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Objective: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations., Methods: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years., Results: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes., Conclusion: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia., Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed., Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p  = 0.03), as well as prematurity (81.8% vs 41.6%, p  = 0.02), low birth weight (63.6% vs 24.7%, p  = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p  = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant., Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia., Competing Interests: The authors declare there are no competing interests., (©2024 Sobieray et al.)

Africa has the highest number of pregnant women with human immunodeficiency virus (HIV). In some studies, HIV has been associated with adverse perinatal outcomes. However, the pathophysiological mechanism leading to adverse fetal outcomes is not known. Maternal vascular malformation, chorioamnionitis, and decreased placental weight have been described as placental features associated with HIV in some studies. The use of antiretroviral therapy has reduced perinatal transmission of HIV and adverse fetal outcomes. However, placental mechanisms associated with HIV and the fetal immune response to maternal HIV infection are poorly understood. Additional research is required to understand whether altered maternal immunity in women living with HIV can trigger fetal responses leading to stillbirth or preterm birth., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections having been associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition., (© 2021 Wiley Periodicals LLC.)

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission., Competing Interests: FSFG is a consultant and has a funded research agreement with Biotheus Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rad, Röhl, Stylianou, Allenby, Bazaz, Warkiani, Guimaraes, Clifton and Kulasinghe.)

Purpose: To compare the performance of a local estimated fetal weight curve with curves established for other populations to predict small for gestational age (SGA) fetuses., Methods: A retrospective and cross-sectional study involving 231 fetuses in which the performance of a local curve (proposed model) was compared with the Hadlock and Intergrowth-21st curves in the prediction of SGA fetuses, by applying them to a population of high-risk pregnant woman with HIV/AIDS. For each model, a receiver operating characteristic curve was adjusted, considering the SGA classification by the neonatal Intergrowth method as the gold standard, and the area under the curve (AUC) was calculated., Results: The models presented linear correlations with each other. The agreement of the proposed model with Hadlock was very good (kappa = 0.83), whereas the proposed model and Intergrowth-21st had moderate agreement (kappa = 0.44). The SGA fetus detection sensitivities of the proposed model and Hadlock were 61.9% and 57.1%, with specificity of 84.1% and 86.2% and accuracy of 80.1% and 81%, respectively, without statistical difference. The sensitivity of the Intergrowth-21st model was 33.3%, while the accuracy was 85.7% and the specificity was 97.4%. The AUC estimated values for the Hadlock, proposed, and Intergrowth-21st models were 0.834, 0.832, and 0.835, respectively., Conclusion: The proposed model and Hadlock were interchangeable in the prediction of SGA fetuses and superior to the Intergrowth-21st model., (© 2020 Wiley Periodicals LLC.)

Objective: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry., Methods: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection., Results: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM., Conclusions: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd.)

Human herpesviruses 6A (HHV-6A) and human herpesvirus 6B (HHV-6B)-collectively, HHV-6A/B-are recently-discovered but ancient human viruses. The vast majority of people acquire one or both viruses, typically very early in life, producing an ineradicable lifelong infection. The viruses have been linked to several neurological, pulmonary and hematological diseases. In early human history, the viruses on multiple occasions infected a germ cell, and integrated their DNA into a human chromosome. As a result, about 1% of humans are born with the full viral genome present in every cell, with uncertain consequences for health. HHV-6A may play a role in 43% of cases of primary unexplained infertility. Both the inherited and acquired viruses may occasionally trigger several of the factors that are important in the pathogenesis of preeclampsia. Transplacental infection occurs in 1-2% of pregnancies, with some evidence suggesting adverse health consequences for the child. While emerging knowledge about these viruses in reproductive diseases is not sufficient to suggest any changes in current practice, we write this review to indicate the need for further research that could prove practice-changing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Komaroff, Rizzo and Ecker.)

