Zika Virus Disease and Pregnancy Outcomes in Colombia.

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

Prenatal ultrasound use and risk of autism spectrum disorder: Findings from the case-control Study to Explore Early Development.

BACKGROUND: Studies evaluating the association between prenatal ultrasounds and autism spectrum disorder (ASD) have largely produced negative results. Concern remains due to the rising identification of children with ASD and ultrasound use. OBJECTIVE: To evaluate the association between prenatal ultrasound use and ASD. METHODS: We used data from the Study to Explore Early Development, a multisite case-control study of preschool-aged children with ASD implemented during 2007-2012. We recruited cases from children receiving developmental disability services and randomly selected population controls from birth records. ASD case status was based on in-person standardised assessments. We stratified analyses by pre-existing maternal medical conditions and pregnancy complications associated with increased ultrasound use (ultrasound indications) and used logistic regression to model case status by increasing ultrasound counts. For pregnancies with medical record data on ultrasound timing, we conducted supplementary tests to model associations by trimester of exposure. RESULTS: Among 1524 singleton pregnancies, ultrasound indications were more common for ASD cases than controls; respectively, for each group, no indications were reported for 45.1% and 54.2% of pregnancies, while ≥2 indications were reported for 26.1% and 18.4% of pregnancies. The percentage of pregnancies with multiple ultrasounds varied by case status and the presence of ultrasound indications. However, stratified regression models showed no association between increasing ultrasound counts and case status, either for pregnancies without (aOR 1.01, 95% CI 0.92, 1.11) or with ultrasound indications (aOR 1.01, 95% CI 0.95, 1.08). Trimester-specific analyses using medical record data showed no association in any individual trimester. CONCLUSIONS: We found no evidence that prenatal ultrasound use increases ASD risk. Study strengths included gold-standard assessments for ASD case classification, comparison of cases with controls, and a stratified sample to account for conditions associated both with increased prenatal ultrasound use and ASD.

Maternal Smoking and Congenital Heart Defects, National Birth Defects Prevention Study, 1997-2011.

OBJECTIVES: To assess associations between maternal smoking and congenital heart defects (CHDs) in offspring. STUDY DESIGN: We performed a retrospective case-control study using data for cases of CHD (n = 8339) and nonmalformed controls (n = 11 020) from all years (1997-2011) of the National Birth Defects Prevention Study. Maternal self-reported smoking 1 month before through 3 months after conception was evaluated as a binary (none, any) and categorical (light, medium, heavy) exposure. Multivariable logistic regression was used to estimate aOR and 95% CIs. Stratified analyses were performed for septal defects according to maternal age, prepregnancy body mass index, and maternal race/ethnicity. RESULTS: Multiple CHDs displayed modest associations with any level of maternal periconceptional smoking independent of potential confounders; the strongest associations were for aggregated septal defects (OR, 1.5; 95% CI, 1.3-1.7), tricuspid atresia (OR, 1.7; 95% CI, 1.0-2.7), and double outlet right ventricle (DORV) (OR, 1.5; 95% CI, 1.1-2.1). Tricuspid atresia and DORV also displayed dose-response relationships. Among heavy smokers, the highest odds were again observed for tricuspid atresia (aOR 3.0; 95% CI, 1.5-6.1) and DORV (aOR 1.5; 95% CI, 1.1-2.2). Heavy smokers ≥35 years old more frequently had a child with a septal defect when compared with similarly aged nonsmokers (aOR 2.3; 95% CI, 1.4-3.9). CONCLUSIONS: Maternal periconceptional smoking is most strongly associated with septal defects, tricuspid atresia, and DORV; the risk for septal defects is modified by maternal age.

Evaluation of self-administered antigen testing in a college setting.

BACKGROUND: The objective of our investigation was to better understand barriers to implementation of self-administered antigen screening testing for SARS-CoV-2 at institutions of higher education (IHE). METHODS: Using the Quidel QuickVue At-Home COVID-19 Test, 1347 IHE students and staff were asked to test twice weekly for seven weeks. We assessed seroconversion using baseline and endline serum specimens. Online surveys assessed acceptability. RESULTS: Participants reported 9971 self-administered antigen test results. Among participants who were not antibody positive at baseline, the median number of tests reported was eight. Among 324 participants seronegative at baseline, with endline antibody results and ≥ 1 self-administered antigen test results, there were five COVID-19 infections; only one was detected by self-administered antigen test (sensitivity = 20%). Acceptability of self-administered antigen tests was high. CONCLUSIONS: Twice-weekly serial self-administered antigen testing in a low prevalence period had low utility in this investigation. Issues of testing fatigue will be important to address in future testing strategies.

