Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Moore CA[original query] |
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Public health priorities for gastroschisis: Summary of a meeting sponsored by the Centers for Disease Control and Prevention and the March of Dimes
Tepper NK , Chowdhury J , Moore CA , Werler MM , Mishkin K , Reefhuis J . Birth Defects Res 2024 116 (1) e2299 BACKGROUND: Gastroschisis has increased worldwide over several decades; however, there are significant gaps in understanding risk factors for development of the defect, particularly those that might be modifiable. Despite advances in survival, little is known about longer-term outcomes for affected individuals. METHODS: On April 27- and 28, 2023, the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention (CDC) and March of Dimes sponsored a meeting entitled "Public Health Priorities for Gastroschisis". The meeting goals were to review current knowledge on gastroschisis, discuss research gaps, and identify future priorities for public health surveillance, research, and action related to gastroschisis. Meeting participants encompassed a broad range of expertise and experience, including public health, clinical care of individuals with gastroschisis, affected individuals and families, and representatives from professional organizations and federal agencies. RESULTS: Several goals were identified for future public health surveillance and research, including focused theory-driven research on risk factors and increased study of longer-term effects of gastroschisis through improved surveillance. Certain public health actions were identified, that which could improve the care of affected individuals, including increased education of providers and enhanced resources for patients and families. CONCLUSIONS: These efforts may lead to an improved understanding of pathogenesis, risk factors, and outcomes and to improved care throughout the lifespan. |
Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021
Namale-Matovu J , Kusolo R , Serunjogi R , Barlow-Mosha L , Mumpe-Mwanja D , Niombi N , Kalibbala D , Williamson D , Valencia D , Moore CA , Mwambi K , Nelson LJ , Namukanja-Mayambala PM , Williams JL , Mai CT , Qi YP , Musoke P . BMC Med Educ 2023 23 (1) 766 BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development. |
Outcomes up to age 36 months after congenital Zika virus infection-U.S. states
Neelam V , Woodworth KR , Chang DJ , Roth NM , Reynolds MR , Akosa A , Carr CP , Anderson KN , Mulkey SB , DeBiasi RL , Biddle C , Lee EH , Elmore AL , Scotland SJ , Sowunmi S , Longcore ND , Ahmed M , Langlois PH , Khuwaja S , Browne SE , Lind L , Shim K , Gosciminski M , Blumenfeld R , Khuntia S , Halai UA , Locklear A , Chan M , Willabus T , Tonzel J , Marzec NS , Barreto NA , Sanchez C , Fornoff J , Hale S , Nance A , Iguchi L , Adibhatla SN , Potts E , Schiffman E , Raman D , McDonald MF , Stricklin B , Ludwig E , Denson L , Contreras D , Romitti PA , Ferrell E , Marx M , Signs K , Cook A , Leedom VO , Beauregard S , Orantes LC , Cronquist L , Roush L , Godfred-Cato S , Gilboa SM , Meaney-Delman D , Honein MA , Moore CA , Tong VT . Pediatr Res 2023 BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models. |
Notes from the field: Autism spectrum disorder among children with laboratory evidence of prenatal Zika virus exposure - Puerto Rico, 2023
Roth NM , Delgado-López C , Wiggins LD , Muñoz NN , Mulkey SB , Nieves-Ferrer L , Woodworth KR , Rosario GM , Huertas MM , Moore CA , Tong VT , Gilboa SM , Valencia-Prado M . MMWR Morb Mortal Wkly Rep 2023 72 (29) 802-804 Infection during pregnancy with Zika virus, a mosquitoborne flavivirus, can cause birth defects and neurodevelopmental abnormalities (1). Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by social and communication impairment and restricted or repetitive patterns of behavior or interests (2); possible associations between antenatal exposure to a limited number of viruses and ASD have been observed (2). The U.S. Zika Pregnancy and Infant Registry (USZPIR)* monitors children born during January 1, 2016–March 31, 2018, to women with laboratory evidence of Zika virus infection during pregnancy. This report used data from USZPIR and the Puerto Rico Autism Registry† to estimate the prevalence of ASD diagnoses among children with possible prenatal Zika virus exposure and to describe prenatal characteristics and other outcomes by ASD diagnosis status. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ |
Changes in spina bifida lesion level after folic acid fortification in the US
Mai CT , Evans J , Alverson CJ , Yue X , Flood T , Arnold K , Nestoridi E , Denson L , Adisa O , Moore CA , Nance A , Zielke K , Rice S , Shan X , Dean JH , Ethen M , Hansen B , Isenburg J , Kirby RS . Obstet Gynecol Surv 2023 78 (4) 189-191 following which a substantial decline in neural tube defects at birth occurred. Studies also have suggested that lesion levels in cases of spina bifida are directly affected by folic acid fortification. Locations of such lesions contribute to outcome and prognosis of the condition. When compared with sacral and lower lumbar lesions, the greatest risks of disability and mortality are associated with cervical, thoracic, and high lumbar lesions. Individuals with thoracic or high lumbar lesions require a wheelchair and orthosis in adulthood for ambulation 70% to 99% of the time. As lesion levels therefore determine function and