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Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Danielle M. Zerr reports institutional support from Merck and consulting fees from AlloVir. Melissa S. Stockwell reports institutional support from the National Institutes of Health (NIH). Mary Allen Staat reports institutional support from NIH, Pfizer, Cepheid, and Merck and receipt of royalties from UpToDate for chapters on adoption and immunization. Jennifer E. Schuster reports institutional support from NIH, the Food and Drug Administration, and the State of Missouri, receipt of an honorarium from the Missouri chapter of the American Academy of Pediatrics (AAP) and participation on the advisory board of the Association of American Medical Colleges and the Association for Professionals in Infection Control and Epidemiology. Adrienne G. Randolph reports institutional support from NIH, royalties for UpToDate for work as a section editor, consulting fees from Inotrem, Inc. and ThermoFisher, Inc., receipt of honoraria from St. Jude Children’s Research Center and Volition, Inc., travel support from the International Sepsis Forum, participation on a data safety monitoring board for NIH and the Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia, serving as chair (2023–2024) of the International Sepsis Forum, and receipt of equipment from Illumina, Inc. (for institutional use). Pia S. Pannaraj reports institutional support from the National Institute on Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, and AstraZeneca, receipt of honoraria from IDweek and Infectious Diseases in Children Symposium, payment for expert testimony from BBV Law Firm and Helsell Fetterman Law Firm, waiver of registration fee for IDweek meeting, uncompensated participation on three data safety monitoring boards 1) Phase II, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial to Assess the Safety, Reactogenicity and Immunogenicity of One or Two Doses of Multimeric-001 (M-001) Followed by One or Two Doses of an Influenza A/H7N9 Vaccine, 2) Therapeutic Fecal Transplant on the Gut Microbiome in Children with Ulcerative Colitis, and 3) Safety of Fecal Transplant in maintenance of pediatric Crohn's disease), and uncompensated services as president of the California Immunization Coalition and the AAP Committee on Infectious Diseases. Kanokporn Mongkolrattanothai reports institutional support from Gilead. Samina S. Bhumbra reports travel support from CDC to present a plenary lecture at the Conference on Emerging Infectious Diseases. Kathleen Chiotos reports institutional support from the Agency for Healthcare Research and Quality and travel support from IDWeek (2022), Society for Healthcare Epidemiology of America (2022), and Pediatric Academic Societies (2022). Bria M. Coates reports institutional support from the National Heart, Lung, and Blood Institute and the American Lung Association, payment for expert testimony from Triplett Woolf Garretson, and participation on a Sobi Data Safety Monitoring Board. Thomas J. Connors reports grant support from NIH. Melissa L. Cullimore reports institutional support from NIH. Heidi R. Flori reports receipt of consulting fees from Lucira Health for advisory role for rapid diagnostic devices for COVID-19. Shira J. Gertz reports ownership of Pfizer stock. Ivan Gonzalez reports receipt of honoraria from the Florida Chapter of AAP for educational infection control initiatives and travel support from the Florida Chapter of AAP for regional conference attendance. Judith A. Guzman-Cottrill reports receipt of a consulting contract from the Oregon Health Authority. Natasha B. Halasa reports receipt of investigator-initiated grants from Sanofi, Quidel, and Merck. Charlotte V. Hobbs reports receipt of consulting fees from Dynamed.com and royalties as a content reviewer for UpToDate.com. Janet R. Hume reports institutional support from NIH and uncompensated participation on a data safety monitoring board for a study at the University of Minnesota (Magnesium sulfate as adjuvant analgesia and its effect on opiate use by postoperative transplant patients in the pediatric intensive care unit). Satoshi Kamidani reports institutional support from NIH, Pfizer, Moderna, Meissa, and Bavarian Nordic and receipt of honoraria from AAP. Michele Kong reports institutional support from NIH and uncompensated service on the Board of Directors for Jefferson County Department of Health, Callahan Eye Hospital, University of Alabama at Birmingham, and KultureCity. Regina M. Simeone reports payments received by her spouse from a previously managed Pfizer investment, which was sold in April 2023. No other potential conflicts of interest were disclosed.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No conflicts of interest were disclosed.