Health Needs and Use of Services Among Children with Developmental Disabilities - United States, 2014-2018.

Developmental delays, disorders, or disabilities (DDs) manifest in infancy and childhood and can limit a person's function throughout life* (1-3). To guide strategies to optimize health for U.S. children with DDs, CDC analyzed data from 44,299 participants in the 2014-2018 National Health Interview Survey (NHIS). Parents reported on 10 DDs,† functional abilities, health needs, and use of services. Among the approximately one in six (17.3%) U.S. children and adolescents aged 3-17 years (hereafter children) with one or more DDs, 5.7% had limited ability to move or play, 4.7% needed help with personal care, 4.6% needed special equipment, and 2.4% received home health care, compared with ≤1% for each of these measures among children without DDs. Children with DDs were two to seven times as likely as those without DDs to have taken prescription medication for ≥3 months (41.6% versus 8.4%), seen a mental health professional (30.6% versus 4.5%), a medical specialist (26.0% versus 12.4%), or a special therapist, such as a physical, occupational, or speech therapist, (25.0% versus 4.5%) during the past year, and 18 times as likely to have received special education or early intervention services (EIS) (41.9% versus 2.4%). These percentages varied by type of disability and by sociodemographic subgroup. DDs are common, and children with DDs often need substantial health care and services. Policies and programs that promote early identification of children with developmental delays and facilitate increased access to intervention services can improve health and reduce the need for services later in life.§ Sociodemographic inequities merit further investigation to guide public health action and ensure early and equitable access to needed care and services.

Point-of-Care Antigen Test for SARS-CoV-2 in Asymptomatic College Students.

We used the BinaxNOW COVID-19 Ag Card to screen 1,540 asymptomatic college students for severe acute respiratory syndrome coronavirus 2 in a low-prevalence setting. Compared with reverse transcription PCR, BinaxNOW showed 20% overall sensitivity; among participants with culturable virus, sensitivity was 60%. BinaxNOW provides point-of-care screening but misses many infections.

Pilot Investigation of SARS-CoV-2 Secondary Transmission in Kindergarten Through Grade 12 Schools Implementing Mitigation Strategies - St. Louis County and City of Springfield, Missouri, December 2020.

Many kindergarten through grade 12 (K-12) schools offering in-person learning have adopted strategies to limit the spread of SARS-CoV-2, the virus that causes COVID-19 (1). These measures include mandating use of face masks, physical distancing in classrooms, increasing ventilation with outdoor air, identification of close contacts,* and following CDC isolation and quarantine guidance† (2). A 2-week pilot investigation was conducted to investigate occurrences of SARS-CoV-2 secondary transmission in K-12 schools in the city of Springfield, Missouri, and in St. Louis County, Missouri, during December 7-18, 2020. Schools in both locations implemented COVID-19 mitigation strategies; however, Springfield implemented a modified quarantine policy permitting student close contacts aged ≤18 years who had school-associated contact with a person with COVID-19 and met masking requirements during their exposure to continue in-person learning.§ Participating students, teachers, and staff members with COVID-19 (37) from 22 schools and their school-based close contacts (contacts) (156) were interviewed, and contacts were offered SARS-CoV-2 testing. Among 102 school-based contacts who received testing, two (2%) had positive test results indicating probable school-based SARS-CoV-2 secondary transmission. Both contacts were in Springfield and did not meet criteria to participate in the modified quarantine. In Springfield, 42 student contacts were permitted to continue in-person learning under the modified quarantine; among the 30 who were interviewed, 21 were tested, and none received a positive test result. Despite high community transmission, SARS-CoV-2 transmission in schools implementing COVID-19 mitigation strategies was lower than that in the community. Until additional data are available, K-12 schools should continue implementing CDC-recommended mitigation measures (2) and follow CDC isolation and quarantine guidance to minimize secondary transmission in schools offering in-person learning.

Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: evidence from a hospital-based surveillance database.

BACKGROUND: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. METHODS: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson's chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20-34 years. RESULTS: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06-1.23), low birth weight (aOR: 1.46; CI 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12-9.13) compared to mothers 20-34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7-14.3) was statistically significant when compared to mothers 20-34 years (1.6 per 10,000 births; 95% CI 0.9-2.6). CONCLUSIONS: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20-34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.

Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12­19 years) and mothers (age 20­34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20­34 years). Adolescent mothers were more likely than mothers (20­34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20­34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20­34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.

Pregnancy Outcomes among Women Receiving rVSVΔ-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola.

Little information exists regarding Ebola vaccine rVSVΔG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

Specific birth defects in pregnancies of women with diabetes: National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Diabetes is associated with an increased risk for many birth defects and is likely to have an increasing impact on birth defect prevalence because of the rise in diabetes in the United States in recent decades. One of the first analyses in which specific birth defects were assessed for their relationship with both pregestational and gestational diabetes used data from the initial 6 years of the National Birth Defects Prevention Study. That analysis reported strong associations for pregestational diabetes with several birth defects, but few exposures among some of the less common birth defects led to unstable estimates with wide confidence intervals. Since that analysis, the study continued to collect data for another 8 years, including information on approximately 19,000 additional cases and 6900 additional controls. OBJECTIVE: Our objective was to use data from the National Birth Defects Prevention Study, the largest population-based birth defects case-control study in the United States, to provide updated and more precise estimates of the association between diabetes and birth defects, including some defects not previously assessed. STUDY DESIGN: We analyzed data on deliveries from October 1997 through December 2011. Mothers of case and control infants were interviewed about their health conditions and exposures during pregnancy, including diagnosis of pregestational (type 1 or type 2) diabetes before the index pregnancy or gestational diabetes during the index pregnancy. Using logistic regression, we separately assessed the association between pregestational and gestational diabetes with specific categories of structural birth defects for which there were at least 3 exposed case infants. For birth defect categories for which there were at least 5 exposed case infants, we calculated odds ratios adjusted for maternal body mass index, age, education, race/ethnicity, and study site; for defect categories with 3 or 4 exposed cases, we calculated crude odds ratios. RESULTS: Pregestational diabetes was reported by 0.6% of mothers of control infants (71 of 11,447) and 2.5% of mothers of case infants (775 of 31,007). Gestational diabetes during the index pregnancy was reported by 4.7% of mothers of control infants (536 of 11,447) and 5.3% of mothers of case infants (1,653 of 31,007). Pregestational diabetes was associated with strong, statistically significant odds ratios (range, 2.5-80.2) for 46 of 50 birth defects considered. The largest odds ratio was observed for sacral agenesis (adjusted odds ratio, 80.2; 95% confidence interval, 46.1-139.3). A greater than 10-fold increased risk was also observed for holoprosencephaly (adjusted odds ratio, 13.1; 95% confidence interval, 7.0-24.5), longitudinal limb deficiency (adjusted odds ratio, 10.1; 95% confidence interval, 6.2-16.5), heterotaxy (adjusted odds ratio, 12.3; 95% confidence interval, 7.3-20.5), truncus arteriosus (adjusted odds ratio, 14.9; 95% confidence interval, 7.6-29.3), atrioventricular septal defect (adjusted odds ratio, 10.5; 95% confidence interval, 6.2-17.9), and single ventricle complex (adjusted odds ratio, 14.7; 95% confidence interval, 8.9-24.3). For gestational diabetes, statistically significant odds ratios were fewer (12 of 56) and of smaller magnitude (range, 1.3- 2.1; 0.5 for gastroschisis). CONCLUSION: Pregestational diabetes is associated with a markedly increased risk for many specific births defects. Because glycemic control before pregnancy is associated with a reduced risk for birth defects, ongoing quality care for persons with diabetes is an important opportunity for prevention.

Neural Tube Defects in Pregnancies Among Women With Diagnosed HIV Infection - 15 Jurisdictions, 2013-2017.

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

Periconceptional stressors and social support and risk for adverse birth outcomes.