overall quality of life, assessment of whether folic acid fortification significantly impacts lesion levels is important. This study aimed to examine patterns of lesion levels in spina bifida following mandatory folic acid fortification in the United States. | | A call was issued by the National Birth Defects Prevention Network for State Birth Defects Programs' spina bifida lesion data before and after fortification mandate. To be eligible, programs needed to provide verbatim medical record text descriptions of spina bifida diagnoses. The 6 participating programs were from the states of Arizona, California (covering 8 counties), Oklahoma, South Carolina, Utah, and metropolitan Atlanta (Georgia). Birth years examined included the prefortification years of 1992–1996 and the postfortification period of 1999–2016. Central processing and analysis occurred as each program provided case-level data (deidentified) based on the exclusion/inclusion criteria to the Centers for Disease Control and Prevention. Medical and record text description of the spina bifida diagnosis and codes were the basis of case information, using the International Classification of Diseases, Ninth Edition, Clinical Modification or the Centers for Disease Control and Prevention and Prevention/British Pediatric Association coding system. Types of spina bifida included in the study were spinal rachischisis, myelomeningocele/meningomyelocele, meningocele, and spina bifida not otherwise specified. Cases excluded were cranial lesions, lipomyelomeningocele/lipomeningomyelocele, dysraphism related to split cord malformations, and spina bifida occulta. | | Lesion-level information was provided based on the highest lesion using nonradiographic clinical assessment. Classification of severe upper-level lesions included cervical or thoracic lesion-level cases, whereas lower-level lesions included cases with lumbar or sacral. The study defined open lesion as leaking spinal fluid or membrane covered only, whereas closed lesions were defined as having intact-skin covering and lacking fluid leakage. Spina bifida cases were considered isolated when no other anomalies related to the primary cause of abnormal neural tube closure were present (nor were secondary to the neurologic complications caused by it). Examining associations between fortification period and the outcomes (lesion level and spina bifida) occurred using the generalized estimating approach to logistic (case severity analyses) and log-linear (PR analyses) regression, which accounted for clustering of cases by state. | | From a total of 7,816,062 live births, 2593 cases of spina bifida met the case inclusion criteria. Overall, 573 cases were included in the prefortification period (birth prevalence of 4.07 per 10,000 live births), and 2020 cases were included in the postfortification period (birth prevalence of 3.15 per 10,000 live births). Overall, 80.2% of cases resulted in live births, and most cases of spina bifida involved lower-level lesions (81.3%). Most lesions were lumbar, and the proportions prefortification and postfortification were 61.4% and 72.0%, respectively, with a higher proportion of lumbar lesions seen in the postfortification period. The odds of upper-level to lower-level lesions decreased by 70% after fortification. The spina bifida live birth prevalence decreased significantly and remained consistently low throughout the early, mid, and recent postfortification periods. The study found a 72% decrease overall in prevalence of severe, upper-level lesions following mandatory folic acid fortification in the United States. | | The limitations of the study include the shortcomings of relying on diagnostic codes, the difficulty of coding lesion level using the International Classification of Diseases, Ninth Edition, Clinical Modification coding scheme, the lack of recorded functional outcome for children in medical records (indirect indicators of severity), the lack of preconception and prenatal folic acid data, and the possible variation of case ascertainment within programs contributing studies. A major study strength is its potential to address additional important questions regarding epidemiology and spina bifida. The classification of spinal defects is complex, and this study adds to the limited distribution data that exist for prefortification and postfortification subtypes. | | The study concluded that the overall prevalence of severe upper-level lesions in spina bifida cases experienced a steep reduction following mandatory folic acid fortification institution within the United States, whereas no change in the prevalence of less severe lower-level lesions took place. Additional examinations are warranted to better understand the magnitude and mechanism of spina bifida severity in relation to folic acid intake. |
Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.
Sok P , Sabo A , Almli LM , Jenkins MM , Nembhard WN , Agopian AJ , Bamshad MJ , Blue EE , Brody LC , Brown AL , Browne ML , Canfield MA , Carmichael SL , Chong JX , Dugan-Perez S , Feldkamp ML , Finnell RH , Gibbs RA , Kay DM , Lei Y , Meng Q , Moore CA , Mullikin JC , Muzny D , Olshan AF , Pangilinan F , Reefhuis J , Romitti PA , Schraw JM , Shaw GM , Werler MM , Harpavat S , Lupo PJ . Am J Med Genet A 2023 191 (6) 1546-1556 The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex. |
Zika virus as a cause of birth defects: Were the teratogenic effects of Zika virus missed for decades?