Objectives: Estimates of vaccination coverage during pregnancy and identification of disparities in vaccination coverage can inform vaccination campaigns and programs. We reported the prevalence of being offered or told to get the influenza vaccine by a health care provider (hereinafter, provider); influenza vaccination coverage during the 12 months before delivery; and tetanus, diphtheria, and acellular pertussis (Tdap) vaccination coverage during pregnancy among women with a recent live birth in the United States., Methods: We analyzed 2020 data from the Pregnancy Risk Assessment Monitoring System from 42 US jurisdictions (n = 41 673). We estimated the overall prevalence of being offered or told to get the influenza vaccine by a provider and influenza vaccination coverage during the 12 months before delivery. We estimated Tdap vaccination coverage during pregnancy from 21 jurisdictions with available data (n = 22 020) by jurisdiction and select characteristics., Results: In 2020, 84.9% of women reported being offered or told to get the influenza vaccine, and 60.9% received it, ranging from 35.0% in Puerto Rico to 79.7% in Massachusetts. Influenza vaccination coverage was lower among women who were not offered or told to get the influenza vaccine (21.4%) than among women who were offered or told to get the vaccine (68.1%). Overall, 72.7% of women received the Tdap vaccine, ranging from 52.8% in Mississippi to 86.7% in New Hampshire. Influenza and Tdap vaccination coverage varied by all characteristics examined., Conclusions: These results can inform vaccination programs and strategies to address disparities in vaccination coverage during pregnancy and may inform vaccination efforts for other infectious diseases among pregnant women., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Titilope Oduyebo is currently employed by Moderna, Cambridge, Massachusetts.

Background and Objectives: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19., Methods: We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]., Results: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died., Conclusions: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We investigated maternal COVID-19 related experiences during delivery hospitalizations, and whether experiences differed by maternal race and ethnicity., Study Design: Data from the Pregnancy Risk Assessment Monitoring System among women with live births between April-December 2020 were used. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) estimated associations between maternal race and ethnicity and COVID-19 related delivery experiences., Results: Among 12,879 women, 3.6% reported infant separation and 1.8% reported not being allowed support persons. Compared with non-Hispanic White women, American Indian/Alaska Native (AI/AN) (aPR = 2.7; CI: 1.2-6.2), Hispanic (aPR = 2.2; CI: 1.5-3.1), non-Hispanic Black (aPR = 2.4; CI: 1.7-3.6), and non-Hispanic Asian (aPR = 2.8; CI: 1.6-4.9) women reported more infant separation due to COVID-19. Not being allowed support persons was more common among AI/AN (aPR = 5.2; CI: 1.8-14.8) and non-Hispanic Black (aPR = 2.3; CI: 1.3-4.1) women., Conclusions: COVID-19 related delivery hospitalization experiences were unequally distributed among racial and ethnic minorities., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To examine the relationship between coronavirus disease 2019 (COVID-19) diagnosis at delivery and adverse maternal health and pregnancy outcomes during pre-Delta, Delta, and Omicron variant predominance, with a focus on the time period of Omicron variant predominance., Methods: We conducted a cross-sectional observational study with data from delivery hospitalizations in the Premier Healthcare Database from February 2020 to August 2023. The pre-Delta (February 2020-June 2021), Delta (July 2021-December 2021), and Omicron (January 2022-August 2023) periods of variant predominance were examined. Exposure to COVID-19 was identified by having a diagnostic code for COVID-19 during the delivery hospitalization. Adjusted prevalence ratios (aPRs) were calculated to compare the risks of adverse maternal and pregnancy outcomes for women with and without COVID-19 diagnoses at the time of delivery for each variant period., Results: Among 2,990,973 women with delivery hospitalizations, 1.9% (n=56,618) had COVID-19 diagnoses noted at delivery admission discharge, including 26,053 during the Omicron period. Across all variant time periods, the prevalence of many adverse maternal and pregnancy outcomes during the delivery hospitalization was significantly higher for pregnant women with COVID-19 compared with pregnant women without COVID-19. In adjusted models, COVID-19 during the Omicron period was associated with significant increased risks for maternal sepsis (COVID-19: 0.4% vs no COVID-19: 0.1%; aPR 3.32, 95% CI, 2.70-4.08), acute respiratory distress syndrome (0.6% vs 0.1%; aPR 