In this six-year study, there were 1118 newborn genetic testing; there were 162 genetic testing for symmetrically growth retarded infants. Out of this, only six infants had positive results yielding a low odds ratio of 0.21 for having any significant chromosome results. Urine CMV testing was positive only in one infant out of 118 tested., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes., Methods: We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies., Results: From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19-1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11-3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08-1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01-1.37), low birth weight (aOR, 1.91; 95% CI, 1.33-2.76), and fetal death (aOR, 2.23; 95% CI, 1.14-4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40-3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80-1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained., Conclusions: We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

It is common practice to screen for human cytomegalovirus (CMV) and herpes simplex virus (HSV) among women with infertility problems, recurrent abortion or exhibiting intrauterine growth restriction during pregnancy. Nonetheless, limited information exists about the incidence of these viruses in Saudi Arabia. The IgG and IgM antibodies of 761 women and 85 of neonates who showed intrauterine growth retardation (IUGR) were reviewed against cytomegalovirus and herpes simplex virus-1. Tests were repeated only for those with positive results. Recent infection of herpes simplex virus-1 and cytomegalovirus was evidenced by the presence of IgM in the female patients: incidence was 1.1% and 1.3% respectively. None of the neonates showed positive IgM for cytomegalovirus, but a single case showed a positive result for herpes simplex virus-1 IgM. Among the female patients, however, the presence of IgG indicated previous exposure to cytomegalovirus in 92% of cases and herpes simplex virus in 80.8%. It was concluded that although previous exposure to CMV and HSV-1 were found in high percentages in women experiencing infertility problems but did not appear to be associated with neonates exhibiting intrauterine growth retardation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This case report describes the clinical findings of a 22-year-old pregnant woman with confirmed Zika virus infection, at 16 weeks of gestation, in Sucre, Colombia. Her ultrasound revealed severe oligohydramnios, intrauterine growth restriction, and a complete absence of the urinary bladder of the fetus. The poor prognosis led to the decision to terminate the pregnancy. Autopsy of the fetus revealed severe bilateral renal hypoplasia., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR)., Study Design: Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth., Results: One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine β-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection., Conclusions: Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To present the currently available evidence of the effects of congenital Zika virus infection on infant growth, to discuss possible intervening factors, and to describe preliminary data on this growth in a cohort of exposed children., Source of Data: Non-systematic review in PubMed, BVS, CAPES, Scopus, Web of Science, Cochrane and Google Scholar databases in the last 5 years, using the terms infection/disease by Zika virus and growth/nutrition/nutritional status/infant nutrition and nutritional needs. Additionally, the anthropometric data of the first 2.5 years of a cohort of children exposed to the Zika virus during pregnancy were reviewed., Synthesis of Data: Both intrauterine growth restriction and low birth weight were reported in series of cases of children with congenital Zika syndrome. The postnatal growth deficit of these children appears to be directly proportional to the degree of neurological impairment. The etiology is multifactorial, and nutritional and non-nutritional factors are probably involved. The data from the present cohort show that the head circumference evolution depends on this measurement at birth and that weight-height growth has a trend toward lower weight and length in children with congenital microcephaly and normocephalic at birth who develop some neurological abnormality., Conclusions: The few existing data suggest that, in children with congenital Zika, the greater the degree of neurological impairment, the greater the impact on growth, whether or not associated with microcephaly at birth., (Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: Using unbiased population data, to examine whether having a positive Pap smear, and thus a high probability of Human Papilloma Virus (HPV) infection, is a significant risk factor for intrauterine growth restriction (IUGR) in a subsequent pregnancy., Study Design and Methods: Two independent population-based databases, namely the South Australian Perinatal Statistics Collection and the South Australian Cervical Screening Database, were deidentified and linked by the SANT Datalinkage Service. Analyses were performed on cases where Pap smear screening data was available for up to 2 years prior to a singleton live birth. Population characteristics and pregnancy related data were compared statistically by normal birth weight versus IUGR (10th percentile - known as small for gestational age (SGA), small for gestational age) and (3rd percentile birth weight - known as VLBW, very low birth weight). The association between cervical screening results and IUGR was assessed using generalized linear log binomial regression models., Results: A total of 31,827 women met the criteria. Of these, 1311 women (4.1%) had a positive Pap smear within 2 years of the current pregnancy. Those having a positive Pap smear were more likely to have a baby with IUGR than those with negative smear results. For SGA, 5.8% babies were from mothers with positive Pap smears compared to 4.0% with negative smears indicating a 40% higher risk of having an SGA baby (95%CI 20-70%) among women with positive Pap smears. For VLBW, 7.6% mothers had positive Pap smears compared with 4.0% with negative smears (p < .001), which reflects a 90% increased risk (95%CI 40-150%). These associations reduced to 20% (95%CI 1-40%) and 50% (95%CI 10-100%) for SGA and VLBW, respectively, after adjusting for all other significant covariates including maternal age, ethnicity, marital status, occupation, smoking, pregnancy history, and maternal health during pregnancy., Conclusions: Mothers with a positive Pap smear have an increased risk of IUGR, especially for VLBW, which is independent of other risk factors. The results confirm previous findings in a small study and emphasise the need to consider the risks of both cancer and IUGR in all HPV vaccination programs.