Gilbert RK , Petersen LR , Honein MA , Moore CA , Rasmussen SA . Birth Defects Res 2022 115 (3) 265-274 Zika virus (ZIKV) was identified as a teratogen in 2016 when an increase in severe microcephaly and other brain defects was observed in fetuses and newborns following outbreaks in French Polynesia (2013-2014) and Brazil (2015-2016) and among travelers to other countries experiencing outbreaks. Some have questioned why ZIKV was not recognized as a teratogen before these outbreaks: whether novel genetic changes in ZIKV had increased its teratogenicity or whether its association with birth defects had previously been undetected. Here we examine the evidence for these two possibilities. We describe evidence for specific mutations that arose before the French Polynesia outbreak that might have increased ZIKV teratogenicity. We also present information on children born with findings consistent with congenital Zika syndrome (CZS) as early as 2009 and epidemiological evidence that suggests increases in CZS-type birth defects before 2013. We also explore reasons why a link between ZIKV and birth defects might have been missed, including issues with surveillance of ZIKV infections and of birth defects, challenges to ZIKV diagnostic testing, and the susceptibility of different populations to ZIKV infection at the time of pregnancy. Although it is not possible to prove definitively that ZIKV had teratogenic properties before 2013, several pieces of evidence support the hypothesis that its teratogenicity had been missed in the past. These findings emphasize the need for further investments in global surveillance for emerging infections and for birth defects so that infectious teratogens can be identified more expeditiously in the future. |
Prevalence of individual brain and eye defects potentially related to Zika virus in pregnancy in 22U.S. states and territories, January 2016 to June 2017
Delaney A , Olson SM , Roth NM , Cragan JD , Godfred-Cato S , Smoots AN , Fornoff J , Nestoridi E , Eckert V , Forkner A , Stolz A , Crawford K , Cho SJ , Elmore A , Langlois P , Nance A , Denson L , Forestieri N , Leedom VO , Tran T , Valencia-Prado M , Romitti P , Barton JE , St John K , Mann S , Orantes L , DeWilde L , Tong VT , Gilboa SM , Moore CA , Honein MA . Birth Defects Res 2022 114 (14) 805-811 During the Centers for Disease Control and Prevention's Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016 to June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared with areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January-March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR = 12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3 [4.7, 18.4]), and cerebral/cortical atrophy (6.7 [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy. |
Changes in spina bifida lesion level after folic acid fortification in the United States
Mai CT , Evans J , Alverson CJ , Yue X , Flood T , Arnold K , Nestoridi E , Denson L , Adisa O , Moore CA , Nance A , Zielke K , Rice S , Shan X , Dean JH , Ethen M , Hansen B , Isenburg J , Kirby RS . J Pediatr 2022 249 59-66 e1 OBJECTIVE: To assess whether the severity of cases of spina bifida changed after mandatory folic acid fortification in the United States. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (pre-fortification) and 1999-2016 (post-fortification); programs contributed varying years of data. Case information included both medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing pre- with post-fortification periods, adjusted odds ratios (aOR) for case severity [upper-level (cervical, thoracic) to lower-level (lumbar, sacral) lesion cases] and prevalence ratios (PR) were estimated. RESULTS: A total of 2,593 cases of spina bifida (7,816,062 live births) met inclusion criteria, with 573 and 2,020 cases from the pre- and post-fortification periods respectively. Case severity decreased 70% (aOR: 0.30; 95% confidence interval [CI] 0.26, 0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic white mothers. Overall spina bifida prevalence declined 23% (PR=0.77, 95% CI=0.71, 0.85), with similar reduction seen across early, mid, and recent post-fortification periods. A statistically significant decrease in upper-level lesions occurred in the post-fortification compared with pre-fortification periods (PR=0.28, 95% CI=0.22, 0.34), while prevalence of lower-level lesions remained relatively similar (PR: 0.94, 95% CI: 0.84, 1.05). CONCLUSIONS: Severity of cases of spina bifida decreased after mandatory folic acid fortification in the United States. Further examination is warranted to understand better the potential effect of folic acid on spina bifida severity. |
Identifying possible inaccuracy in reported birth head circumference measurements among infants in the US Zika Pregnancy and Infant Registry
Roth NM , Woodworth KR , Godfred-Cato S , Delaney AM , Olson SM , Nahabedian JF3rd , Reynolds MR , Jones AM , Neelam V , Valencia-Prado M , Delgado-López C , Lee EH , Ellis EM , Lake-Burger H , Tonzel JL , Higgins CA , Chan RL , Tong VT , Gilboa SM , Cragan JD , Honein MA , Moore CA . Birth Defects Res 2022 114 (8) 314-318 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. |
Mortality from congenital Zika syndrome - nationwide cohort study in Brazil
Paixao ES , Cardim LL , Costa MCN , Brickley EB , de Carvalho-Sauer RCO , Carmo EH , Andrade RFS , Rodrigues MS , Veiga RV , Costa LC , Moore CA , França GVA , Smeeth L , Rodrigues LC , Barreto ML , Teixeira MG . N Engl J Med 2022 386 (8) 757-767 BACKGROUND: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. METHODS: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. RESULTS: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. CONCLUSIONS: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.). |
Periconceptional folic acid use prevents both rare and common neural tube defects in China