6.19, 95% CI, 5.26-7.29), shock (0.2% vs 0.1%; aPR 2.14, 95% CI, 1.62-2.84), renal failure (0.5% vs 0.2%; aPR 2.08, 95% CI, 1.73-2.49), intensive care unit admission (2.7% vs 1.7%; aPR 1.64, 95% CI, 1.52-1.77), mechanical ventilation (0.3% vs 0.1%; aPR 3.15, 95% CI, 2.52-3.93), in-hospital death (0.03% vs 0.01%; aPR 5.00, 95% CI, 2.30-10.90), stillbirth (0.7% vs 0.6%; aPR 1.17, 95% CI, 1.01-1.36), and preterm delivery (12.3% vs 9.6%; aPR 1.28, 95% CI, 1.24-1.33)., Conclusion: Despite the possibility of some level of immunity due to previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or testing differences, risks of adverse outcomes associated with COVID-19 diagnosis at delivery remained elevated during the Omicron variant time period., Competing Interests: Financial Disclosure Regina M. Simeone disclosed previously owning Pfizer stock. Jeffrey Carlson disclosed previously owning Moderna stock. Laura Riley disclosed being an author for Up to Date (HSV, Rubella, Parvovirus), consultant to GSK and Pfizer, and consulted on Medscape education module. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Pregnant, postpartum, and lactating people, and infants have unique needs during public health emergencies, including nuclear and radiological incidents. This report provides information on the CDC Division of Reproductive Health's emergency preparedness and response activities to address the needs of women of reproductive age (aged 15-49 years), people who are pregnant, postpartum, or lactating, and infants during a radiation emergency. Highlighted preparedness activities include: (1) development of a quick reference guide to inform key questions about pregnant, postpartum, and lactating people, and infants during radiation emergencies; and (2) exercising the role of reproductive health experts during nuclear and radiological incident preparedness activities.

Objective: Exposure to natural disasters during and after pregnancy may increase adverse mental health outcomes. Hurricanes Irma and Maria struck Puerto Rico in September 2017. Our objectives were to understand hurricane-related experiences, maternal health concerns, and the impact of hurricane experiences on postpartum depressive symptoms (PDS)., Methods: We used data from the 2018 Pregnancy Risk Assessment Monitoring System to describe differences in maternal hurricane experiences among women who were pregnant during and after the 2017 hurricanes. We assessed maternal concerns and PDS. We estimated adjusted prevalence ratios (aPRs) and 95% CIs for the associations between hurricane experiences and PDS., Results: The most frequently reported hurricane experiences were losing power for ≥1 week (97%) and feeling unsafe due to lack of order/security (70%). Almost 30% of women who were pregnant during the hurricanes reported missing prenatal care. PDS were reported by 13% of women. Most hurricane experiences were associated with an increased prevalence of PDS. Feeling unsafe (aPR = 2.4; 95% CI, 1.2-4.9) and having difficulty getting food (aPR = 2.1; 95% CI, 1.1-4.1) had the strongest associations., Conclusions: Most women who were pregnant during or after hurricanes Irma and Maria struck Puerto Rico reported negative hurricane experiences, and most experiences were associated with an increased prevalence of PDS. Understanding the experiences of pregnant women during and after disasters and identifying risks for adverse mental health outcomes after pregnancy are important to inform emergency preparedness and prenatal and postpartum care., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Regina M. Simeone reports payments received by her spouse from a previously managed Pfizer investment, which was sold in April 2023. Natasha Halasa reports grant support from Sanofi, Quidel, and Merck, and testing and vaccine donation for Sanofi; and an education grant for delivering a lecture. Satoshi Kamidani reports institutional support from the National Institutes of Health (NIH), Pfizer, Meissa, and Emergent BioSolutions; and honoraria from the American Academy of Pediatrics (AAP). Pia S. Pannaraj reports institutional support from AstraZeneca and NIH, payment for expert testimony, and unpaid service on the AAP’s Committee on Infectious Diseases and the California Immunization Coalition. Aline B. Maddux reports support from the International Severe Acute Respiratory and Emerging Infections Consortium for conference attendance. Charlotte V. Hobbs reports receipt of consulting fees from Dynamed.com for review of a clinical database and honoraria from bioMérieux for speaking at Biofire (bioMérieux) 2022. Julie A. Boom reports receipt of royalties from UpToDate, Inc. for chapter authorship. Michele Kong reports institutional support from NIH and KultureCity board membership. Jennifer E. Schuster reports institutional support from NIH and the Food and Drug Administration, consulting fees from the Association for