Conservative management of brain arteriovenous malformations: results of the prospective observation registry of a pragmatic trial.

OBJECTIVE: Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients. METHODS: TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding. RESULTS: From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1-2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7-1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2-1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4-13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1-7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4-7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9-3.6] per 100 patient-years; 2.0 [95% CI 1.3-2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6-2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1-8.9], p < 0.001), large (HR 2.6 [95% CI 1.1-6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2-5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1-4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7-4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0-4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0-3.2) per 100 patient-years. CONCLUSIONS: Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.

Reliability of study endpoint adjudication in a pragmatic trial on brain arteriovenous malformations.

BACKGROUND: The results of a clinical trial are given in terms of primary and secondary outcomes that are obtained for each patient. Just as an instrument should provide the same result when the same object is measured repeatedly, the agreement of the adjudication of a clinical outcome between various raters is fundamental to interpret study results. The reliability of the adjudication of study endpoints determined by examination of the electronic case report forms of a pragmatic trial has not previously been tested. METHODS: The electronic case report forms of 62/434 (14%) patients selected to be observed in a study on brain AVMs were independently examined twice (4 weeks apart) by 8 raters who judged whether each patient had reached the following study endpoints: (1) new intracranial hemorrhage related to AVM or to treatment; (2) new non-hemorrhagic neurological event; (3) increase in mRS ≥1; (4) serious adverse events (SAE). Inter and intra-rater reliability were assessed using Gwet's AC1 (κG) statistics, and correlations with mRS score using Cramer's V test. RESULTS: There was almost perfect agreement for intracranial hemorrhage (92% agreement; κG = 0.84 (95%CI: 0.76-0.93), and substantial agreement for SAEs (88% agreement; κG = 0.77 (95%CI: 0.67-0.86) and new non-hemorrhagic neurological event (80% agreement; κG = 0.61 (95%CI: 0.50-0.72). Most endpoints correlated (V = 0.21-0.57) with an increase in mRS of ≥1, an endpoint which was itself moderately reliable (76% agreement; κG = 0.54 (95%CI: 0.43-0.64). CONCLUSION: Study endpoints of a pragmatic trial were shown to be reliable. More studies on the reliability of pragmatic trial endpoints are needed.

Bilateral spheno-orbital meningiomas: surgical management, progression, and recurrence.

OBJECTIVE: Bilateral spheno-orbital meningiomas (bSOMs) are a rare entity among meningiomas. These tumors are benign and predominantly affect women. They represent 4% of spheno-orbital meningiomas (SOMs) and are poorly described in the literature. This study aimed to describe the characteristics, risk factors, evolution, and management of bSOMs. METHODS: Twenty patients with bSOMs were enrolled in a multicentric descriptive study including 15 neurosurgical departments. RESULTS: In this study, the authors found that bSOMs affected exclusively women, with a mean age of 50 years. Approximately 65% of patients were on progestin therapy. The mean follow-up in this series was 55 months. Clinically, visual symptoms were predominant: proptosis was present in 17 of 20 patients (85%; 7 unilateral, 10 bilateral), and a decrease in visual acuity was observed in 11 of 20 patients (55%; 6/10 to 9/10 in 6 patients, 3/10 to 5/10 in 1 patient, and < 3/10 in 4 patients). Contrary to unilateral SOMs, the authors identified that intracranial hypertension was a common presentation (25%) of bSOMs. Surgical management with gross-total resection was the gold standard treatment. Recurrences only occurred following subtotal resection in 36% to 60% of patients, with a median time of 50 to 54 months after surgery. Visual improvement or stability was observed in 75% of cases postoperatively. Progesterone receptor expression levels were 70% to 100% in 10 of 11 (91%) cases. CONCLUSIONS: Bilateral SOMs are usually found in female patients and are strongly associated with hormone replacement therapy. Early surgical management with gross-total resection is the most effective treatment in terms of recurrence and improves visual acuity. Given the slow progressive nature of bSOMs and their time to recurrence, which can be up to 10 years, long-term follow-up of patients is essential.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Pregnancy and infant outcomes by trimester of SARS-CoV-2 infection in pregnancy-SET-NET, 22 jurisdictions, January 25, 2020-December 31, 2020.

OBJECTIVES: We describe clinical characteristics, pregnancy, and infant outcomes in pregnant people with laboratory-confirmed SARS-CoV-2 infection by trimester of infection. STUDY DESIGN: We analyzed data from the Surveillance for Emerging Threats to Mothers and Babies Network and included people with infection in 2020, with known timing of infection and pregnancy outcome. Outcomes are described by trimester of infection. Pregnancy outcomes included live birth and pregnancy loss (<20 weeks and ≥20 weeks gestation). Infant outcomes included preterm birth (<37 weeks gestation), small for gestational age, birth defects, and neonatal intensive care unit admission. Adjusted prevalence ratios (aPR) were calculated for pregnancy and selected infant outcomes by trimester of infection, controlling for demographics. RESULTS: Of 35,200 people included in this analysis, 50.8% of pregnant people had infection in the third trimester, 30.8% in the second, and 18.3% in the first. Third trimester infection was associated with a higher frequency of preterm birth compared to first or second trimester infection combined (17.8% vs. 11.8%; aPR 1.44 95% CI: 1.35-1.54). Prevalence of birth defects was 553.4/10,000 live births, with no difference by trimester of infection. CONCLUSIONS: There were no signals for increased birth defects among infants in this population relative to national baseline estimates, regardless of timing of infection. However, the prevalence of preterm birth in people with SARS-CoV-2 infection in pregnancy in our analysis was higher relative to national baseline data (10.0-10.2%), particularly among people with third trimester infection. Consequences of COVID-19 during pregnancy support recommended COVID-19 prevention strategies, including vaccination.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Six-Month Outcomes of Infants Born to People With SARS-CoV-2 in Pregnancy.