Zhou Y , Crider KS , Yeung LF , Rose CE , Li Z , Berry RJ , Li S , Moore CA . Birth Defects Res 2022 114 184-196 BACKGROUND: Neural tube defects (NTDs) encompass a variety of distinct types. We assessed if the preventive effect of folic acid (FA) varied by NTD type and infant sex. METHODS: We examined all pregnancies with NTD status confirmation from a pregnancy-monitoring system in selected locations in northern and southern regions of China between 1993 and 1996. Women who took 400 μg of FA daily during 42 days after last menstrual period were considered FA users. We analyzed NTD prevalence by FA use status, NTD type, geographic region, and infant sex. RESULTS: Among 626,042 pregnancies, 700 were affected by an NTD. Among FA nonusers, 65 pregnancies (8.8 per 10,000) in the north and 51 pregnancies (1.2 per 10,000) in the south were affected by one of the two rare NTDs, that is, craniorachischisis, iniencephaly. FA use prevented occurrence of these two rare NTDs and reduced the prevalence of spina bifida (SB) by 78% (from 17.9 to 3.9 per 10,000) in the north and 51% (from 2.4 to 1.2 per 10,000) in the south. Among FA users, SB prevalence, including SB with high lesion level, was significantly reduced in both geographic regions. FA use reduced prevalence of anencephaly and encephalocele by 85% and 50%, respectively in the north, while it did not reduce the prevalence of these two NTDs in the south. There was a greater reduction in NTD prevalence in female than in male infants and fetuses. CONCLUSIONS: This is the first study to show that FA prevents the entire spectrum of NTD types. |
Zika-associated birth defects reported in pregnancies with laboratory evidence of confirmed or possible Zika virus infection - U.S. Zika Pregnancy and Infant Registry, December 1, 2015-March 31, 2018
Roth NM , Reynolds MR , Lewis EL , Woodworth KR , Godfred-Cato S , Delaney A , Akosa A , Valencia-Prado M , Lash M , Elmore A , Langlois P , Khuwaja S , Tufa A , Ellis EM , Nestoridi E , Lyu C , Longcore ND , Piccardi M , Lind L , Starr S , Johnson L , Browne SE , Gosciminski M , Velasco PE , Johnson-Clarke F , Locklear A , Chan M , Fornoff J , Toews KE , Tonzel J , Marzec NS , Hale S , Nance AE , Willabus T , Contreras D , Adibhatla SN , Iguchi L , Potts E , Schiffman E , Lolley K , Stricklin B , Ludwig E , Garstang H , Marx M , Ferrell E , Moreno-Gorrin C , Signs K , Romitti P , Leedom V , Martin B , Castrodale L , Cook A , Fredette C , Denson L , Cronquist L , Nahabedian JF3rd , Shinde N , Polen K , Gilboa SM , Martin SW , Cragan JD , Meaney-Delman D , Honein MA , Tong VT , Moore CA . MMWR Morb Mortal Wkly Rep 2022 71 (3) 73-79 Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance. |
Medicaid healthcare expenditures for infants with birth defects potentially related to Zika virus infection in North Carolina, 2011-2016
Bergman K , Forestieri NE , Di Bona VL , Grosse SD , Moore CA . Birth Defects Res 2022 114 (2) 80-89 BACKGROUND: In 2016, Zika virus (ZIKV) was recognized as a human teratogen. North Carolina (NC) had no local transmission of ZIKV but infants with relevant birth defects, including severe brain anomalies, microcephaly, and eye abnormalities, require specialized care and services, the costs of which have not yet been quantified. The objective of this study is to examine NC Medicaid healthcare expenditures for infants with defects potentially related to ZIKV compared to infants with no reported defects. METHODS: Data sources for this retrospective cohort study include NC birth certificates, Birth Defects Monitoring Program data, and Medicaid enrollment and paid claims files. Infants with relevant defects were identified and expenditure ratios were calculated to compare distributions of estimated expenditures during the first year of life for infants with relevant defects and infants with no reported defects. RESULTS: This analysis included 551 infants with relevant defects and 365,318 infants with no reported defects born 2011-2016. Mean total expenditure per infant with defects was $69,244 (median $30,544) for the first year. The ratio of these expenditures relative to infants with no reported defects was 14.5. Expenditures for infants with select brain anomalies were greater than those for infants with select eye abnormalities only. CONCLUSIONS: Infants with defects potentially related to ZIKV had substantially higher Medicaid expenditures than infants with no reported defects. These results may be informative in the event of a future outbreak and are a resource for program planning related to care for infants in NC. |
Prevalence of neural tube defects, maternal HIV status, and antiretroviral therapy from a hospital-based birth defect surveillance in Kampala, Uganda
Barlow-Mosha L , Serunjogi R , Kalibbala D , Mumpe-Mwanja D , Williamson D , Valencia D , Tinker SC , Matovu JN , Moore CA , Adler MR , Nelson L , Nankunda J , Nabunya E , Birabwa-Male D , Musoke P . Birth Defects Res 2021 114 95-104 BACKGROUND: The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited. METHODS: Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs). RESULTS: A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]). CONCLUSION: The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated. |
Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016-2018
Mercado-Reyes M , Gilboa SM , Valencia D , Daza M , Tong VT , Galang RR , Winfield CM , Godfred-Cato S , Benavides M , Villanueva JM , Thomas JD , Daniels J , Zaki S , Reagan-Steiner S , Bhatnagar J , Schiffer J , Steward-Clark E , Ricaldi JN , Osorio J , Sancken CL , Pardo L , Tinker SC , Anderson KN , Rico A , Burkel VK , Hojnacki J , Delahoy MJ , González M , Osorio MB , Moore CA , Honein MA , Ospina Martinez ML . Trop Med Infect Dis 2021 6 (4) Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy. |
