PURPOSE OF REVIEW:Globally, sequelae of congenital CMV (CCMV) impact an estimated 350 000 children born annually. In this review, we consider new evidence across primary, secondary and tertiary prevention approaches, and remaining evidence gaps. RECENT FINDINGS:Education on hygiene precautions can reduce risk of primary CMV acquisition in pregnancy, and may have a role in some settings in reducing CCMV cases resulting from nonprimary infection, but public and health worker knowledge and awareness remains low. Evidence that valaciclovir treatment can reduce CMV vertical transmission has led to renewed interest in antenatal CMV screening in some high-income countries over recent years, although there is a lack of recommendation in most guidelines and significant evidence gaps remain. Newborn CCMV screening has been adopted in some states/provinces in Canada/USA, with first results recently published. Newborn prognostic scoring systems are evolving, with potential for more effective targeting of newborn treatment and tertiary prevention of CCMV disease. SUMMARY:We make suggestions for clinical practice and research, particularly to address evidence gaps around: safety and effectiveness of antenatal CMV screening and antiviral prophylaxis; findings relating to detection of nonprimary infection in pregnancy; new prognostic neonatal scoring systems; and learning from follow-up of children born into state-wide universal CMV screening programmes.

Objective Congenital cytomegalovirus (cCMV) is the most common congenital infection globally, affecting approximately 0.5% of all live births in high income settings, with long-term sequelae affecting around a fifth of infected infants. Recently, interest in antenatal CMV screening has increased but current practices and impact are unclear. Our objective was to describe policy and practice around antenatal CMV screening, testing, and treatment in Europe, including the use of universal antenatal screening, in the context of the emerging evidence base for use of valaciclovir to reduce CMV vertical transmission (VT).Methods A web-based survey was distributed to healthcare professionals within antenatal services with knowledge of CMV testing/treatment practices, from 29 April 2024 to 24 July 2024. Responses from Europe were analyzed. Where multiple responses were submitted from the same healthcare service, the most complete response was kept for the analysis.Results We received responses from 73 centers in 21 countries in Europe, mostly 76% (55/72) from tertiary centers. Overall, 52% (38/73) had a CMV testing policy and 61% (23/38) reported that this had been introduced or significantly updated in the last 2 years. Half of respondents (53%, 39/73, from 11/21 countries) reported routine offer of CMV testing to pregnant woman at their center (universal antenatal screening), sometimes with gestational age limits, and mostly (67%, 26/39) on an “opt-out” basis. Universal antenatal CMV screening was more common among centers with formalized testing policies than those without (84% (32/38) vs. 20% (7/35) respectively, χ2 = 30.19, p < .01). For all sites, screening tests included CMV IgM and IgG, with 36% (14/39) offering IgG avidity, and 8% (3/39) using PCR. Of the 39 centers offering universal screening, the coverage was estimated to be >95% of pregnant women at half (18/39) of centers. Fifty-nine percent (23/39) of centers reported routinely offering repeat testing. Of 39 centers routinely offering testing, only 69% (27/39) gave advice on reducing CMV acquisition risk routinely to pregnant women. Medication was offered for prevention of CMV VT or tertiary prevention of cCMV disease at 82% (60/73) and 78% (56/72) of centers, respectively. Of 59 sites offering treatment for secondary and/or tertiary prevention and responding to a question on frequency of treatment monitoring, 93% (55/59) reported monitoring blood tests at least monthly. Forty-three percent of centers offering treatment lacked a formal procedure for reporting adverse drug reactions. Overall, 83% (58/70) respondents supported CMV testing (49 strongly, nine moderately), but 59% (41/70) identified at least one concern/risk.Conclusions This survey of antenatal CMV policies and practice at 73 centers in Europe highlights substantial variation in policies and practice, reflecting variation in national screening guidelines and the evolving evidence base around valaciclovir to reduce CMV VT risk. A recent opinion paper and statement have called for consideration of universal screening but also highlighted important evidence gaps around its implementation, risks, benefits, and cost-effectiveness. Responses to this survey suggested that valaciclovir is already quite widely used for prophylaxis of CMV VT in the context of maternal primary infection in early pregnancy, at participating sites. Our findings suggest that research to inform safe and equitable decisions around implementation of CMV testing and universal screening is urgently needed, in addition to epidemiological research to underpin screening decisions tailored to specific settings. Shared research priorities are needed to ensure testing and treatment are carried out in an evidence-based and equitable way.