Zika virus (ZIKV) can cause various diseases in offspring after congenital infection. The purpose of this study was to identify disease phenotypes in pups exposed to ZIKV in utero. Female interferon-α/β, -γ receptor knockout mice (AG129) were infected intraperitoneally with ZIKV 7.5 days' post coitus (dpc). Viral RNA, antigen and infectious virus were detected in some, but not all, maternal and fetal tissues at various times during gestation. Fetuses of infected dams had significant intrauterine growth restriction (IUGR), which was more pronounced as females neared parturition. Pups born to infected dams were significantly smaller and had significantly shortened skull lengths, as determined by measurement with a caliper and by micro-CT analysis, as compared with age-matched controls. Growth rates of exposed pups after birth, however, was similar to sham-exposed offspring. Viral RNA was detected in pups of infected dams after birth. A lower survival rate was observed in neonates exposed to ZIKV in utero. A mortality rate of over 50%, attributed to consequences of ZIKV infection, occurred after birth in pups born to infected dams. A transient hearing loss was observed in some animals exposed to virus in utero. No motor deficits or cognitive deficits were detected using running wheel or viral paresis scoring assays. Abnormalities in offspring included smaller size, shorter skull length and increased neonatal mortality, while the only functional deficit we could detect was a low incidence of transient hearing loss.

This article reviews the sonographic manifestations of fetal infection and the role of ultrasound in the evaluation of the fetus at risk for congenital infection. Several ultrasound findings have been associated with in utero fetal infections. For the patient with a known or suspected fetal infection, sonographic identification of characteristic abnormalities can provide useful information for counseling and perinatal management. Demonstration of such findings in the low-risk patient may serve to identify the fetus with a previously unsuspected infection. The clinician should understand the limitations of ultrasound in the prenatal diagnosis of congenital infection and discuss them with the patient.

Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout ( Ifnar1 -/- ) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling. The role of type I IFNs in limiting or mediating ZIKV disease within this congenital infection model remains unknown. In this study, we challenged Ifnar1 -/- dams mated with Ifnar1 +/- sires with ZIKV. This breeding scheme enabled us to examine pregnant dams that carry a mixture of fetuses that express ( Ifnar1 +/- ) or do not express IFNAR ( Ifnar1 -/- ) within the same uterus. Virus replicated to a higher titer in the placenta of Ifnar1 -/- than within the Ifnar1 +/- concepti. Yet, rather unexpectedly, we found that only Ifnar1 +/- fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1 -/- littermates continue to develop. Analyses of the fetus and placenta revealed that, after ZIKV infection, IFNAR signaling in the conceptus inhibits development of the placental labyrinth, resulting in abnormal architecture of the maternal-fetal barrier. Exposure of midgestation human chorionic villous explants to type I IFN, but not type III IFNs, altered placental morphology and induced cytoskeletal rearrangements within the villous core. Our results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The 2015 Zika virus (ZIKV) epidemic in the Americas led to the discovery that ZIKV causes congenital abnormalities including microcephaly, intrauterine growth restriction, and eye disease that can result in blindness. Studies in animal models and human organoid cultures, together with human epidemiological studies, have shown that ZIKV crosses the placenta and subsequently replicates within fetal tissues including the developing brain. Preferential infection of neural cell precursors causes damage to the developing fetal brain. However, a majority of congenitally infected humans do not develop microcephaly or other overt congenital abnormalities, so longitudinal epidemiological studies are necessary to more completely define the long-term consequences of in utero ZIKV infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise. In addition, prophylactic and therapeutic treatment of IFN-λ1 in a human trophoblast line, as well as in primary human amniotic epithelial cells, greatly reduced the ZIKV burden. Our data highlight IFN-λ1 as a potential therapeutic useful for women at risk for congenital Zika disease., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations., Methods: We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays., Results: Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth-associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers., Conclusions: This study identified several key markers for the control of ZIKV pathogenesis. This will allow a better understanding of the molecular mechanisms of ZIKV infection in patients., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Maternofoetal infection with Cytomegalovirus (CMV) is the most common congenital infection and a leading cause of mental retardation and sensori-neural hearing loss. Population-based studies indicate that at least 0.5% of all infants born alive have CMV of whom approximately 10% have clinically evident symptomsat birth. The Justification of systematic screening for foetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when foetal infection has been diagnosed. In case of congenital CMV infection, infants can be symptomatic or asymptomatic at birth. Mortality for such infants can reach 30%, and survivors can have mental retardation, sensorineural hearing loss, chorioretinitis, and other significant medical problems. A newborn symptomatic is defined by the existence of clinical and / or biological signs and / or neonatal imaging, the most frequent clinical signs are: hepatosplenomegaly (60%), microcephaly (53%), jaundice (67%), petechiae (76%), at least one neurological abnormality (68%). The frequency of biological abnormalities is as follows: increase in transaminases (83%), thrombocytopenia (77%), hyperbilirubinemia (69%), haemolysis (51%), hyperproteinorrachy (46%). The abnormalities of neonatal imaging are present in 70% of symptomatic newborns; intracerebral calcifications are the most frequent abnormalities. We report a case of newborn who presented a congenital infection by CMV, evoked on the intrauterine growth retardation, organs of the reticulo endothelial and haematological system were reached while nervous system was spared, and CMV PCR was very positive. indicating an antiviral treatment for 6weeks based on ganciclovir.