Professionals in Infection Control and Epidemiology and the Association of American Medical Colleges, and honoraria from the Missouri American Academy of Pediatrics. Janet R. Hume reports institutional support from the National Institute of Child Health and Human Development and NIH, consulting fees from Entegrion, and uncompensated service on a data safety managing board for an institutional study at the University of Minnesota. Mary A. Staat reports institutional support from NIH, Merck, and Cepheid, and royalties from UpToDate, Inc. for unrelated subject matter. Emily R. Levy reports institutional support from the National Institute on Allergy and Infectious Diseases and consulting fees from the Health Resources and Service Administration Regional Pediatric Pandemic Network. Heidi R. Flori reports consulting fees from NOTA Laboratories and Lucira Health, unrelated to the current work; housing compensation from the Society of Critical Care Medicine for participation in the Pediatric Surviving Sepsis Campaign; and unfunded participation on a data safety monitory board for normoxia in cardiothoracic surgery and cyclodextrin in Niemann-Pick disease. Adrienne G. Randolph reports grant support from NIH for work related to COVID-19, royalties from UpToDate, Inc. for work as the Pediatric Critical Care Medicine section editor; honoraria from grand rounds presentations on multisystem inflammatory syndrome in children and sepsis; meeting attendance support from the International Sepsis Forum, participation on a data safety monitoring board for the NIH Grace Study; chair of the Families Fighting Flu International Sepsis Forum medical advisory board; and receipt of reagents from Illumina, Inc. No other potential conflicts of interest were disclosed.

We report healthcare provider attitudes and practices on emergency preparedness counseling for women of reproductive age (WRA), including pregnant, postpartum, and lactating women (PPLW), for disasters and weather emergencies. DocStyles is a web-based panel survey of primary healthcare providers in the United States. During March 17-May 17, 2021, obstetricians-gynecologists, family practitioners, internists, nurse practitioners, and physician assistants were asked about the importance of emergency preparedness counseling, level of confidence, frequency, barriers to providing counseling, and preferred resources to support counseling among WRA and PPLW. We calculated frequencies of provider attitudes and practices, and prevalence ratios with 95% CIs for questions with binary responses. Among 1503 respondents (family practitioners (33%), internists (34%), obstetrician-gynecologists (17%), nurse practitioners (8%), and physician assistants (8%)), 77% thought emergency preparedness was important, and 88% thought counseling was necessary for patient health and safety. However, 45% of respondents did not feel confident providing emergency preparedness counseling, and most (70%) had never talked to PPLW about this topic. Respondents cited not having time during clinical visits (48%) and lack of knowledge (34%) as barriers to providing counseling. Most respondents (79%) stated they would use emergency preparedness educational materials for WRA, and 60% said they were willing to take an emergency preparedness training. Healthcare providers have opportunities to provide emergency preparedness counseling; however, many have not, noting lack of time and knowledge as barriers. Emergency preparedness resources combined with training may improve healthcare provider confidence and increase delivery of emergency preparedness counseling., Competing Interests: Declaration of Competing Interest The authors declare they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

First trimester entry into prenatal care is recommended for all women, and especially women with pre-pregnancy conditions. Our objective was to determine whether women with pre-pregnancy conditions were at lower risk of entry after the first trimester (delayed entry) into prenatal care than women without a pre-pregnancy health condition. We used data from 10,890 participants in the National Birth Defects Prevention Study who delivered liveborn infants without birth defects. Women reported pre-pregnancy conditions and timing of entry into prenatal care during a computer-assisted telephone interview. Multivariable logistic regression analyses were conducted to evaluate whether having a pre-pregnancy condition was associated with delayed entry into prenatal care compared to women without pre-pregnancy conditions. Approximately 13% of women reported delayed entry into prenatal care, and 18% of women reported a pre-pregnancy condition. Delayed entry into prenatal care was not associated with pre-pregnancy cardiometabolic or neurologic conditions. Women with thyroid conditions were less likely to report delayed entry into prenatal care (prevalence odds ratio (OR), 95% confidence