Hospitalizations and Deaths Associated with EVALI.

BACKGROUND: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). METHODS: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. RESULTS: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. CONCLUSIONS: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

Myocarditis in Minnehaha County, South Dakota, 1880-1939.

From 1920 to 1940 in Minnehaha County there was an apparent striking increase in the incidence of fatal myocarditis and chronic myocarditis. Based on an analysis of the interment records of the Mt. Pleasant Cemetery, word frequency studies in two prominent American medical journals and a general review of related medical publications, we explore this increase. We conclude that there was no actual increase in the frequency of inflammatory disorders of the myocardium in Minnehaha County during this period. Rather, it appears that the use of the diagnostic terms was a matter of choice among local physicians that was not supported by contemporaneous clinical and pathophysiologic publications in available journals.

Fatal Accidental Drowning in Minnehaha County, South Dakota, 1880-1939.

Drowning is currently the second leading cause of injury-related death for children 1-4 years of age in the United States and is the leading cause of death worldwide for boys ages 5-14 years. The World Health Organization (WHO) classifies it as a public health threat and advocates for reducing drowning deaths by understanding geographical, cultural, and societal risk factors. To these three we added a fourth: historical studies. To that end, we analyzed accidental causes of death between January 1, 1880, and December 31, 1939, in Minnehaha County, South Dakota, based on interment records from the Mt. Pleasant Cemetery. From these six decades (1880-1939) of data, we classified 217 cases as accidental deaths. Drowning was the leading cause of accidental mortality, accounting for 50 accidental deaths (23%). Drowning deaths were analyzed by the decedents' age and date of death. We discuss specific historical drowning risk factors and hypothesize how they may have affected drowning deaths from 1880-1939 in Minnehaha County.

Urban-rural differences in pregnancy-related deaths, United States, 2011-2016.

BACKGROUND: The US pregnancy-related mortality ratio has not improved over the past decade and includes striking disparities by race and ethnicity and by state. Understanding differences in pregnancy-related mortality across and within urban and rural areas can guide the development of interventions for preventing future pregnancy-related deaths. OBJECTIVE: We sought to compare pregnancy-related mortality across and within urban and rural counties by race and ethnicity and age. STUDY DESIGN: We conducted a descriptive analysis of 3747 pregnancy-related deaths during 2011-2016 (the most recent available data) with available zone improvement plan code or county data in the Pregnancy Mortality Surveillance System, among Hispanic and non-Hispanic White, Black, American Indian or Alaska Native, and Asian or Pacific Islander women aged 15 to 44 years. We aggregated data by US county and grouped counties per the National Center for Health Statistics Urban-Rural Classification Scheme for Counties. We used R statistical software, epitools, to calculate the pregnancy-related mortality ratio (number of pregnancy-related deaths per 100,000 live births) for each urban-rural grouping, obtain 95% confidence intervals, and perform exact tests of ratio comparisons using the Poisson distribution. RESULTS: Of the total 3747 pregnancy-related deaths analyzed, 52% occurred in large metro counties, and 7% occurred in noncore (rural) counties. Large metro counties had the lowest pregnancy-related mortality ratio (14.8; 95% confidence interval, 14.2-15.5), whereas noncore counties had the highest (24.1; 95% confidence interval, 21.4-27.1), including race and ethnicity and age groups. Pregnancy-related mortality ratio age disparities increased with rurality. Women aged 25 to 34 years and 35 to 44 years living in noncore counties had pregnancy-related mortality ratios 1.5 and 3 times higher, respectively, than women of the same age groups in large metro counties. Within each urban-rural category, pregnancy-related mortality ratios were higher among non-Hispanic Black women than non-Hispanic White women. Non-Hispanic American Indian or Alaska Native pregnancy-related mortality ratios in small metro, micropolitan, and noncore counties were 2 to 3 times that of non-Hispanic White women in the same areas. CONCLUSION: Although more than half of pregnancy-related deaths occurred in large metro counties, the pregnancy-related mortality ratio rose with increasing rurality. Disparities existed in urban-rural categories, including by age group and race and ethnicity. Geographic location is an important context for initiatives to prevent future deaths and eliminate disparities. Further research is needed to better understand reasons for the observed urban-rural differences and to guide a multifactorial response to reduce pregnancy-related deaths.