Zika virus (ZIKV) can be transmitted by mosquito bite or sexual contact. Using mice that lack the type I interferon receptor, we examined sexual transmission of ZIKV. Electron microscopy analyses showed association of virions with developing sperm within testes as well as with mature sperm within epididymis. When ZIKV-infected male mice were mated with naive female mice, the weight of fetuses at embryonic day 18.5 was significantly reduced compared with the control group. Additionally, we found ocular deformities in a minority of the fetuses. These results suggest that ZIKV causes fetal abnormalities after female mating with an infected male., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Zika virus (ZIKV) has been linked to intrauterine growth restriction (IUGR), spontaneous miscarriage, and microcephaly in infants of women infected during pregnancy. To determine how ZIKV affects the fetus, we infected pregnant mice subcutaneously (mimicking a mosquito bite) with ZIKV. Multiple techniques revealed that ZIKV replicated within placental trophoblasts, fetal endothelial cells, and the fetal neocortex. We also noted severe placental defects, IUGR, and fetal death. Thus, our mouse model recapitulated ZIKV infection in human pregnancy and demonstrated that ZIKV can be transmitted from mother to fetus via the placenta.

The Aim: To study the impact of emergent infections (human herpesvirus type 6) on the fetal state., Materials and Methods: The study involved examination of 90 pregnant women in the 2nd and 3rd trimesters of gestation (Group 1 (25 pregnant) consisted of patients with a viral infection, CMV carriers, Group 2 (25 pregnant) included women with a viral infection, herpes simplex virus types 1/2, Group 3 amounted for 20 patients with a viral infection, herpes simplex virus type 6, Group 4 comprised 20 patients with normal pregnancy and no signs of infection. Concentration of IgM and IgG to herpes simplex virus types 1/2, IgM and IgG to herpesvirus type 6 in venous blood of the pregnant was determined by enzyme-immunoassay. Giant cells typical for CMV were determined by cytological examination of saliva sediment. All the pregnant underwent ultrasound somatogenetic examination, Doppler evaluation of maternal-placental-fetal hemodynamics and biophysical profile (BPP) assessment. Results and their discussion: Ultrasound examination of Group 1, 2 and 3 pregnant showed signs of intrauterine infection. Pregnant women with a viral infection were found to have intrauterine growth retardation (IUGR) and Group 3 patients more commonly had symmetrical 3rd degree IUGR. BPP indices showed initial signs of fetal distress in 5 (20%) Group 1 pregnant, 7 (27%) Group 2 pregnant and 11 (55%) Group 3 pregnant women. Doppler examination of uterine-feto-placental hemodynamics revealed a more pronounced increase in vascular resistance indices in Group 3 patients., Conclusions: Emergent infections (herpesvirus type 6) of pregnant trigger more pronounced changes in the feto-placental system than other viral infections. Herpesvirus type 6 is a common cause of fetal state deterioration, which manifests in intrauterine growth retardation, changes in biophysical profile and hemodynamic disorders in the mother-placenta-fetus system.