OBJECTIVES: To assess the 6-month incidence of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, postnatal care, hospitalization, and mortality among infants born to people with laboratory-confirmed SARS-CoV-2 infection during pregnancy by timing of maternal infection. METHODS: Using a cohort of liveborn infants from pregnancies with SARS-CoV-2 infections in the year 2020 from 10 United States jurisdictions in the Surveillance for Emerging Threats to Mother and Babies Network, we describe weighted estimates of infant outcomes from birth through 6 months of age from electronic health and laboratory records. RESULTS: Of 6601 exposed infants with laboratory information through 6 months of age, 1.0% (95% confidence interval: 0.8-1.1) tested positive, 19.1% (17.5-20.6) tested negative, and 80.0% (78.4-81.6) were not known to be tested for SARS-CoV-2. Among those ≤14 days of age, SARS-CoV-2 infection occurred only with maternal infection ≤14 days before delivery. Of 3967 infants with medical record abstraction, breastmilk feeding initiation was lower when maternal infection occurred ≤14 days before delivery compared with >14 days (77.6% [72.5-82.6] versus 88.3% [84.7-92.0]). Six-month all-cause hospitalization was 4.1% (2.0-6.2). All-cause mortality was higher among infants born to people with infection ≤14 days (1.0% [0.4-1.6]) than >14 days (0.3% [0.1-0.5]) before delivery. CONCLUSIONS: Results are reassuring, with low incidences of most health outcomes examined. Incidence of infant SARS-CoV-2, breastmilk feeding initiation, and all-cause mortality differed by timing of maternal infection. Strategies to prevent infections and support pregnant people with coronavirus disease 2019 may improve infant outcomes.

Preterm birth among pregnant persons with severe acute respiratory syndrome Coronavirus 2 infection.

OBJECTIVE: We examined the relationship between trimester of SARS-CoV-2 infection, illness severity, and risk for preterm birth. STUDY DESIGN: We analyzed data for 6336 pregnant persons with SARS-CoV-2 infection in 2020 in the United States. Risk ratios for preterm birth were calculated for illness severity, trimester of infection, and illness severity stratified by trimester of infection adjusted for age, selected underlying medical conditions, and pregnancy complications. RESULT: Pregnant persons with critical COVID-19 or asymptomatic infection, compared to mild COVID-19, in the second or third trimester were at increased risk of preterm birth. Pregnant persons with moderate-to-severe COVID-19 did not show increased risk of preterm birth in any trimester. CONCLUSION: Critical COVID-19 in the second or third trimester was associated with increased risk of preterm birth. This finding can be used to guide prevention strategies, including vaccination, and inform clinical practices for pregnant persons.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

SARS-CoV-2 infections among neonates born to pregnant people with SARS-CoV-2 infection: Maternal, pregnancy and birth characteristics.

BACKGROUND: Multiple reports have described neonatal SARS-CoV-2 infection, including likely in utero transmission and early postnatal infection, but published estimates of neonatal infection range by geography and design type. OBJECTIVES: To describe maternal, pregnancy and neonatal characteristics among neonates born to people with SARS-CoV-2 infection during pregnancy by neonatal SARS-CoV-2 testing results. METHODS: Using aggregated data from the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) describing infections from 20 January 2020 to 31 December 2020, we identified neonates who were (1) born to people who were SARS-CoV-2 positive by RT-PCR at any time during their pregnancy, and (2) tested for SARS-CoV-2 by RT-PCR during the birth hospitalisation. RESULTS: Among 28,771 neonates born to people with SARS-CoV-2 infection during pregnancy, 3816 (13%) underwent PCR testing and 138 neonates (3.6%) were PCR positive. Ninety-four per cent of neonates testing positive were born to people with infection identified ≤14 days of delivery. Neonatal SARS-CoV-2 infection was more frequent among neonates born preterm (5.7%) compared to term (3.4%). Neonates testing positive were born to both symptomatic and asymptomatic pregnant people. CONCLUSIONS: Jurisdictions reported SARS-CoV-2 RT-PCR results for only 13% of neonates known to be born to people with SARS-CoV-2 infection during pregnancy. These results provide evidence of neonatal infection identified through multi-state systematic surveillance data collection and describe characteristics of neonates with SARS-CoV-2 infection. While perinatal SARS-CoV-2 infection was uncommon among tested neonates born to people with SARS-CoV-2 infection during pregnancy, nearly all cases of tested neonatal infection occurred in pregnant people infected around the time of delivery and was more frequent among neonates born preterm. These findings support the recommendation for neonatal SARS-CoV-2 RT-PCR testing, especially for people with acute infection around the time of delivery.