Pregnant? Validity of the pregnancy checkbox on death certificates in four states, and characteristics associated with pregnancy checkbox errors.

BACKGROUND: Maternal mortality rates in the United States appear to be increasing. One potential reason may be increased identification of maternal deaths after the addition of a pregnancy checkbox to the death certificate. In 2016, 4 state health departments (Georgia, Louisiana, Michigan, and Ohio) implemented a pregnancy checkbox quality assurance pilot, with technical assistance provided by the Centers for Disease Control and Prevention. The pilot aimed to improve accuracy of the pregnancy checkbox on death certificates and resultant state maternal mortality estimates. OBJECTIVE: To estimate the validity of the pregnancy checkbox on the death certificate, and to describe characteristics associated with errors using 2016 data from a 4-state quality assurance pilot. MATERIALS AND METHODS: Potential pregnancy-associated deaths were identified by linking death certificates with birth or fetal death certificates from within 1 year preceding death or by pregnancy checkbox status. Death certificates that indicated that the decedent was pregnant within 1 year of death via the pregnancy checkbox, but that did not link to a birth or fetal death certificate, were referred for active follow-up to confirm pregnancy status by either death certifier confirmation or medical record review. Descriptive statistics and 95% confidence intervals were used to examine the distributions of demographic characteristics by pregnancy confirmation category (confirmed pregnant, confirmed not pregnant, and unable to confirm). We compared the proportion confirmed pregnant and confirmed not pregnant within age, race/ethnicity, pregnancy checkbox category, and certifier type categories using a Wald test of proportions. Binomial and Poisson regression models were used to estimate prevalence ratios for having an incorrect pregnancy checkbox (false positive, false negative) by age group, race/ethnicity, pregnancy checkbox category, and certifier type. RESULTS: Among 467 potential pregnancy-associated deaths, 335 (72%) were confirmed pregnant via linkage to a birth or fetal death certificate, certifier confirmation, or review of medical records. A total of 97 women (21%) were confirmed not pregnant (false positives) and 35 (7%) were unable to be confirmed. Women confirmed pregnant were significantly younger than women confirmed not pregnant (P < .001). Deaths certified by coroners and medical examiners were more likely to be confirmed pregnant than confirmed not pregnant (P = .04). The association between decedent age category and false-positive status followed a dose-response relationship (P < .001), with increasing prevalence ratios for each increase in age category. Death certificates of non-Hispanic black women were more likely to be false positive, compared with non-Hispanic white women (prevalence ratio, 1.41; 95% confidence interval, 1.01, 1.96). The sensitivity of the pregnancy checkbox among these 4 states in 2016 was 62% and the positive predictive value was 68%. CONCLUSION: We provide a multi-state analysis of the validity of the pregnancy checkbox and highlight a need for more accurate reporting of pregnancy status on death certificates. States and other jurisdictions may increase the accuracy of their data used to calculate maternal mortality rates by implementing quality assurance processes.

Using Supervised Learning Methods to Develop a List of Prescription Medications of Greatest Concern during Pregnancy.

INTRODUCTION: Women and healthcare providers lack adequate information on medication safety during pregnancy. While resources describing fetal risk are available, information is provided in multiple locations, often with subjective assessments of available data. We developed a list of medications of greatest concern during pregnancy to help healthcare providers counsel reproductive-aged and pregnant women. METHODS: Prescription drug labels submitted to the U.S. Food and Drug Administration with information in the Teratogen Information System (TERIS) and/or Drugs in Pregnancy and Lactation by Briggs & Freeman were included (N = 1,186 medications; 766 from three data sources, 420 from two). We used two supervised learning methods ('support vector machine' and 'sentiment analysis') to create prediction models based on narrative descriptions of fetal risk. Two models were created per data source. Our final list included medications categorized as 'high' risk in at least four of six models (if three data sources) or three of four models (if two data sources). RESULTS: We classified 80 prescription medications as being of greatest concern during pregnancy; over half were antineoplastic agents (n = 24), angiotensin converting enzyme inhibitors (n = 10), angiotensin II receptor antagonists (n = 8), and anticonvulsants (n = 7). DISCUSSION: This evidence-based list could be a useful tool for healthcare providers counseling reproductive-aged and pregnant women about medication use during pregnancy. However, providers and patients may find it helpful to weigh the risks and benefits of any pharmacologic treatment for both pregnant women and the fetus when managing medical conditions before and during pregnancy.