Background: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants., Methods: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes., Results: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester)., Conclusions: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

Zika virus (ZIKV) infection of pregnant women can result in fetal brain abnormalities. It has been established that ZIKV disrupts neural progenitor cells (NPCs) and leads to embryonic microcephaly. However, the fate of other cell types in the developing brain and their contributions to ZIKV-associated brain abnormalities remain largely unknown. Using intracerebral inoculation of embryonic mouse brains, we found that ZIKV infection leads to postnatal growth restriction including microcephaly. In addition to cell cycle arrest and apoptosis of NPCs, ZIKV infection causes massive neuronal death and axonal rarefaction, which phenocopy fetal brain abnormalities in humans. Importantly, ZIKV infection leads to abnormal vascular density and diameter in the developing brain, resulting in a leaky blood-brain barrier (BBB). Massive neuronal death and BBB leakage indicate brain damage, which is further supported by extensive microglial activation and astrogliosis in virally infected brains. Global gene analyses reveal dysregulation of genes associated with immune responses in virus-infected brains. Thus, our data suggest that ZIKV triggers a strong immune response and disrupts neurovascular development, resulting in postnatal microcephaly with extensive brain damage., Competing Interests: The authors declare no competing or financial interests., (© 2016. Published by The Company of Biologists Ltd.)

Human cytomegalovirus (HCMV) is the leading viral cause of birth defects, including microcephaly, neurological deficits, hearing impairment, and vision loss. We previously reported that epithelial cells in amniotic membranes of placentas from newborns with intrauterine growth restriction and underlying congenital HCMV infection contain viral proteins in cytoplasmic vesicles. Herein, we immunostained amniotic membranes from 51 placentas from symptomatic and asymptomatic congenital infection with HCMV DNA in amniotic fluid and/or newborn saliva, intrauterine growth restriction, preterm deliveries, and controls. We consistently observed HCMV proteins in amniotic epithelial cells (AmEpCs) from infected placentas, sometimes with aberrant morphology. Primary AmEpCs isolated from mid-gestation placentas infected with pathogenic VR1814 proliferated and released infectious progeny for weeks, producing higher virus titers than late-gestation cells that varied by donor. In contrast to intact virion assembly compartments in differentiated retinal pigment epithelial cells, infected AmEpCs made dispersed multivesicular bodies. Primary AmEpCs and explants of amniochorionic membranes from mid-gestation placentas formed foci of infection, and interferon-β production was prolonged. Infected AmEpCs up-regulated anti-apoptotic proteins survivin and Bcl-x L by mechanisms dependent and independent of the activated STAT3. Amniotic membranes naturally expressed both survivin and Bcl-x L , indicating that fetal membranes could foster persistent viral infection. Our results suggest strengthening innate immune responses and reducing viral functions could suppress HCMV infection in the fetal compartment., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40-1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43-2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population., Competing Interests: The authors have no conflicts of interest to disclose.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

The severity of porcine reproductive and respiratory syndrome was compared in pregnant gilts originating from high and low birth weight litters. One-hundred and eleven pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus on gestation day 85 (±1) were necropsied along with their fetuses 21 days later. Ovulation rates and litter size did not differ between groups, but fetuses from low birth weight gilts were shorter, lighter and demonstrated evidence of asymmetric growth with large brain:organ weight ratios (i.e. brain sparing). The number of intrauterine growth retarded fetuses, defined by brain:organ weight ratios greater than 1 standard deviation from the mean, was significantly greater in low, compared to high, birth weight gilts. Although γδ T cells significantly decreased over time in high compared to low birth weight gilts, viral load in serum and tissues, gilt serum cytokine levels, and litter outcome, including the percent dead fetuses per litter, did not differ by birth weight group. Thus, this study provided no substantive evidence that the severity of porcine reproductive and respiratory syndrome is affected by dam birth weight. However, intrauterine growth retarded fetuses had lower viral loads in both fetal thymus and in endometrium adjacent to the umbilical stump. Crown rump length did not significantly differ between fetuses that survived and those that died at least one week prior to termination. Taken together, this study clearly demonstrates that birth weight is a transgenerational trait in pigs, and provides evidence that larger fetuses are more susceptible to transplacental PRRSv infection.

Background: In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China., Methods: In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15-20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes., Results: The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01-6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes., Conclusions: In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes.