BACKGROUND: The prevalence of preterm birth and low birth weight has been increasing slightly in recent years. A few studies have suggested that psychosocial stress during pregnancy may increase risk for these adverse birth outcomes. To extend those observations, we analyzed various major life event stressors separately and cumulatively as potential risk factors for preterm birth and low birth weight using granular categories of each outcome in a large, population-based study. Additionally, we assessed if greater social support buffered any effects. METHODS: Data were from a nested prevalence study of 4395 women in the National Birth Defects Prevention Study who delivered live-born non-malformed infants (controls) between 2006 and 2011. Participants completed a standardized, computer-assisted interview between 6 weeks and 24 months after delivery that included questions on stress and social support from 3 months before pregnancy to the 3rd month of pregnancy. Cumulative stress and support indices were also calculated. Preterm birth was divided into "early preterm" (< 32 weeks), "late preterm" (32-36 weeks) and "term." Low birthweight was divided into "very low birth weight" (< 1500 g), "low birth weight" (1500-2499 g) and "normal birth weight" (≥2500 g). Relative risks and 95% confidence intervals (95% CI) were calculated using Poisson regression. RESULTS: For women reporting relationship difficulties, there was a suggestive risk of early preterm birth (RR: 1.9, 95%CI: 0.9-3.9) and very low birthweight (RR: 2.0, 95%CI: 0.9-4.4). For women reporting that they or someone close to them were victims of abuse, violence, or crime, there was an increased risk of low birthweight (RR: 1.8, 95%CI: 1.1-2.7) and late preterm birth (RR: 1.5, 95%CI: 1.0-2.2). There were no strong associations observed between social support questions and the various outcomes. CONCLUSIONS: Our results add some support to prior evidence that certain stressors may be associated with increase selected adverse birth outcomes risk. We did not find strong evidence that social support buffered the observed risks in our study.

One-Carbon Cofactor Intake and Risk of Neural Tube Defects Among Women Who Meet Folic Acid Recommendations: A Multicenter Case-Control Study.

We aimed to investigate associations between individual and concurrent (≥2) intakes of one-carbon cofactors vitamins B6 and B12, choline, betaine, and methionine and neural tube defect (NTD) outcomes among mothers meeting the folic acid recommendations. In the Slone Birth Defects Study (case-control design; North America, 1998-2015), mothers of 164 NTD cases and 2,831 nonmalformed controls completed food frequency questionnaires and structured interviews. Estimated intakes of one-carbon cofactors were dichotomized (high vs. low) for all except betaine (low or middle vs. high). We used logistic regression models to estimate odds ratios and 95% confidence intervals adjusted for center, age, and race. The analysis was restricted to mothers with estimated daily total folate intake of ≥400 µg during periconception. Fewer cases, compared with controls, had high intakes for each one-carbon cofactor except betaine, where the starkest contrast occurred in the middle group. Women with concurrent high intakes of B6, B12, choline, and methionine and moderate intake of betaine had approximately half the risk of an NTD-affected pregnancy (odds ratio = 0.49, 95% confidence interval: 0.23, 1.08). These findings suggest that, in the presence of folic acid, one-carbon cofactors-notably when consumed together-might reduce NTD risk. Additional research should inform any changes to clinical recommendations.

Potential risk factors for Ebstein anomaly, National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Ebstein anomaly is a rare congenital heart defect (CHD) that, when severe, requires corrective surgery or other catheter-based intervention in the first year of life. Due to its rarity, risk factors for Ebstein anomaly remain largely unknown. Using national data, we examined 18 potential risk factors for Ebstein anomaly. METHODS: Using 1997-2011 data from the National Birth Defects Prevention Study, a population-based case-control study, we calculated crude and adjusted odds ratios and 95% confidence intervals for paternal age, maternal socio-demographics, reproductive history, and modifiable risk factors, and infant characteristics reported by mothers of 135 Ebstein anomaly cases and 11,829 controls. RESULTS: Mothers of Ebstein anomaly cases had 4.1 (95% confidence interval: 1.8, 9.5) times the odds of reporting a family history of CHD compared with mothers of controls. Ebstein anomaly was associated with maternal second-hand cigarette smoke exposure at home (odds ratio = 2.2 [95% confidence interval: 1.1, 4.4]), but not maternal cigarette smoking (odds ratio = 1.3 [95% confidence interval: 0.8, 2.1]). Odds were elevated, but the 95% confidence interval included 1.0, for maternal marijuana use (odds ratio = 1.8 [95% confidence interval: 0.9, 3.8]) and paternal age ≥40 years at delivery (odds ratio = 1.9 [95% confidence interval: 1.0, 3.5]). CONCLUSIONS: Maternal exposure to second-hand cigarette smoke at home and a family history of CHD were associated with elevated odds of Ebstein anomaly. Genetic analyses could clarify the potential heritability of Ebstein anomaly.