Assessing the Burden of Neonatal Abstinence Syndrome: Validation of ICD-9-CM Data, Florida, 2010-2011.

CONTEXT: On October 1, 2015, the United States transitioned from using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to ICD-10-CM. Continuing to monitor the burden of neonatal abstinence syndrome (NAS) after the transition presently requires use of data dependent on ICD-9-CM coding to enable trend analyses. Little has been published on the validation of using ICD-9-CM codes to identify NAS cases. OBJECTIVE: To assess the validity of hospital discharge data (HDD) from selected Florida hospitals for passive NAS surveillance, based on ICD-9-CM codes, which are used to quantify baseline prevalence of NAS. DESIGN: We reviewed infant and maternal data for all births at 3 Florida hospitals from 2010 to 2011. Potential NAS cases included infants with ICD-9-CM discharge codes 779.5 and/or 760.72 in linked administrative data (ie, HDD linked to vital records) or in unlinked HDD and infants identified through review of neonatal intensive care unit admission logs or inpatient pharmacy records. Confirmed infant cases met 3 clinician-proposed criteria. Sensitivity and positive predictive value were calculated to assess validity for the 2 ICD-9-CM codes, individually and combined. RESULTS: Of 157 confirmed cases, 134 with 779.5 and/or 760.72 codes were captured in linked HDD (sensitivity = 85.4%) and 151 in unlinked HDD (sensitivity = 96.2%). Positive predictive value was 74.9% for linked HDD and 75.5% for unlinked HDD. For either HDD types, the single 779.5 code had the highest positive predictive value (86%), lowest number of false positives, and good to excellent sensitivity. CONCLUSIONS: Passive surveillance using ICD-9-CM code 779.5 in either linked or unlinked HDD identified NAS cases with reasonable validity. Our work supports the use of ICD-9-CM code 779.5 to assess the baseline prevalence of NAS through 2015.

Vital Signs: Pregnancy-Related Deaths, United States, 2011-2015, and Strategies for Prevention, 13 States, 2013-2017.

BACKGROUND: Approximately 700 women die from pregnancy-related complications in the United States every year. METHODS: Data from CDC's national Pregnancy Mortality Surveillance System (PMSS) for 2011-2015 were analyzed. Pregnancy-related mortality ratios (pregnancy-related deaths per 100,000 live births; PRMRs) were calculated overall and by sociodemographic characteristics. The distribution of pregnancy-related deaths by timing relative to the end of pregnancy and leading causes of death were calculated. Detailed data on pregnancy-related deaths during 2013-2017 from 13 state maternal mortality review committees (MMRCs) were analyzed for preventability, factors that contributed to pregnancy-related deaths, and MMRC-identified prevention strategies to address contributing factors. RESULTS: For 2011-2015, the national PRMR was 17.2 per 100,000 live births. Non-Hispanic black (black) women and American Indian/Alaska Native women had the highest PRMRs (42.8 and 32.5, respectively), 3.3 and 2.5 times as high, respectively, as the PRMR for non-Hispanic white (white) women (13.0). Timing of death was known for 87.7% (2,990) of pregnancy-related deaths. Among these deaths, 31.3% occurred during pregnancy, 16.9% on the day of delivery, 18.6% 1-6 days postpartum, 21.4% 7-42 days postpartum, and 11.7% 43-365 days postpartum. Leading causes of death included cardiovascular conditions, infection, and hemorrhage, and varied by timing. Approximately sixty percent of pregnancy-related deaths from state MMRCs were determined to be preventable and did not differ significantly by race/ethnicity or timing of death. MMRC data indicated that multiple factors contributed to pregnancy-related deaths. Contributing factors and prevention strategies can be categorized at the community, health facility, patient, provider, and system levels and include improving access to, and coordination and delivery of, quality care. CONCLUSIONS: Pregnancy-related deaths occurred during pregnancy, around the time of delivery, and up to 1 year postpartum; leading causes varied by timing of death. Approximately three in five pregnancy-related deaths were preventable. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Strategies to address contributing factors to pregnancy-related deaths can be enacted at the community, health facility, patient, provider, and system levels.