Clinical and neurodevelopmental outcomes based on brain imaging studies in a Colombian cohort of children with probable antenatal Zika virus exposure
Daza M , Mercado M , Moore CA , Valencia D , Lengua MF , Newton S , Rodríguez B , Tong VT , Acevedo P , Gilboa SM , Ospina ML , Mulkey SB . Birth Defects Res 2021 113 (18) 1299-1312 BACKGROUND: Our aim was to describe the neuroimaging and clinical evaluations of children with antenatal Zika-virus (ZIKV) exposure. METHODS: The Colombian National Institute of Health performed serial clinical evaluations of children with probable antenatal ZIKV exposure (i.e., born to ZIKV symptomatic mothers or born with birth defects compatible with ZIKV infection, regardless of laboratory results) over 2 years that included head circumference (HC), eye examination, and neurodevelopmental assessments. Clinical neuroimaging studies (head computed tomography and/or brain magnetic resonance imaging) were analyzed for abnormalities, two-dimensional measurements were made of the right and left frontal and occipital cortical thickness. Two abnormal patterns were defined: Pattern 1 (sum of four areas of cortex <6 cm) and Pattern 2 (sum of four areas of cortex ≥6 cm and < 10 cm). RESULTS: Thirty-one children had a neuroimaging study; in 24, cortical thickness was measured. The median age at the first visit was 8 (range: 6-9) months and 22 (range: 19-42) months at the last evaluation. In the 24 cases with cortical measurements, three were normal, 12 were in Pattern 1, and nine were in Pattern 2. Children within Pattern 1 had lower mean HC at birth and in follow-up (both p < .05) and a higher frequency of structural eye abnormalities (p < .01). A trend towards poorer neuromotor development was seen in Pattern 1, although not statistically significant (p = .06). CONCLUSION: Brain imaging classification based on cortical measurements correlate with ophthalmologic abnormalities and HC. Cortical thickness may be a marker for clinical outcomes in children with congenital ZIKV infection. |
Clinical phenotype in infants with negative Zika virus immunoglobulin M testing born to mothers with confirmed Zika virus infection during pregnancy
Godfred-Cato S , Newton S , Adams L , Valencia-Prado M , Lake-Burger H , Morrison A , Jones AM , Olson SM , Roth NM , Tong VT , Gilboa SM , Meaney Delman D , Honein MA , Staples JE , Moore CA . Birth Defects Res 2021 113 (17) 1267-1274 BACKGROUND: Recommended testing for both infants with Zika-associated birth defects (i.e., microcephaly and selected brain or eye anomalies) and infants without birth defects whose mothers had laboratory evidence of possible Zika virus (ZIKV) infection during pregnancy includes nucleic acid amplification testing (NAAT) and immunoglobulin M (IgM) testing within days after birth. Brain and eye defects highly specific for congenital ZIKV infection have been described; sporadic reports have documented negative ZIKV testing in such infants. METHODS: Infants from the U.S. Zika Pregnancy and Infant Registry and Zika Birth Defects Surveillance with Zika-associated birth defects and maternal and infant laboratory testing for ZIKV and two congenital infections (i.e., cytomegalovirus [CMV] and toxoplasmosis) were reviewed for phenotype and laboratory results. Infants with at least one defect considered highly specific for congenital ZIKV infection were designated as having congenital Zika syndrome (CZS) clinical phenotype for this study. RESULTS: Of 325 liveborn infants with Zika-associated birth defects and laboratory evidence of maternal ZIKV infection, 33 (10%) had CZS clinical phenotype; 171 (53%) had ZIKV IgM testing with negative or no ZIKV NAAT. ZIKV IgM was negative in the remaining 120 infants, and for 90%, testing for CMV and toxoplasmosis was missing/incomplete. Among 11 infants testing negative for ZIKV IgM, CMV, and toxoplasmosis, 2 infants had CZS clinical phenotype. CONCLUSIONS: These data add support to previous reports of negative ZIKV IgM testing in infants with clear maternal and phenotypic evidence of congenital ZIKV infection. Follow-up care consistent with the diagnosis is recommended regardless of infant ZIKV test results. |
Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settings.
Dolk H , Leke AZ , Whitfield P , Moore R , Karnell K , Barišić I , Barlow-Mosha L , Botto LD , Garne E , Guatibonza P , Godfred-Cato S , Halleux CM , Holmes LB , Moore CA , Orioli I , Raina N , Valencia D . Birth Defects Res 2021 113 (14) 1057-1073 BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The "basic" version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The "surveillance" version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The "basic" version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance" version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care. |
Modification of the association between diabetes and birth defects by obesity, National Birth Defects Prevention Study, 1997-2011
Tinker SC , Gilboa SM , Moore CA , Waller DK , Simeone RM , Kim SY , Jamieson DJ , Botto LD , Fisher SC , Reefhuis J . Birth Defects Res 2021 113 (14) 1084-1097 BACKGROUND: Maternal pregestational diabetes and obesity are risk factors for birth defects. Diabetes and obesity often occur together; it is unclear whether their co-occurrence compounds birth defect risk. METHODS: We analyzed 1997-2011 data on 29,671 cases and 10,963 controls from the National Birth Defects Prevention Study, a multisite case-control study. Mothers self-reported height, pregestational weight, and diabetes (pregestational and gestational; analyzed separately). We created four exposure groups: no obesity or diabetes (referent), obesity only, diabetes only, and both obesity and diabetes. We estimated odds ratios (ORs) using logistic regression and the relative excess risk due to interaction (RERI). RESULTS: Among