interval (CI): 0.55 [0.32, 0.94]), but women with hematologic and respiratory conditions were more likely to report delayed entry into prenatal care (OR: 1.95 [1.00, 3.82] and 1.27 [0.95, 1.72], respectively), compared to those without any chronic conditions. Future research investigating the success of early prenatal care among women with thyroid conditions could identify ways to reduce delayed prenatal care among women with other pre-pregnancy conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Objective: Our objective was to assess differences in pregnancy outcomes during the COVID-19 pandemic compared to the previous year., Study Design: In a cross-sectional study of delivery hospitalizations in the Premier Healthcare Database Special COVID-19 Release, we assessed differences in selected maternal and pregnancy outcomes occurring April-December in 2019 and 2020 in the United States., Result: Among 663,620 deliveries occurring in 2019 and 614,093 deliveries occurring in 2020, we observed an increase in in-hospital maternal death from 2019 to 2020, which was no longer statistically significant after excluding deliveries with a COVID-19 diagnosis. Intensive care unit admission and preterm birth decreased from 2019 to 2020. There was no difference in the prevalence of most other outcomes examined., Conclusion: The full impact of the COVID-19 pandemic on maternal and pregnancy outcomes remains to be understood. Most outcomes investigated experienced minimal change from 2019 to 2020., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Due to invasive treatments and stressors related to heart health, adults with congenital heart defects (CHDs) may have an increased risk of post-traumatic stress disorder (PTSD), anxiety, and/or depressive disorders. Our objectives were to estimate the prevalence of these disorders among individuals with CHDs., Methods: Using IBM® MarketScan® Databases, we identified adults age 18-49 years with ≥2 outpatient anxiety/depressive disorder claims on separate dates or ≥1 inpatient anxiety/depressive disorder claim in 2017. CHDs were defined as ≥2 outpatient CHD claims ≥30 days apart or ≥1 inpatient CHD claim documented in 2007-2017. We used log-binomial regression to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between CHDs and anxiety/depressive disorders., Results: Of 13,807 adults with CHDs, 12.4% were diagnosed with an anxiety or depressive disorder. Adults with CHDs, compared to the 5,408,094 without CHDs, had higher prevalence of PTSD (0.8% vs. 0.5%; aPR: 1.5 [CI: 1.2-1.8]), anxiety disorders (9.9% vs. 7.5%; aPR: 1.3 [CI: 1.3-1.4]), and depressive disorders (6.3% vs. 4.9%; aPR: 1.3 [CI: 1.2-1.4]). Among individuals with CHDs, female sex (aPR range: 1.6-3.3) and inpatient admission (aPR range 1.1-1.9) were associated with anxiety/depressive disorders., Conclusion: Over 1 in 8 adults with CHDs had diagnosed PTSD and/or other anxiety/depressive disorders, 30-50% higher than adults without CHDs. PTSD was rare, but three times more common in women with CHDs than men. Screening and referral for services for these conditions in people with CHDs may be beneficial., (© 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB-CBCL and PCB-WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pregnant women are at increased risk for severe COVID-19-related illness, and COVID-19 is associated with an increased risk for adverse pregnancy outcomes and maternal and neonatal complications (1-3). To date, studies assessing whether COVID-19 during pregnancy is associated with increased risk for stillbirth have yielded mixed results (2-4). Since the B.1.617.2 (Delta) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant,* there have been anecdotal reports of increasing rates of stillbirths in women with COVID-19. † CDC used the Premier Healthcare Database Special COVID-19 Release (PHD-SR), a large hospital-based administrative database, § to assess whether a maternal COVID-19 diagnosis documented at delivery hospitalization was associated with stillbirth during March 2020-September 2021 as well as before and during the period of Delta variant predominance in the United States (March 2020-June 2021 and July-September 2021, respectively). Among 1,249,634 deliveries during March 2020-September 2021, stillbirths were rare (8,154; 0.65%): 273 (1.26%) occurred among 21,653 deliveries to women with COVID-19 documented at the delivery hospitalization, and 7,881 (0.64%) occurred among 1,227,981 deliveries without COVID-19. The adjusted risk for stillbirth was higher in deliveries with COVID-19 compared with deliveries without COVID-19 during March 2020-September 2021 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.69-2.15), including during the pre-Delta (aRR = 1.47; 95% CI = 1.27-1.71) and Delta periods (aRR = 4.04; 95% CI = 3.28-4.97). COVID-19 documented at delivery was associated with increased risk for stillbirth, with a stronger