BACKGROUND:Raltegravir is an HIV integrase strand transfer inhibitor recommended for use in pregnancy. The aim of this study was to assess risk of birth defects and other suboptimal outcomes after prenatal exposure to raltegravir. METHODS:We used pooled, prospectively collected individual patient data from studies in the European Pregnancy and Paediatric Infections Cohort Collaboration. Pregnancies with any prenatal exposure to raltegravir with outcomes in 2008-2020 were included. Birth defects were classified according to World Health Organization's International Classification of Diseases and EUROCAT criteria. Earliest prenatal exposure timing was classified as periconception [exposure at ≤6 completed gestational weeks (GWs)], later first trimester (T1) (exposure in T1 at >6 completed GWs), and second/third trimester (exposure at >12 completed GWs). RESULTS:A total of 1499 pregnancies across 9 cohorts were included. Where timing was available (n = 1449), earliest raltegravir exposure was in the periconception period for 505 (34.8%), later T1 in 65 (4.5%), and T2/T3 in 879 (60.7%). The overall prevalence of birth defects among live-born infants with prenatal raltegravir exposure was 3.9% (95% confidence interval: 2.9, 5.0) (1443/1466) (International Classification of Diseases), with no increased risk observed for those exposed in the periconception period ( P = 0.290). Among singleton live-born infants, 11.9% (160/1346) were born preterm, 11.3% (148/1307) low birthweight, and 8.6% (111/1291) small for gestational age, with no difference in outcomes observed by timing of raltegravir exposure. CONCLUSIONS:These findings add to the evidence base around safety of raltegravir use in pregnancy, although ongoing safety monitoring is needed to rule out risk of rare outcomes.

Objectives To describe the impact associated with congenital cytomegalovirus (cCMV) infection and experiences and perceptions of people with experience of CMV in pregnancy and families / caregivers of children diagnosed with cCMV, who responded to a UK National Screening Committee (UK NSC) public consultation on cCMV screening.Methods The public consultation was conducted in 2021-22 on a draft evidence review and was aimed at informing the UK NSC's decision on newborn screening for cCMV. Data were analysed using framework analysis: a subgroup of responses was inductively coded, codes were refined and initial themes identified, before targeted coding of the remainder of the data and identification of final themes and sub-themes.Results Of a total 155 responses, 125 (describing 128 pregnancy/child outcomes) contained information relevant to the coding framework and were included. Most (n = 109) described a live birth of a surviving child, of whom 90% (98/109) were living with symptoms or long-term sequelae of cCMV at the time of the response. Two main themes were identified: missed opportunities and emotional impacts attributed by respondents to not screening for cCMV. Many families described delays in their child's cCMV diagnosis, including due to healthcare professionals' lack of awareness of cCMV, and viewed newborn screening as a solution to avoid delays in diagnostic pathways. Diagnostic delays resulted in a lasting sense of injustice and unfairness due to possible missed opportunities to improve outcomes (e.g., through antiviral treatment or early therapies), as well as uncertainty and anxiety.Conclusions Responses were predominantly from parents and caregivers of children with cCMV who experienced long term disability. They highlight significant gaps in awareness, support and health care for affected children that need addressing, regardless of national screening policy decisions. These responses contribute to the literature on lived experiences of individuals and families affected by cCMV.

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5 years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.

We evaluated the effectiveness and safety of direct-acting antivirals in adolescents with hepatitis C (HCV)/HIV coinfection using pooled individual patient-level data from 5 European cohorts. Of 122 participants in follow-up from November 2013 to August 2021, 19 were treated <18 years of age; of 15 with HCV RNA available at/after 12 weeks post-treatment, all had sustained virologic response with acceptable safety. This evidence addresses an important gap in knowledge of treatment outcomes in adolescents with HCV/HIV coinfection in real-life settings.

Around 0.4% of pregnant women in England have chronic hepatitis B virus (HBV) infection and need services to prevent vertical transmission. In this national audit, sociodemographic, clinical and laboratory information was requested from all maternity units in England for hepatitis B surface antigen-positive women initiating antenatal care in 2014. We describe these women's characteristics and indicators of access to/uptake of healthcare. Of 2542 pregnancies in 2538 women, median maternal age was 31 [IQR 27, 35] years, 94% (1986/2109) were non-UK born (25% (228/923) having arrived into the UK <2 years previously) and 32% (794/2473) had ⩾2 previous live births. In 39%, English levels were basic/less than basic. Antenatal care was initiated at median 11.3 [IQR 9.6, 14] gestation weeks, and 'late' (⩾20 weeks) in 10% (251/2491). In 70% (1783/2533) of pregnancies, HBV had been previously diagnosed and 11.8% (288/2450) had ⩾1 marker of higher infectivity. Missed specialist appointments were reported in 18% (426/2339). Late antenatal care and/or missed specialist appointments were more common in pregnancies among women lacking basic English, arriving in the UK ⩽2 years previously, newly HBV diagnosed, aged <25 years and/or with ⩾2 previous live births. We show overlapping groups of pregnant women with chronic HBV vulnerable to delayed or incomplete care.