Identifying possible inaccuracy in reported birth head circumference measurements among infants in the US Zika Pregnancy and Infant Registry.

BACKGROUND: The US Zika Pregnancy and Infant Registry (USZPIR) monitors infants born to mothers with confirmed or possible Zika virus infection during pregnancy. The surveillance case definition for Zika-associated birth defects includes microcephaly based on head circumference (HC). METHODS: We assessed birth and follow-up data from infants with birth HC measurements <3rd percentile and birthweight ≥10th percentile to determine possible misclassification of microcephaly. We developed a schema informed by literature review and expert opinion to identify possible HC measurement inaccuracy using HC growth velocity and longitudinal HC measurements between 2 and 12 months of age. Two or more HC measurements were required for assessment. Inaccuracy in birth HC measurement was suspected if growth velocity was >3 cm/month in the first 3 months or HC was consistently >25th percentile during follow-up. RESULTS: Of 6,799 liveborn infants in USZPIR, 351 (5.2%) had Zika-associated birth defects, of which 111 had birth HC measurements <3rd percentile and birthweight ≥10th percentile. Of 84/111 infants with sufficient follow-up, 38/84 (45%) were classified as having possible inaccuracy of birth HC measurement, 19/84 (23%) had HC ≥3rd percentile on follow-up without meeting criteria for possible inaccuracy, and 27/84 (32%) had continued HC <3rd percentile. After excluding possible inaccuracies, the proportion of infants with Zika-associated birth defects including microcephaly decreased from 5.2% to 4.6%. CONCLUSIONS: About one-third of infants in USZPIR with Zika-associated birth defects had only microcephaly, but indications of possible measurement inaccuracy were common. Implementation of this schema in longitudinal studies can reduce misclassification of microcephaly.

Risk Factors for Illness Severity Among Pregnant Women With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 Infection-Surveillance for Emerging Threats to Mothers and Babies Network, 22 State, Local, and Territorial Health Departments, 29 March 2020-5 March 2021.

BACKGROUND: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during 29 March 2020-5 March 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. RESULTS: Among 7950 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 25 years and older, healthcare occupation, prepregnancy obesity, chronic lung disease, chronic hypertension, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. CONCLUSIONS: Older age and having underlying medical conditions were associated with increased risk of moderate-to-severe or critical COVID-19 illness among pregnant women. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and can inform targeted public health messaging.

A Preparedness Model for Mother-Baby Linked Longitudinal Surveillance for Emerging Threats.

INTRODUCTION: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a 5-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). OBJECTIVES: The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants. METHODS: Mother-baby pairs are identified through prospective identification during pregnancy and/or identification of an infant with retrospective linking to maternal information. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting). RESULTS: Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing). DISCUSSION: SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has already demonstrated rapid adaptation to COVID-19. This innovative approach leverages existing data sources and rapidly collects data and informs clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.

Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection - U.S. Territories and Freely Associated States, 2018.

INTRODUCTION: Zika virus infection during pregnancy causes serious birth defects and might be associated with neurodevelopmental abnormalities in children. Early identification of and intervention for neurodevelopmental problems can improve cognitive, social, and behavioral functioning. METHODS: Pregnancies with laboratory evidence of confirmed or possible Zika virus infection and infants resulting from these pregnancies are included in the U.S. Zika Pregnancy and Infant Registry (USZPIR) and followed through active surveillance methods. This report includes data on children aged ≥1 year born in U.S. territories and freely associated states. Receipt of reported follow-up care was assessed, and data were reviewed to identify Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection. RESULTS: Among 1,450 children of mothers with laboratory evidence of confirmed or possible Zika virus infection during pregnancy and with reported follow-up care, 76% had developmental screening or evaluation, 60% had postnatal neuroimaging, 48% had automated auditory brainstem response-based hearing screen or evaluation, and 36% had an ophthalmologic evaluation. Among evaluated children, 6% had at least one Zika-associated birth defect identified, 9% had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection identified, and 1% had both. CONCLUSION: One in seven evaluated children had a Zika-associated birth defect, a neurodevelopmental abnormality possibly associated with congenital Zika virus infection, or both reported to the USZPIR. Given that most children did not have evidence of all recommended evaluations, additional anomalies might not have been identified. Careful monitoring and evaluation of children born to mothers with evidence of Zika virus infection during pregnancy is essential for ensuring early detection of possible disabilities and early referral to intervention services.

Pregnancy Outcomes After Maternal Zika Virus Infection During Pregnancy - U.S. Territories, January 1, 2016-April 25, 2017.

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territories† with local transmission of Zika virus reported 2,549 completed pregnancies§ (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection¶ (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).