Background: Human cytomegalovirus (HCMV) is the major viral etiology of congenital infection and birth defects. Fetal transmission is high (30%-40%) in primary maternal infection, and symptomatic babies have permanent neurological, hearing, and vision defects. Recurrent infection is infrequently transmitted (2%) and largely asymptomatic. Congenital infection is also associated with intrauterine growth restriction (IUGR)., Methods: To investigate possible underlying HCMV infection in cases of idiopathic IUGR, we studied maternal and cord sera and placentas from 19 pregnancies. Anti-HCMV antibodies, hypoxia-related factors, and cmvIL-10 were measured in sera. Placental biopsy specimens were examined for viral DNA, expression of infected cell proteins, and pathology., Results: Among 7 IUGR cases, we identified 2 primary and 3 recurrent HCMV infections. Virus replicated in glandular epithelium and lymphatic endothelium in the decidua, cytotrophoblasts, and smooth muscle cells in blood vessels of floating villi and the chorion. Large fibrinoids with avascular villi, edema, and inflammation were significantly increased. Detection of viral proteins in the amniotic epithelium indicated transmission in 2 cases of IUGR with primary infection and 3 asymptomatic recurrent infections., Conclusions: Congenital HCMV infection impairs placental development and functions and should be considered as an underlying cause of IUGR, regardless of virus transmission to the fetus.

Aim: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR)., Methods: Maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of PE and/or FGR, and from 49 women with uneventful pregnancies (controls). Serum samples were evaluated by immunoblot assay for presence of specific antibodies against H. pylori antigens [virulence: cytotoxin-associated antigen A (CagA); ureases; heat shock protein B; flagellin A; persistence: vacuolating cytotoxin A (VacA)]. Maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer., Results: A significantly higher percentage of H. pylori seropositive women were found among PE cases (85.7%) compared to controls (42.9%, P < 0.001). There were no differences between pregnancies complicated by FGR without maternal hypertension (46.2%) and controls. Importantly, persistent and virulent infections (VacA/CagA seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by FGR, while virulent but acute infections (CagA positive/VacA negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with PE without FGR., Conclusion: Our data strongly indicate that persistent and virulent H. pylori infections cause or contribute to PE complicated by FGR, but not to PE without feto-placental compromise.

Background: Small for gestational date (SGA) babies have a poor 'whole of life' prognosis and major factors affecting SGA may be present prior to conception., Aims: To discover whether lifestyle risk factors can be identified in women planning a pregnancy., Study Design: Prospective study of women who were planning a pregnancy, who agreed to answer a detailed 250 question questionnaire prior to commencing to try to conceive, to being monitored, and within 7days of a positive pregnancy test having a vaginal ultrasound scan and answering further questions about the events since the last menstrual period. Details of all outcomes were recorded., Subjects: 585 couples completed the study., Outcome Measures: The relationships between birth weights and questionnaire data was analysed using SPSS and parametric statistical analysis., Results and Conclusions: 401 women (67.9% of all participants) had live births. Eleven babies (2.7%) were less than the 3rd percentile in weight and a further 22 babies (5.4%) were between the 3rd and 10th weight percentiles. Mothers of SGA babies had a lower than average education, diets that were low in meat, fish, dairy foods and nuts or seeds and were more likely to conceive in the winter. Mothers of SGA babies were significantly more likely to have had a recent abnormal Pap smear test. Air travel in the month of conception was a risk factor in having a baby less than 10th percentile., Conclusion: The quality of lifestyle prior to conception is critical: prenatal counselling needs to be undertaken prior to conception., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Epstein-Barr virus (EBV) infection in pregnancy and consequent fetal outcomes are rarely reported. The majority of cases described strongly support the possibility of transmission of this virus in utero and during delivery, resulting in stillbirth and/or congenital defects. We present a case of EBV reactivation in pregnancy that caused a severe symmetrical fetal growth restriction (FGR) and ultimately spontaneous fetal death. A 36-year-old woman, whose infection status was undetermined, was diagnosed with severe FGR at 24 weeks' gestation. The fetal karyotype was normal. EBV DNA was detected in the amniotic fluid and maternal immunoglobulin G antibodies were positive. At 30 weeks' gestation, the fetus died spontaneously. Placental examination found evidence of deciduitis and villitis. Reactivation of EBV infection appears to be related to FGR and warrants further research to determine the optimal management strategy in pregnancy., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Objective: To evaluate adverse pregnancy outcome in HIV infected women who received highly active antiretroviral therapy (HAART) from early pregnancy compared with untreated-maternal HIV infection., Study Design: A cohort study., Place and Duration of Study: Antenatal clinic, University of Benin Teaching Hospital, Nigeria, from January 2008 to June 2009., Methodology: Two hundred and forty nine HIV infected women who had intrapartum care constituted the study population. Unbooked HIV positive pregnant women, who had not received antiretroviral drugs during the antenatal period but received nevirapine in labour, referred to as untreated-maternal HIV infection, were compared with women who received HAART early in pregnancy. Outcome measures of interest were obstetric complications and perinatal outcome proportion., Results: Intrauterine growth restriction (IUGR) (20.5% vs. 6.3%, p = 0.003), pre-term birth (25.0% vs. 9.8%, p = 0.005) and caesarean delivery (45.5% vs. 29.8%, p = 0.04) were significantly higher among women with untreated-HIV infection in pregnancy compared with women who received HAART from early pregnancy. Untreated maternal HIV-infection was associated with higher frequency of birth weight less than 2500g, 5-minutes Apgar score less than 7 and admission into neonatal unit (p < 0.05). Women with primary education were significantly higher in the group with untreated maternal HIV infection (27.3% vs. 12.7%, p = 0.003)., Conclusion: Untreated maternal HIV-infection in pregnancy may be associated with adverse pregnancy outcome. HIV positive women with low level of education utilise PMTCT services suboptimally. This information is important for programmes designed to increase access to PMTCT services including HAART from early pregnancy.