association during the period of Delta variant predominance. Implementing evidence-based COVID-19 prevention strategies, including vaccination before or during pregnancy, is critical to reducing the impact of COVID-19 on stillbirths., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: Zika virus is primarily transmitted through mosquito bites. Because Zika virus infection during pregnancy can cause serious birth defects, reproductive-aged women need protection from Zika virus infection. This report describes Zika virus prevention behaviors among women aged 18-49 years and assesses whether pregnancy status and healthcare provider counseling increases Zika virus prevention behaviors., Methods: A population-based cell phone survey of women aged 18-49 years living in Puerto Rico was conducted in July-November 2016. Data were analyzed in 2018-2019. Prevalence estimates and 95% CIs were calculated for Zika virus prevention behaviors. Adjusted prevalence ratios were estimated to examine the association of pregnancy status with healthcare provider counseling on Zika virus prevention behaviors, controlling for age, education, and health insurance status., Results: Most women reported using screens on open doors/windows (87.7%) and eliminating standing water in/around their homes (92.3%). Other Zika virus prevention behaviors were less common (<33%). In adjusted analysis, pregnant women were more likely than women not at risk for unintended pregnancy to report using mosquito repellent every/most days (adjusted prevalence ratio=1.44, 95% CI=1.13, 1.85). Healthcare provider counseling was associated with receiving professional spraying/larvicide treatment (adjusted prevalence ratio=1.42, 95% CI=1.17, 1.74), sleeping under a bed net (adjusted prevalence ratio=2.37, 95% CI=1.33, 4.24), using mosquito repellent (adjusted prevalence ratio=1.57, 95% CI=1.40, 1.77), and wearing long sleeves/pants (adjusted prevalence ratio=1.32, 95% CI=1.12, 1.55)., Conclusions: Receipt of healthcare provider counseling was more consistently associated with Zika virus prevention behaviors than pregnancy status. Healthcare provider counseling is an important strategy for increasing the uptake of Zika virus prevention behaviors among women aged 18-49 years., (Published by Elsevier Inc.)

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., (© 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Evidence on risk for adverse outcomes from coronavirus disease 2019 (COVID-19) among pregnant women is still emerging. We examined the association between COVID-19 at delivery and adverse pregnancy outcomes, maternal complications, and severe illness, and whether these associations differ by race/ethnicity, and describe discharge status by COVID-19 diagnosis and maternal complications., Methods: Data from 703 hospitals in the Premier Healthcare Database during March-September 2020 were included. Adjusted risk ratios (aRRs) overall and stratified by race/ethnicity were estimated using Poisson regression with robust standard errors. Proportion not discharged home was calculated by maternal complications, stratified by COVID-19 diagnosis., Results: Among 489 471 delivery hospitalizations, 6550 (1.3%) had a COVID-19 diagnosis. In adjusted models, COVID-19 was associated with increased risk for acute respiratory distress syndrome (aRR, 34.4), death (aRR, 17.0), sepsis (aRR, 13.6), mechanical ventilation (aRR, 12.7), shock (aRR, 5.1), intensive care unit admission (aRR, 3.6), acute renal failure (aRR, 3.5), thromboembolic disease (aRR, 2.7), adverse cardiac event/outcome (aRR, 2.2), and preterm labor with preterm delivery (aRR, 1.2). Risk for any maternal complications or for any severe illness did not significantly differ by race/ethnicity. Discharge status did not differ by COVID-19; however, among women with concurrent maternal complications, a greater proportion of those with (vs without) COVID-19 were not discharged home., Conclusions: These findings emphasize the importance of implementing recommended prevention strategies to reduce risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and further inform counseling and clinical care for pregnant women during the COVID-19 pandemic., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015-2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.

Importance: Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks., Objective: To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions., Design, Setting, and Participants: The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection., Exposures: Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants., Main Outcomes and Measures: We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period., Results: This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12-53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83)., Conclusions and Relevance: We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.

