillbirth at each week of gestation, was calculated by dividing the number of stillbirths observed that week by the number of women with ongoing pregnancies in that same week. The overall rate of stillbirth per 1000 was also calculated for the entire cohort. Fetal and maternal variables were analyzed to assess the possible causes of death. RESULTS: A total of 57,561 women were included in our study, of which 28 cases of stillbirth (overall rate, 0.48 per 1000 ongoing pregnancies; 95% CI: 0.30-0.70) were identified. The incidence of stillbirth in the ongoing pregnancies measured at 37, 38, 39, 40, and 41 weeks of gestation was 0.16, 0.30, 0.11, 0.29, and 0.0 per 1000, respectively. Only three cases occurred after 40+0 weeks of gestation. Six patients had an undetected small for gestational age fetus. The identified causes included placental conditions (n = 8), umbilical cord conditions (n = 7), and chorioamnionitis (n = 4). Furthermore, the cases of stillbirth included one undetected fetal abnormality (n = 1). The cause of fetal death remained unknown in eight cases. CONCLUSIONS: In a referral center with an active universal screening protocol for maternal and fetal prenatal surveillance at near and early term, the rate of stillbirth was 0.48 per 1000 in singleton pregnancies at term in a large, unselected population. The highest incidence of stillbirth was observed at 38 weeks of gestation. The vast majority of stillbirth cases occurred before 39 weeks of gestation and 6 of 28 cases were SGA, and the median percentile of the remaining case was the 35th.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

Minimal prevalence of HPV vaccination and common occurrence of high-risk HPV types in pregnant women with HIV: data from a national study in Italy.

Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.

An hypothetical external validation of the ARRIVE trial in a European academic hospital.

BACKGROUND: Recent evidence supports elective induction of labor at 39 weeks in low-risk pregnancies to improve maternal and perinatal outcomes. This evidence includes the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management). However, concerns have been raised on the external validity of the ARRIVE trial, especially with regard to the demographic and clinical characteristics of the pregnant women recruited. OBJECTIVE: This study compared the outcomes in a cohort of consecutive pregnant women, who fulfilled the criteria of the ARRIVE trial and were managed expectantly in an Italian referral academic hospital, with those reported in the expectant and induction arms of the ARRIVE trial. STUDY DESIGN: This was a retrospective single-center study. Consecutive low-risk nulliparous women who fulfilled the ARRIVE trial criteria were evaluated for eligibility at 36-38 weeks of gestation. Those who neither developed complications nor delivered spontaneously before 39 weeks were eligible for this comparative analysis. Maternal and fetal growth and wellbeing were screened and monitored from 36 to 38 weeks of gestation. RESULTS: A total of 1696 patients met the established criteria at recruitment. Of these, 343 spontaneously delivered in <39 weeks, 82 delivered because of maternal indication, and 37 for fetal indication. A total of 1234 pregnant women were eligible for comparison with the elective induction and the expectant management groups of the ARRIVE trial. The socioeconomic status was significantly better, maternal age was significantly higher, and body mass index was significantly lower in our cohort. Cesarean section rate in our cohort was lower than that of the expectant group of the ARRIVE trial (18.7 vs. 22.2%; p = 0.02) and similar to that of the elective induction group (18.7 vs. 18.6%). A new diagnosis of hypertensive disorders during expectant management was noted in 1.6% in our cohort vs. 14.1% in the ARRIVE arm. Among the different obstetric outcomes, only the prevalence of postpartum hemorrhage was not significantly lower in our cohort. The primary perinatal composite outcome was significantly better in our cohort than in both arms of the ARRIVE trial (2.1 vs. 5.4% in the expectant group and 4.3% in the induction group). We did not record cases with an Apgar score ≤ 3 or hypoxic-ischemic encephalopathy. CONCLUSION: In our cohort, expectant management in low-risk pregnancies with late preterm screening of feto-maternal well-being seemed to achieve better maternal and perinatal outcomes than a universal policy of induction at 39 weeks. The results of the ARRIVE trial should be carefully evaluated in different demographic and clinical settings and cannot be extended to the general population.

SARS-CoV-2 infection testing at delivery: a clinical and epidemiological priority.