Racial/Ethnic Disparities in Pregnancy-Related Deaths - United States, 2007-2016.

Approximately 700 women die in the United States each year as a result of pregnancy or its complications, and significant racial/ethnic disparities in pregnancy-related mortality exist (1). Data from CDC's Pregnancy Mortality Surveillance System (PMSS) for 2007-2016 were analyzed. Pregnancy-related mortality ratios (PRMRs) (i.e., pregnancy-related deaths per 100,000 live births) were analyzed by demographic characteristics and state PRMR tertiles (i.e., states with lowest, middle, and highest PRMR); cause-specific proportionate mortality by race/ethnicity also was calculated. Over the period analyzed, the U.S. overall PRMR was 16.7 pregnancy-related deaths per 100,000 births. Non-Hispanic black (black) and non-Hispanic American Indian/Alaska Native (AI/AN) women experienced higher PRMRs (40.8 and 29.7, respectively) than did all other racial/ethnic groups. This disparity persisted over time and across age groups. The PRMR for black and AI/AN women aged ≥30 years was approximately four to five times that for their white counterparts. PRMRs for black and AI/AN women with at least some college education were higher than those for all other racial/ethnic groups with less than a high school diploma. Among state PRMR tertiles, the PRMRs for black and AI/AN women were 2.8-3.3 and 1.7-3.3 times as high, respectively, as those for non-Hispanic white (white) women. Significant differences in cause-specific proportionate mortality were observed among racial/ethnic populations. Strategies to address racial/ethnic disparities in pregnancy-related deaths, including improving women's health and access to quality care in the preconception, pregnancy, and postpartum periods, can be implemented through coordination at the community, health facility, patient, provider, and system levels.

Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E-cigarette, or Vaping, Product Use Associated Lung Injury - United States, October 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical partners are investigating a multistate outbreak of lung injury associated with the use of electronic cigarette (e-cigarette), or vaping, products. In late August, CDC released recommendations for health care providers regarding e-cigarette, or vaping, product use associated lung injury (EVALI) based on limited data from the first reported cases (1,2). This report summarizes national surveillance data describing clinical features of more recently reported cases and interim recommendations based on these data for U.S. health care providers caring for patients with suspected or known EVALI. It provides interim guidance for 1) initial clinical evaluation; 2) suggested criteria for hospital admission and treatment; 3) patient follow-up; 4) special considerations for groups at high risk; and 5) clinical and public health recommendations. Health care providers evaluating patients suspected to have EVALI should ask about the use of e-cigarette, or vaping, products in a nonjudgmental and thorough manner. Patients suspected to have EVALI should have a chest radiograph (CXR), and hospital admission is recommended for patients who have decreased blood oxygen (O2) saturation (<95%) on room air or who are in respiratory distress. Health care providers should consider empiric use of a combination of antibiotics, antivirals, or steroids based upon clinical context. Evidence-based tobacco product cessation strategies, including behavioral counseling, are recommended to help patients discontinue use of e-cigarette, or vaping, products. To reduce the risk of recurrence, patients who have been treated for EVALI should not use e-cigarette, or vaping, products. CDC recommends that persons should not use e-cigarette, or vaping, products that contain tetrahydrocannabinol (THC). At present, CDC recommends persons consider refraining from using e-cigarette, or vaping, products that contain nicotine. Irrespective of the ongoing investigation, e-cigarette, or vaping, products should never be used by youths, young adults, or women who are pregnant. Persons who do not currently use tobacco products should not start using e-cigarette, or vaping, products.

Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019.

CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products.

Clinical Course of a Patient With Kidney Failure Due to Isolated Bilateral Renal Extramedullary Plasmacytomas.