Proportion of Orofacial Clefts Attributable to Recognized Risk Factors.

OBJECTIVE: Estimate the population attributable fraction (PAF) for a set of recognized risk factors for orofacial clefts. DESIGN: We used data from the National Birth Defects Prevention Study. For recognized risk factors for which data were available, we estimated crude population attributable fractions (cPAFs) to account for potential confounding, average-adjusted population attributable fractions (aaPAFs). We assessed 11 modifiable and 3 nonmodifiable parental/maternal risk factors. The aaPAF for individual risk factors and the total aaPAF for the set of risk factors were calculated using a method described by Eide and Geffler. SETTING: Population-based case-control study in 10 US states. PARTICIPANTS: Two thousand seven hundred seventy-nine cases with isolated cleft lip with or without cleft palate (CL±P), 1310 cases with isolated cleft palate (CP), and 11 692 controls with estimated dates of delivery between October 1, 1997, and December 31, 2011. MAIN OUTCOME MEASURES: Crude population attributable fraction and aaPAF. RESULTS: The proportion of CL±P and CP cases attributable to the full set of examined risk factors was 50% and 43%, respectively. The modifiable factor with the largest aaPAF was smoking during the month before pregnancy or the first month of pregnancy (4.0% for CL±P and 3.4% for CP). Among nonmodifiable factors, the factor with the largest aaPAF for CL±P was male sex (27%) and for CP it was female sex (16%). CONCLUSIONS: Our results may inform research and prevention efforts. A large proportion of orofacial cleft risk is attributable to nonmodifiable factors; it is important to better understand the mechanisms involved for these factors.

Attention-Deficit/Hyperactivity Disorder Medication Prescription Claims Among Privately Insured Women Aged 15-44 Years - United States, 2003-2015.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects individuals across the lifespan. ADHD medication use among pregnant women is increasing (1), but consensus about the safety of ADHD medication use during pregnancy is lacking. Given that nearly half of U.S. pregnancies are unintended (2), and early pregnancy is a critical period for fetal development, examining trends in ADHD medication prescriptions among reproductive-aged women is important to quantify the population at risk for potential exposure. CDC used the Truven Health MarketScan Commercial Database* for the period 2003-2015 to estimate the percentage of women aged 15-44 years with private employer-sponsored insurance who filled prescriptions for ADHD medications each year. The percentage of reproductive-aged women who filled at least one ADHD medication prescription increased 344% from 2003 (0.9% of women) to 2015 (4.0% of women). In 2015, the most frequently filled medications were mixed amphetamine salts, lisdexamfetamine, and methylphenidate. Prescribing ADHD medications to reproductive-aged women is increasingly common; additional research on ADHD medication safety during pregnancy is warranted to inform women and their health care providers about any potential risks associated with ADHD medication exposure before and during pregnancy.

Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia.

We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

Inpatient Hospitalization Costs Associated with Birth Defects Among Persons of All Ages - United States, 2013.

In the United States, major structural or genetic birth defects affect approximately 3% of live births (1) and are responsible for 20% of infant deaths (2). Birth defects can affect persons across their lifespan and are the cause of significant lifelong disabilities. CDC used the Healthcare Cost and Utilization Project (HCUP) 2013 National Inpatient Sample (NIS), a 20% stratified sample of discharges from nonfederal community hospitals, to estimate the annual cost of birth defect-associated hospitalizations in the United States, both for persons of all ages and by age group. Birth defect-associated hospitalizations had disproportionately high costs, accounting for 3.0% of all hospitalizations and 5.2% of total hospital costs. The estimated annual cost of birth defect-associated hospitalizations in the United States in 2013 was $22.9 billion. Estimates of the cost of birth defect-associated hospitalizations offer important information about the impact of birth defects among persons of all ages on the overall health care system and can be used to prioritize prevention, early detection, and care.

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.