BACKGROUND: Universal testing has been suggested as a useful strategy for a safe exit from the total lockdown, without recurrence of COVID-19 epidemic, delivering women being considered a sentinel population. Further universal testing for pregnant women may be useful in order to define appropriate access to COVID19 areas, dedicated neonatal care, and personal protective equipment. METHODS: During the period 10-26 April, all consecutive women admitted for delivery at the Maternity Hospitals of the city of Milan and in six provinces of Lombardy: Brescia, Como, Lecco Monza, Pavia, and Sondrio. areas were tested with nasopharyngeal swabs.Results and conclusion: Out of 1566 women, 49 were tested positive for SARS-Cov-2 (3.1%, 95% Confidence Interval (CI) 2.3-4.0). This value is largely higher than Heath Authorities estimate. Of tested positive women, 22 (44.9%) had symptoms or reported close contacts with positive patients, that is were found at risk by the itemized questionnaire. In conclusion, routine estimate of frequency of positivity among delivering women can be consider a useful methods to monitor positivity at least in females in their fertile ages.

Clinical relevance of SARS-CoV-2 infection in late pregnancy.

BACKGROUND: Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. METHODS: To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. RESULTS: Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. CONCLUSIONS: SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.

Sociodemographic characteristics of pregnant women tested positive for COVID-19 admitted to a referral center in Northern Italy during lockdown period.

INTRODUCTION: We investigated association between sociodemographic characteristics and COVID-19 disease among pregnant women admitted to our unit, the largest high-risk maternity unit in the Milan metropolitan area. METHODS: Between March 1, 2020 and April 30, 2020, 896 pregnant women were admitted to our Institution and tested for COVID-19. We collected information regarding their sociodemographic characteristics. Additional information on geographical area of residence, number of family members, number of family members tested positive for COVID-19, and clinical data was collected for women tested positive for COVID-19. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of developing COVID-19 according to sociodemographic characteristics were estimated by unconditional logistic regression models. RESULTS: Among the 896 women enrolled, 50 resulted positive for COVID-19. Pregnant women aged ≥35 years had a significantly lower risk of developing the infection (crude OR = 0.29; 95% CI:0.16-0.55). Conversely, foreign women (crude OR = 3.32; 95% CI:1.89-5.81), unemployed women (crude OR = 3.09; 95% CI: 1.77-5.40), and women with an unemployed partner (crude OR = 3.16; 95% CI: 1.48-6.79) showed a significantly higher risk of infection. Ethnicity was positively associated with the risk of developing COVID-19 (mutually adjusted OR = 2.15; 95% CI:1.12-4.11) in the multivariate analysis. Foreign women with COVID-19 were more likely to have a lower education level (p < 0.01), to be unemployed (p < 0.01), and to live in larger families (p < 0.01) compared to Italian pregnant women. CONCLUSIONS: The socioeconomic conditions described are characteristic of immigration patterns in our metropolitan area. These factors may increase the risk of viral transmission, reducing the effectiveness of lockdown and social distancing.

Prevalence, Correlates and Outcomes of Smoking in Pregnant Women with HIV: A National Observational Study in Italy.

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

Pregnancy and neonatal outcomes in women with HIV-1 exposed to integrase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors: an observational study.

PURPOSE: Recommended regimens for pregnant women with HIV-1 are composed of two nucleoside reverse transcriptase inhibitors (NRTI) plus either a ritonavir-boosted protease inhibitor (PI) or an integrase strand transfer inhibitor (ISTI), with non-nucleoside reverse transcriptase inhibitors (NNRTI) representing an alternative drug class. The study's purpose was to compare these three options in terms of pregnancy outcomes. METHODS: Data from a national observational study of pregnant women with HIV-1 were used. The analysis included all pregnancies reported between 2008 and 2018, ending in live births and exposed within 32 weeks of gestation to three-drug regimens composed of a NRTI backbone plus a PI, a NNRTI or a ISTI, without class switching during pregnancy. Clinical and laboratory outcomes were evaluated in univariate and multivariable analyses. RESULTS: Overall, 794 exposed pregnancies were analyzed (PI 78.4%, NNRTI 15.4%, ISTI 6.2%). Almost all outcomes had similar rates in the three groups. Women who received PI in pregnancy were less likely to be virologically suppressed at third trimester. PI use was associated with higher bilirubin and triglyceride levels, and ISTI use with a lower rate of low birthweight. The differences in viral suppression at third trimester and in low birthweight were not maintained in multivariable analyses that were adjusted for confounders. DISCUSSION: We found no major differences in a wide range of outcomes relevant for pregnant women with HIV. Such results are reassuring, and this information may be helpful in a context of preconception counseling when therapeutic choices for pregnancy are discussed between women and care providers.

Weight gain during pregnancy in women with HIV receiving different antiretroviral regimens.

BACKGROUND: No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. METHODS: Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. RESULTS: Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). CONCLUSIONS: No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.

BACKGROUND: There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. METHODS: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth (≥22 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. RESULTS: Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. CONCLUSIONS: Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss.