mothers with pregestational obesity without diabetes, modest associations (OR range: 1.1-1.5) were observed for neural tube defects, small intestinal atresia, anorectal atresia, renal agenesis/hypoplasia, omphalocele, and several congenital heart defects. Pregestational diabetes, regardless of obesity, was strongly associated with most birth defects (OR range: 2.0-75.9). Gestational diabetes and obesity had a stronger association than for obesity alone and the RERI (in parentheses) suggested additive interaction for hydrocephaly (1.2; 95% confidence interval [CI]: -0.1, 2.5), tetralogy of Fallot (0.9; 95% CI: -0.01, 1.8), atrioventricular septal defect (1.1; 95% CI: -0.1, 2.3), hypoplastic left heart syndrome (1.1; 95% CI: -0.2, 2.4), and atrial septal defect secundum or not otherwise specified (1.0; 95% CI: 0.3, 1.6; only statistically significant RERI). CONCLUSIONS: Our results do not support a synergistic relationship between obesity and diabetes for most birth defects examined. However, there are opportunities for prevention by reducing obesity and improving glycemic control among women with pregestational diabetes before conception. |
Microcephaly Outcomes among Zika Virus-Infected Pregnant Women in Honduras
Alger J , Buekens P , Cafferata ML , Alvarez Z , Berrueta M , Bock H , Bustillo C , Calderón A , Callejas A , Castillo M , Ciganda A , Fúnes J , García J , García K , Gibbons L , Gilboa SM , Harville EW , Hernández G , López R , López W , Lorenzana I , Tulio Luque M , Maldonado C , Moore CA , Ochoa C , Parham L , Pastrana K , Rico F , Rodríguez H , Stella C , Valencia D , Varela D , Wesson DM , Zúniga C , Tong VT . Am J Trop Med Hyg 2021 104 (5) 1737-1740 The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase-PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3-77.7%) risk of HC more than three SDs below the mean. |
Zika virus-associated birth defects, Costa Rica, 2016-2018
Benavides-Lara A , la Paz Barboza-Arguello M , González-Elizondo M , Hernández-deMezerville M , Brenes-Chacón H , Ramírez-Rojas M , Ramírez-Hernández C , Arjona-Ortegón N , Godfred-Cato S , Valencia D , Moore CA , Soriano-Fallas A . Emerg Infect Dis 2021 27 (2) 360-71 After Zika virus (ZIKV) infection in Costa Rica was confirmed in January 2016, the national surveillance system was enhanced to monitor associated birth defects. To characterize the ZIKV outbreak among live-born infants during March 2016-March 2018, we conducted a descriptive analysis. Prevalence of ZIKV-associated birth defects was 15.3 cases/100,000 live births. Among 22 infants with ZIKV-associated birth defects, 11 were designated as confirmed (positive for ZIKV) and 11 were designated as probable cases (negative for ZIKV or not tested, but mother was expsed to ZIKV during pregnancy). A total of 91% had microcephaly (head circumference >2 SDs below mean for age and sex), 64% severe microcephaly (head circumference >3 SDs below mean for age and sex), 95% neurodevelopmental abnormalities, 82% brain anomalies, 41% eye abnormalities, and 9% hearing loss. Monitoring children for >1 year can increase identification of ZIKV-associated abnormalities in addition to microcephaly. | Enhanced birth defect surveillance increased identification of virus-associated abnormalities, including microcephaly. | eng |
Measurement of head circumference: Implications for microcephaly surveillance in Zika-affected areas
Harville EW , Tong VT , Gilboa SM , Moore CA , Cafferata ML , Alger J , Gibbons L , Bustillo C , Callejas A , Castillo M , Fúnes J , García J , Hernández G , López W , Ochoa C , Rico F , Rodríguez H , Zúniga C , Ciganda A , Stella C , Tomasso G , Buekens P . Trop Med Infect Dis 2020 6 (1) Worldwide recognition of the Zika virus outbreak in the Americas was triggered by an unexplained increase in the frequency of microcephaly. While severe microcephaly is readily identifiable at birth, diagnosing less severe cases requires comparison of head circumference (HC) measurement to a growth chart. We examine measured values of HC and digit preference in those values, and, by extension, the prevalence of microcephaly at birth in two data sources: a research study in Honduras and routine surveillance data in Uruguay. The Zika in Pregnancy in Honduras study enrolled pregnant women prenatally and followed them until delivery. Head circumference was measured with insertion tapes (SECA 212), and instructions including consistent placement of the tape and a request to record HC to the millimeter were posted where newborns were examined. Three indicators of microcephaly were calculated: (1) HC more than 2 standard deviations (SD) below the mean, (2) HC more than 3 SD below the mean (referred to as "severe microcephaly") and (3) HC less than the 3rd percentile for sex and gestational age, using the INTERGROWTH-21st growth standards. We compared these results from those from a previous analysis of surveillance HC data from the Uruguay Perinatal Information System (Sistema Informático Perinatal (SIP). Valid data on HC were available on 579 infants, 578 with gestational age data. Nine babies (1.56%, 95% CI 0.71-2.93) had HC < 2SD, including two (0.35%, 95% CI 0.04-1.24) with HC < 3SD, and 11 (1.9%, 95% CI, 0.79-3.02) were below the 3rd percentile. The distribution of HC showed strong digit preference: 72% of measures were to the whole centimeter (cm) and 19% to the half-cm. Training and use of insertion tapes had little effect on digit preference, nor were overall HC curves sufficient to detect an increase in microcephaly during the Zika epidemic in Honduras. When microcephaly prevalence needs to be carefully analyzed, such as during the Zika epidemic, researchers may need to interpret HC data with caution. |
Discordant Clinical Outcomes in a Monozygotic Dichorionic-Diamniotic Twin Pregnancy with Probable Zika Virus Exposure. Case Report.