Background: Pregnant women are at increased risk for complications from seasonal influenza. Early data suggest that influenza A (H1N1) may present an even greater risk., Case: We present the case of a pregnant woman with severe pulmonary complications from 2009 H1N1 whose care was further complicated by delay in diagnosis and unusual laboratory abnormalities., Conclusion: H1N1 may pose several diagnostic challenges for obstetricians, including increased rates of serious pulmonary complications, decreased sensitivity of rapid tests with delay in initiation of antiviral therapy, and abnormal laboratory findings usually associated with other complications of pregnancy. We document these problems, urge initiation of antiviral therapy based on clinical suspicion, and recognize the potential laboratory abnormalities that may be associated with severe influenza illness.

A term newborn with severe congenital cytomegalovirus (CMV) infection is described. Fetal ascites was detected at 28 weeks gestation, and at birth there was tense ascites. There was intra-uterine growth retardation, microcephaly, chorioretinitis, jaundice, purpura and pneumonitis. Computed tomographic scan of the brain showed ventriculomegaly with periventricular calcifications. Serology was positive for cytomegalovirus-specific immunoglobulin M, and cytomegalovirus DNA was detected in the ascitic fluid and urine by nested polymerase chain reaction. He received 6 weeks of treatment with ganciclovir. Ascites resolved spontaneously and liver function tests became normal. Although there was a good clinical response to ganciclovir therapy without any side-effects, on follow-up the infant had global developmental delay and bilateral sensorineural deafness.

Objectives: To describe our experience in cases with sonographic signs of fetal infection and with maternal serological 'immunity' to cytomegalovirus (CMV) infection., Methods: This was a bicenter study of six pregnant women referred for evaluation of suspected fetal infection. All cases had confirmed maternal serology for past exposure to CMV but no evidence of recent secondary CMV infection. All underwent sonographic evaluation as well as complete investigation for CMV infection., Results: The mean age of the women was 29 (range, 23-35) years and the mean gestational age at diagnosis was 23.5 weeks (range, 20-31) weeks. Sonographic findings included microcephaly, ventriculomegaly, periventricular calcifications and cystic lesions, echogenic bowel, hydrops and hepatosplenomegaly. Amniocentesis was performed in all cases for fetal karyotyping and viral assessment, and all were found by polymerase chain reaction to be positive for CMV infection. Four pregnancies were terminated following the parents' request. One pregnancy continued until intrauterine fetal death occurred 2 weeks after diagnosis. Postmortem was denied in all cases but one. One infant was delivered with evidence of severe cerebral palsy., Conclusion: In the presence of sonographic findings suggestive of fetal CMV infection, prompt investigation of amniotic fluid should follow even if maternal serology does not support recent maternal seroconversion., (Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.)