Vaginal delivery in women with HIV in Italy: results of 5 years of implementation of the national SIGO-HIV protocol.

PURPOSE: To evaluate the maternal and neonatal safety of vaginal delivery in women with HIV following the implementation of a national protocol in Italy. METHODS: Vaginal delivery was offered to all eligible women who presented antenatally at twelve participating clinical sites. Data collection and definition of outcomes followed the procedures of the National Program on Surveillance on Antiretroviral Treatment in Pregnancy. Pregnancy outcomes were compared according to the mode of delivery, classified as vaginal, elective cesarean (ECS) and non-elective cesarean section (NECS). RESULTS: Among 580 women who delivered between January 2012 and September 2017, 142 (24.5%) had a vaginal delivery, 323 (55.7%) had an ECS and 115 (19.8%) had an NECS. The proportion of vaginal deliveries increased significantly over time, from 18.9% in 2012 to 35.3% in 2017 (p < 0.001). Women who delivered vaginally were younger, more commonly nulliparous, diagnosed with HIV during current pregnancy, and antiretroviral-naïve, but had a slightly longer duration of pregnancy, with significantly higher birthweight of newborns. NECS was associated with adverse pregnancy outcomes. The rate of HIV transmission was minimal (0.4%). There were no differences between vaginal and ECS about delivery complications, while NECS was more commonly associated with complications compared to ECS. CONCLUSIONS: Vaginal delivery in HIV-infected women with suppressed viral load appears to be safe for mother and children. No cases of HIV transmission were observed. Despite an ongoing significant increase, the rate of vaginal delivery remains relatively low compared to other countries, and further progress is needed to promote this mode of delivery in clinical practice.

Zika Virus Infection in Pregnancy: Advanced Diagnostic Approaches in Dengue-Naive and Dengue-Experienced Pregnant Women and Possible Implication for Cross-Reactivity and Cross-Protection.

Zika virus (ZIKV) infection has been linked to congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil. Given the overlapping presence of Dengue virus (DENV) in the majority of ZIKV epidemic regions, advanced diagnostic approaches need to be evaluated to establish the role of pre-existing DENV immunity in ZIKV infection. From 2015 to 2017, five pregnant women with suspected ZIKV infection were investigated in Pavia, Italy. Among the five pregnant women, three were DENV-ZIKV immunologically cross-reactive, and two were DENV-naïve. Advanced diagnosis included the following: (i) NS1 blockade-of-binding (BOB) ELISA assay for ZIKV specific antibodies and (ii) ELISpot assay for the quantification of effector memory T cells for DENV and ZIKV. These novel assays allowed to distinguish between related flavivirus infections. The three DENV-experienced mothers did not transmit ZIKV to the fetus, while the two DENV-naive mothers transmitted ZIKV to the fetus. Pre-existing immunity in DENV experienced mothers might play a role in cross-protection.

Brief Report: Abacavir/Lamivudine and Tenofovir/Emtricitabine in Pregnant Women With HIV: Laboratory and Clinical Outcomes in an Observational National Study.

BACKGROUND: Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study. METHODS: Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC. RESULTS: The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P < 0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030). CONCLUSIONS: In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

Maternal Subcutaneous and Visceral Adipose Ultrasound Thickness in Women with Gestational Diabetes Mellitus at 24-28 Weeks' Gestation.

OBJECTIVE: To compare the sonographic measurement of maternal subcutaneous and visceral adipose thickness between pregnant women with gestational diabetes mellitus (GDM) and patients with nondiabetic pregnancies. METHODS: Adipose thickness was measured by transabdominal ultrasound in pregnant women attending our antenatal clinics at 24-28 weeks' gestation. All patients underwent a 75-g oral glucose challenge as a diagnostic test for GDM. RESULTS: The study population comprised 56 women with a positive glucose challenge test and 112 nondiabetic pregnancies. Measurements of subcutaneous and visceral adipose tissues were converted into multiples of the median (MoM), adjusted for gestational age. The mean subcutaneous thickness MoM in patients with GDM was significantly higher compared to nondiabetic pregnancies (1.31 vs. 1.07; p = 0.011). Similarly, the mean visceral thickness MoM was higher in women with a positive oral glucose tolerance test compared to controls (1.61 vs. 1.06; p < 0.001). Multivariate logistic regression analysis demonstrated that visceral adipose thickness, but not subcutaneous thickness, was significantly and independently associated with GDM (odds ratio 34.047, 95% confidence interval 9.489-122.166). CONCLUSIONS: Sonographic thickness of maternal visceral adipose tissue at 24-28 weeks' gestation was higher in women with GDM compared to nondiabetic pregnancies, independently from other known risk factors associated with GDM.