Mercado M , Daza M , Moore CA , Valencia D , Rico A , Álvarez-Diaz DA , Brault AC , Fitzpatrick K , Mulkey SB . Trop Med Infect Dis 2020 5 (4) Prenatal exposure to Zika virus (ZIKV) is associated with congenital anomalies of the brain and the eye and neurodevelopmental sequelae. The spectrum of disease outcomes may relate to timing of infection as well as genetic and environmental factors. Congenital infections occurring in twin pregnancies can inform the clinical spectrum of these conditions and provide unique information regarding timing of infection and in utero environment with disease pathophysiology. Herein, we report a monozygotic dichorionic-diamniotic twin pregnancy with probable prenatal ZIKV exposure identified through the Colombian ZIKV disease surveillance system. Multidisciplinary clinical evaluations were provided to the twins during their first three years of life through a national program for children with in utero ZIKV exposure. Laboratory evidence of congenital infection as well as microcephaly, brain, eye, and neurodevelopmental compromise related to prenatal ZIKV infection were identified in only one infant of the twin pregnancy. This is the first report of monozygotic twins discordant for Zika-associated birth defects. The evaluation of the pathophysiology of discordance in disease outcome for congenital infections in twin pregnancies may lead to a better understanding of potential complex environmental and genetic interactions between the mother, her offspring, and an infectious exposure. |
2018 Zika Health Brigade: Delivering critical health screening in the U.S. Virgin Islands
Godfred-Cato S , Fehrenbach SN , Reynolds MR , Galang RR , Schoelles D , Brown-Shuler L , Hillman B , DeWilde L , Prosper A , Hudson A , Moore CA , Ellis EM . Trop Med Infect Dis 2020 5 (4) In 2017, Hurricanes Irma and Maria caused significant damage to the United States Virgin Islands (USVI), heightening the challenges many residents faced in accessing adequate healthcare and receiving recommended Zika virus screening services. To address this challenge, the USVI Department of Health (DOH) requested technical assistance from the Centers for Disease Control and Prevention (CDC), the Health Resources and Services Administration (HRSA), and the American Academy of Pediatrics (AAP) to organize a health brigade to bring needed medical care to an underserved population. It also established the development of important partnerships between federal and private partners as well as between clinical providers and public health entities such as the Epidemiology & Disease Reporting, Maternal Child Health (MCH), and Infant and Toddlers Programs within the DOH, and local clinicians. This health brigade model could be replicated to ensure recommended evaluations are delivered to populations that may have unmet medical needs due to the complexity of the conditions and/or rural location. |
Early growth parameters as predictors of developmental delay among children conceived during the 2015-2016 Zika virus outbreak in northeastern Brazil
Rose CE , Bertolli J , Attell JE , Moore CA , Melo F , Kotzky K , Krishna N , Satterfield-Nash A , Pereira IO , Pessoa A , Smith DC , Santelli Acfes , Peacock G . Trop Med Infect Dis 2020 5 (4) BACKGROUND: Identifying infants with congenital infection for early intervention will likely be challenging in future Zika virus outbreaks. We investigated indicators of risk for developmental delay among children born with and without obvious manifestations of congenital Zika virus infection. METHODS: We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraíba, Brazil. We analyzed data from children at birth; ages 1-7 months and approximately 24 months, using medical records (i.e., anthropometric measurements diagnoses), medical evaluation (i.e., Zika/other laboratory tests, dysmorphic features), and parent report (seizures, developmental delay). We used a Bayesian modeling approach to identify predictors of developmental delay. RESULTS: Head circumference (HC) and length at birth and rates of growth for HC and length at follow-up were consistent across domains of developmental delay; (e.g., for every 1 cm per month decrease in HC growth rate; there was a corresponding decrease in the gross motor z-score). Modeling results indicated that HC and length at birth, and follow-up HC and length rates of growth, were predictive of developmental delay. CONCLUSION: These findings suggest that accurate measurement and frequent monitoring of HC and length, especially in the first few months of life, may be useful for identifying children possibly congenitally exposed to Zika virus who could benefit from early intervention services. |
Neurodevelopmental findings in children 20-30 months of age with postnatal Zika infection at 1-12 months of age, Colombia, September-November 2017
Pacheco O , Newton SM , Daza M , Cates JE , Reales JAM , Burkel VK , Mercado M , Godfred-Cato S , Gonzalez M , Anderson KN , Woodworth KR , Valencia D , Tong VT , Gilboa SM , Osorio MB , Rodriguez DYS , Prieto-Alvarado FE , Moore CA , Honein MA , Ospina Martinez ML . Paediatr Perinat Epidemiol 2020 35 (1) 92-97 BACKGROUND: Zika virus (ZIKV) infection during pregnancy can cause infant brain and eye abnormalities and has been associated with adverse neurodevelopmental outcomes in exposed infants. Evidence is limited on ZIKV's effects on children infected postnatally within the first year of life. OBJECTIVE: To determine whether any adverse neurodevelopmental outcomes occurred in early childhood for children infected postnatally with ZIKV during infancy, given the neurotoxicity of ZIKV infection and the rapid brain development that occurs in infancy and early childhood. METHODS: The Colombia Instituto Nacional de Salud (INS) conducted health and developmental screenings between September and November 2017 to evaluate 60 children at ages 20-30 months who had laboratory-confirmed symptomatic postnatal ZIKV infection at ages 1-12 months. We examined the frequency of adverse neurologic, hearing, eye, and developmental outcomes as well as the relationship between age at Zika symptom onset and developmental outcomes. RESULTS: Nine of the 60 (15.0%) children had adverse outcomes on the neurologic, hearing, or eye examination. Six of the 47 (12.8%) children without these adverse findings, and who received a valid developmental screening, had an alert score in the hearing-language domain which signals the need for additional developmental evaluation. CONCLUSION: Neurologic, hearing, eye, and developmental findings suggest reassuring results. Since the full spectrum of neurodevelopmental outcomes in children postnatally infected with ZIKV remains unknown, routine paediatric care is advised to monitor the development of these children to ensure early identification of any adverse neurodevelopmental outcomes. |
Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia.