Background: Despite growing scientific knowledge of Zika virus (ZIKV) infection, questions remain regarding ZIKV infection in pregnancy and congenital ZIKV syndrome (CZS). Methods: The ZIKAction Paediatric Registry is an international registry of children with documented ZIKV exposure in utero and/or with confirmed or suspected CZS. Its aim is to characterize these children (i.e., clinical, radiological, neurodevelopmental features) and describe outcomes, longer-term sequelae and management through retrospective case note review. This analysis described the maternal and perinatal characteristics of children in the Registry’s Bahia arm, assessed their neuroimaging, ophthalmic, hearing and electroencephalography abnormalities by microcephaly classification and reported on hospitalisations. Children born in 2015-2018 and enrolled 2020-2021 in three public health facilities in Salvador were included. Results: Of 129 (57% female) children, 15 (11·6%) had laboratory-confirmed congenital ZIKV infection and 114 (88·4%) suspected CZS. At delivery, 15 (11·6%) were normocephalic, 30 (23·3%) moderately microcephalic, and 84 (65·1%) severely microcephalic. Median birth head circumference z-score was -3·51 [IQR, -4·69,-2·73]. During follow-up, all children had abnormal neuroimaging, 80·3% (94/117) abnormal electroencephalogram, 62·2% (77/120) ophthalmic abnormalities, and 27·4% (34/124) hearing impairment. Microcephaly classification was significantly associated with gestational age, and ophthalmological and electroencephalography abnormalities. Of 125 children with hospitalisation data, 52 (41·6%) had been hospitalised by most recent follow-up, at median age of 15·8 [4·0, 34·4] months; infections were the leading cause. Conclusion: Congenital ZIKV infection is an emerging disease with a varied and incompletely understood spectrum. Continued long-term follow-up is essential to understand longer-term prognosis and to inform future health and educational needs.

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants.

Background With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. Methods Data were collected from a prospective cohort of infants HIV-exposed aged 1–6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi’s Prevention of Mother-to-Child Transmission of HIV Programme (2014–2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P < 0.1. Results A total of 1,206 singleton CHEU and their mothers were enrolled and 563 completed the follow-up through 24 months of age. Moreover, 48% of CHEU were exposed to ART from conception, 40% from first/second trimester, and 12% from third trimester/postpartum. At enrollment, 12% of infants had low birthweight (LBW), 98% had been breastfed in past 7 days, and 57% were enrolled in an HIV care clinic. CHEU growth trajectories demonstrated cohort-wide growth faltering after the age of 12 months. Of 788 and 780 CHEU contributing to WAZ and LAZ multivariable models, respectively, there was no evidence of differences in mean WAZ or LAZ among those exposed from conception or first/second trimester vs. third trimester/postpartum and no evidence of a difference in WAZ or LAZ rate of change by timing of ART exposure (all interactions P > 1.0). Conclusion Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life.

Abstract Evidence suggests children HIV‐exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV‐exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother‐to‐Child HIV Transmission Programme after Option B+ implementation (2014–2018). Anthropometry was measured at enrolment (age 1–6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight‐for‐age (WAZ) and length‐for‐age (LAZ) z‐scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi‐variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82–6.17]), which was modified by co‐trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi‐faceted health risks, alongside maternal ART prescription, and follow‐up of mother‐child pairs.

BACKGROUND:The UK National Screening Committee currently recommends against antenatal screening for Hepatitis C virus (HCV) infection in England due to lack of HCV prevalence data and treatment licensed for use in pregnancy. We aimed to produce regional and national estimates of the number and proportion of livebirths to HCV seropositive women in England in 2013 and 2018. METHODS:A logistic regression model fitted in the Bayesian framework estimated probabilities of HCV seropositivity among 24,599 mothers delivering in the North Thames area of England in 2012 adjusted by maternal age and region of birth. These probabilities were applied to the underlying population structures of women delivering livebirths in England in 2013 and 2018 to estimate the number of livebirths to HCV seropositive women in these years nationally and by region. The Bayesian approach allowed the uncertainty associated with all estimates to be properly quantified. RESULTS:Nationally, the estimated number of livebirths to women seropositive for HCV for England was 464 (95% credible interval [CI] 300-692) in 2013 and 481 (95%CI 310-716) in 2018, or 70.0 (95%CI 45.0-104.1) per 100,000 and 76.9 (95%CI 49.5-114.4) per 100,000 in these years respectively. Regions with the highest estimated number of livebirths to HCV seropositive women in 2013 and 2018 included London with 118.5 and 124.4 and the South East with 67.0 and 74.0 per 100,000 livebirths. CONCLUSION:Few previous studies have investigated HCV among pregnant women in England. These findings complement and supplement existing research by providing national and regional estimates for the number of livebirths to HCV seropositive women in England. Bayesian modelling allows future national and regional estimates to be produced and the associated uncertainty to be properly quantified.