Plasmacytomas are rare immunoproliferative monoclonal plasma cell diseases of lymphoid lineage that may present in an isolated or systemic manner. Systemic involvement is much more common than occurrences isolated to a particular organ, and for this reason, it is imperative to rule out systemic involvement for osseous and nonosseous isolated neoplasms. These neoplasms present unique challenges due to their location, extent of involvement, vague presentation, and dearth of treatment protocol. We report the case of a 69-year-old man who developed chronic kidney disease stage 4 between 2009 and 2012. Precipitous kidney failure, anorexia, fatigue, and flank pain necessitated clinical follow-up that ultimately led to thorough imaging and bilateral kidney biopsy. Protein electrophoresis, immunohistochemistry, and immunofluorescence were all consistent with bilateral renal extramedullary plasmacytomas. Treatment recommendations are often limited to prior case successes; however, chemotherapy, radiation, and surgery are the mainstay of treatment. Although surgery or combined therapy provides the best results for patients, such options are unfeasible with bilateral kidney involvement. Therefore, a chemotherapy regimen, similar to that for multiple myeloma, was determined to be most reasonable. Treatment consisted of 4 cycles of a bortezomib, cyclophosphamide, and dexamethasone regimen. Three months following chemotherapy, kidney function returned to baseline levels.

Association Between Infant Mortality Attributable to Birth Defects and Payment Source for Delivery - United States, 2011-2013.

Birth defects are a leading cause of infant mortality in the United States (1), accounting for approximately 20% of infant deaths. The rate of infant mortality attributable to birth defects (IMBD) in the United States in 2014 was 11.9 per 10,000 live births (1). Rates of IMBD differ by race/ethnicity (2), age group at death (2), and gestational age at birth (3). Insurance type is associated with survival among infants with congenital heart defects (CHD) (4). In 2003, a checkbox indicating principal payment source for delivery was added to the U.S. standard birth certificate (5). To assess IMBD by payment source for delivery, CDC analyzed linked U.S. birth/infant death data for 2011-2013 from states that adopted the 2003 revision of the birth certificate. The results indicated that IMBD rates for preterm (<37 weeks of gestation) and term (≥37 weeks) infants whose deliveries were covered by Medicaid were higher during the neonatal (<28 days) and postneonatal (≥28 days to <1 year) periods compared with infants whose deliveries were covered by private insurance. Similar differences in postneonatal mortality were observed for the three most common categories of birth defects listed as a cause of death: central nervous system (CNS) defects, CHD, and chromosomal abnormalities. Strategies to ensure quality of care and access to care might reduce the difference between deliveries covered by Medicaid and those covered by private insurance.

Baseline Prevalence of Birth Defects Associated with Congenital Zika Virus Infection - Massachusetts, North Carolina, and Atlanta, Georgia, 2013-2014.

Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown (1). To better understand the impact of birth defects resulting from Zika virus infection, the CDC surveillance case definition established in 2016 for birth defects potentially related to Zika virus infection* (2) was retrospectively applied to population-based birth defects surveillance data collected during 2013-2014 in three areas before the introduction of Zika virus (the pre-Zika years) into the World Health Organization's Region of the Americas (Americas) (3). These data, from Massachusetts (2013), North Carolina (2013), and Atlanta, Georgia (2013-2014), included 747 infants and fetuses with one or more of the birth defects meeting the case definition (pre-Zika prevalence = 2.86 per 1,000 live births). Brain abnormalities or microcephaly were the most frequently recorded (1.50 per 1,000), followed by neural tube defects and other early brain malformations† (0.88), eye abnormalities without mention of a brain abnormality (0.31), and other consequences of central nervous system (CNS) dysfunction without mention of brain or eye abnormalities (0.17). During January 15-September 22, 2016, the U.S. Zika Pregnancy Registry (USZPR) reported 26 infants and fetuses with these same defects among 442 completed pregnancies (58.8 per 1,000) born to mothers with laboratory evidence of possible Zika virus infection during pregnancy (2). Although the ascertainment methods differed, this finding was approximately 20 times higher than the proportion of one or more of the same birth defects among pregnancies during the pre-Zika years. These data demonstrate the importance of population-based surveillance for interpreting data about birth defects potentially related to Zika virus infection.

Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure - United States (Including U.S. Territories), July 2017.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

Evaluation of Placental and Fetal Tissue Specimens for Zika Virus Infection - 50 States and District of Columbia, January-December, 2016.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection.

Vital Signs: Update on Zika Virus-Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure - U.S. Zika Pregnancy Registry, 2016.

BACKGROUND: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. METHODS: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. RESULTS: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

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).

Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy.

Importance: Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births. Objective: To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. Design, Setting, and Participants: Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. Exposures: Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. Main Outcomes and Measures: Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. Results: Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. Conclusions and Relevance: Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.