Galang RR , Avila GA , Valencia D , Daza M , Tong VT , Bermudez AJ , Gilboa SM , Rico A , Cates J , Pacheco O , Winfield CM , Prieto F , Honein MA , Cortes LJ , Moore CA , Ospina ML . J Pediatr 2020 222 112-119 e3 OBJECTIVE: To estimate the prevalence of microcephaly and central nervous system (CNS) defects during the Zika virus (ZIKV) epidemic in Colombia and proportion attributable to congenital ZIKV infection. STUDY DESIGN: Clinical and laboratory data for cases of microcephaly and/or CNS defects reported to national surveillance between 2015 and 2017 were reviewed and classified by a panel of clinical subject matter experts. Maternal and fetal/infant biologic specimens were tested for congenital infection and chromosomal abnormalities. Infants/fetuses with microcephaly and/or CNS defects (cases) were classified into broad etiologic categories (teratogenic, genetic, multifactorial, and unknown). Cases classified as potentially attributable to congenital ZIKV infection were stratified by strength of evidence for ZIKV etiology (strong, moderate, or limited) using a novel strategy considering birth defects unique or specific to ZIKV or other infections and laboratory evidence. RESULTS: Among 858 reported cases with sufficient information supporting a diagnosis of microcephaly or CNS defects, 503 were classified as potentially attributable to congenital ZIKV infection. Of these, the strength of evidence was considered strong in 124 (24.7%) cases; moderate in 232 (46.1%) cases; and limited in 147 (29.2%). Of the remaining, 355 (41.4%) were attributed to etiologies other than ZIKV infection (syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes 1 and herpes 2 viruses only, n = 32 [3.7%]; genetic, n = 16 [1.9%]; multifactorial, n = 42 [4.9%]; unknown, n = 265 [30.9%]). CONCLUSIONS: Fifty-eight percent of cases of microcephaly and/or CNS defects were potentially attributable to congenital ZIKV infection; however, the strength of evidence varied considerably. This surveillance protocol might serve as a model approach for investigation and etiologic classification of complex congenital conditions. |
Functional outcomes among a cohort of children in northeastern Brazil meeting criteria for follow-up of congenital Zika virus infection
Bertolli J , Attell JE , Rose C , Moore CA , Melo F , Staples JE , Kotzky K , Krishna N , Satterfield-Nash A , Pereira IO , Pessoa A , Smith DC , Faria e Silva Santelli AC , Boyle CA , Peacock G . Am J Trop Med Hyg 2020 102 (5) 955-963 Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraiba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention. |
Population-based surveillance for birth defects potentially related to Zika virus infection - 22 states and territories, January 2016-June 2017
Smoots AN , Olson SM , Cragan J , Delaney A , Roth NM , Godfred-Cato S , Jones AM , Nahabedian JF 3rd , Fornoff J , Sandidge T , Yazdy MM , Higgins C , Olney RS , Eckert V , Forkner A , Fox DJ , Stolz A , Crawford K , Cho SJ , Knapp M , Ahmed MF , Lake-Burger H , Elmore AL , Langlois P , Breidenbach R , Nance A , Denson L , Caton L , Forestieri N , Bergman K , Humphries BK , Leedom VO , Tran T , Johnston J , Valencia-Prado M , Perez-Gonzalez S , Romitti PA , Fall C , Bryan JM , Barton J , Arias W , St John K , Mann S , Kimura J , Orantes L , Martin B , de Wilde L , Ellis EM , Song Z , Akosa A , Goodroe C , Ellington SR , Tong VT , Gilboa SM , Moore CA , Honein MA . MMWR Morb Mortal Wkly Rep 2020 69 (3) 67-71 Zika virus infection during pregnancy can cause congenital brain and eye abnormalities and is associated with neurodevelopmental abnormalities (1-3). In areas of the United States that experienced local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased in the second half of 2016 compared with the first half (4). To update the previous report, CDC analyzed population-based surveillance data from 22 states and territories to estimate the prevalence of birth defects potentially related to Zika virus infection, regardless of laboratory evidence of or exposure to Zika virus, among pregnancies completed during January 1, 2016-June 30, 2017. Jurisdictions were categorized as those 1) with widespread local transmission of Zika virus; 2) with limited local transmission of Zika virus; and 3) without local transmission of Zika virus. Among 2,004,630 live births, 3,359 infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy were identified (1.7 per 1,000 live births, 95% confidence interval [CI] = 1.6-1.7). In areas with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy was significantly higher during the quarters comprising July 2016-March 2017 (July-September 2016 = 3.0; October-December 2016 = 4.0; and January-March 2017 = 5.6 per 1,000 live births) compared with the reference period (January-March 2016) (1.3 per 1,000). These findings suggest a fourfold increase (prevalence ratio [PR] = 4.1, 95% CI = 2.1-8.4) in birth defects potentially related to Zika virus in widespread local transmission areas during January-March 2017 compared with that during January-March 2016, with the highest prevalence (7.0 per 1,000 live births) in February 2017. Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance. |
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