To determine the extent of exposure to Zika virus (ZIKV) and chikungunya virus (CHIKV) in Jamaica, we collected serum from 584 pregnant women during 2017–2019. We found that 15.6% had antibodies against ZIKV and 83.6% against CHIKV. These results indicate potential recirculation of ZIKV but not CHIKV in the near future.

Direct-acting antivirals (DAAs) have been approved for treating chronic hepatitis C virus (HCV) in children and adolescents. Although DAAs have been used in real-world settings for the treatment of HCV monoinfected adolescents, few reports of real-world use of DAAs in children and adolescents who are coinfected with human immunodeficiency virus (HIV) are available. We evaluated the real-world safety and effectiveness of DAAs in HIV/HCV coinfected adolescents from the Ukraine Paediatric HIV Cohort Study including all those for whom treatment outcomes were available by April 2021. Overall, 6 coinfected adolescents had received DAA treatment; 4 with sofosbuvir/ledipasvir (SOF/LDV), 1 with SOF/LDV+ribavirin, and 1 with SOF/daclatasvir. No patient discontinued treatment due to adverse events and no serious adverse events were reported. All 6 patients achieved sustained virologic response by 12 weeks after the end of therapy. DAA treatment was well tolerated and effective in adolescents with HIV/HCV coinfection in a real-world setting.

Background There is growing evidence of the benefits of mobile health technology, which include symptom tracking apps for research, surveillance, and prevention. No study has yet addressed arbovirus symptom tracking in pregnancy. Objective This study aimed to evaluate the use of a smartphone app (ZIKApp) to self-report arbovirus symptoms and pregnancy complications and to assess compliance with daily symptom diaries during pregnancy in a cohort of women in an arbovirus-endemic, subtropical, middle-income country (Jamaica). Methods Pregnant women aged ≥16 years, having a smartphone, and planning on giving birth at the recruiting center were enrolled between February 2020 and July 2020. ZIKApp comprised a daily symptom diary based on algorithms to identify potential episodes of arbovirus infection and pregnancy complications. Sociodemographic, epidemiological, and obstetric information was collected at enrollment, with additional review of medical records, and users’ perception was collected through an exit survey. Descriptive analyses and logistic regression analysis of possible factors associated with diary adherence were performed. Results Of the 173 women enrolled, 157 (90.8%) used ZIKApp for a median duration of 155 (IQR 127-173) days until pregnancy end, 6 (3.5%) used the app for <7 days, and 10 (5.8%) exited the study early. For each successive 30-day period from enrollment up to 150 days after enrollment, of these 157 women, 121 (77.1%) to 129 (82.2%) completed their daily symptom diary; 50 (31.8%) to 56 (35.7%) did so on the same day. Overall, 31.8% (50/157) of the women had good adherence to diary reporting (ie, they completed the task on the same day or 2 to 3 days later for ≥80% of the days enrolled). There were 3-fold higher odds of good adherence for participants aged >34 years versus those aged 25 to 29 years (adjusted odds ratio 3.14, 95% CI 1.10-8.98) and 2-fold higher odds for women with tertiary versus secondary education (adjusted odds ratio 2.26, 95% CI 1.06-4.83). Of the 161 women who ever made a diary entry, 5454 individual symptom reports were made (median 17 per woman; IQR 4-42; range 0-278); 9 (5.6%) women reported symptom combinations triggering a potential arbovirus episode (none had an adverse pregnancy outcome) and 55 (34.2%) reported painful uterine contractions or vaginal bleeding, mainly in the month before delivery. Overall, 51.8% (71/137) of the women rated the app as an excellent experience and were less likely to be poor diary adherers (P=.04) and 99.3% (138/139) reported that the app was easy to understand and use. Conclusions This pilot found a high adherence to ZIKApp. It demonstrated the feasibility and usability of the app in an arbovirus-endemic region, supporting its future development to contribute to surveillance and diagnosis of arbovirus infections in pregnancy and to optimize maternal care.