Background In women with congenital heart defects (CHD), changes in blood volume, heart rate, respiration, and edema during pregnancy may lead to increased risk of adverse outcomes and conditions. The American Heart Association recommends providers of pregnant women with CHD assess cardiac health and discuss risks and benefits of cardiac-related medications. We described receipt of American Heart Association-recommended cardiac evaluations, filled potentially teratogenic or fetotoxic (Food and Drug Administration pregnancy category D/X) cardiac-related prescriptions, and adverse conditions among pregnant women with CHD compared with those without CHD. Methods and Results Using 2007 to 2014 US healthcare claims data, we ascertained a retrospective cohort of women with and without CHD aged 15 to 44 years with private insurance covering prescriptions during pregnancy. CHD was defined as ≥1 inpatient code or ≥2 outpatient CHD diagnosis codes >30 days apart documented outside of pregnancy and categorized as severe or nonsevere. Log-linear regression, accounting for multiple pregnancies per woman, generated adjusted prevalence ratios (aPRs) for associations between the presence/severity of CHD and stillbirth, preterm birth, and adverse conditions from the last menstrual period to 90 days postpartum. We identified 2056 women with CHD (2334 pregnancies) and 1 374 982 women without (1 524 077 pregnancies). During the last menstrual period to 90 days postpartum, 56% of women with CHD had comprehensive echocardiograms and, during pregnancy, 4% filled potentially teratogenic or fetotoxic cardiac-related prescriptions. Women with CHD, compared with those without, experienced more adverse conditions overall (aPR, 1.9 [95% CI, 1.7-2.1]) and, specifically, obstetric (aPR, 1.3 [95% CI, 1.2-1.4]) and cardiac conditions (aPR, 10.2 [95% CI, 9.1-11.4]), stillbirth (aPR, 1.6 [95% CI, 1.1-2.4]), and preterm delivery (aPR, 1.6 [95% CI, 1.4-1.8]). More women with severe CHD, compared with nonsevere, experienced adverse conditions overall (aPR, 1.5 [95% CI, 1.2-1.9]). Conclusions Women with CHD have elevated prevalence of adverse cardiac and obstetric conditions during pregnancy; 4 in 100 used potentially teratogenic or fetotoxic medications, and only half received an American Heart Association-recommended comprehensive echocardiogram.

Objectives: The objectives of this analysis were to 1) estimate prevalence of contraceptive use among women at risk for unintended pregnancy and 2) identify correlates of contraceptive use among women with ongoing or potential need for contraceptive services in Puerto Rico during the 2016 Zika virus (ZIKV) outbreak., Study Design: We conducted a cell-phone survey July-November, 2016. Women aged 18-49 years living in Puerto Rico were eligible. We completed 3059 interviews; the overall response rate was 69.2%. After weighting, the data provide population-based estimates. For this analysis, we included women at risk for unintended pregnancy, and assessed ongoing or potential need for contraceptive services in this group, excluding women using permanent contraceptive methods., Results: Most women reported using contraception (82.8%), and use increased with age. Female sterilization and male condoms were most frequently reported (40.8% and 17.1%, respectively). Among women with ongoing or potential need for contraceptive services, 24.7% talked to a healthcare provider about ZIKV, and 31.2% reported a change in childbearing intentions due to ZIKV. Most women were at least a little worried about getting infected with ZIKV (74.3%) or having a baby with a birth defect (80.9%). Being very worried about getting infected with ZIKV and already having Zika were significantly associated with use of any contraception (adjusted prevalence ratio: 1.19, 95% CI: 1.03-1.38 and 1.32, 95% CI: 1.01-1.72, respectively)., Conclusions: These findings underscore the need for regular contraceptive prevalence studies to inform programs about contraceptive needs, especially during public health emergencies., Implications: When the 2016 Zika virus outbreak began in Puerto Rico there were no recent population-based data available on contraceptive prevalence. To fill this information gap, we conducted a population-based survey. Our findings provided baseline contraceptive prevalence estimates to support response planning and allocation of health resources., (Published by Elsevier Inc.)

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., (Published by Elsevier Inc.)

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.

Ensuring access to and promoting use of effective contraception have been identified as important strategies for preventing unintended pregnancy (1). The importance of ensuring resources to prevent unintended pregnancy in the context of public health emergencies was highlighted during the 2016 Zika virus outbreak when Zika virus infection during pregnancy was identified as a cause of serious birth defects (2). Accordingly, CDC outlined strategies for state, local, and territorial jurisdictions to consider implementing to ensure access to contraception (3). To update previously published contraceptive use estimates* among women at risk for unintended pregnancy † and to estimate the number of women with ongoing or potential need for contraceptive services, § , ¶ data on contraceptive use were collected during September-December 2016 through the Behavioral Risk Factor Surveillance System (BRFSS). Results from 21 jurisdictions indicated that most women aged 18-49 years were at risk for unintended pregnancy (range across jurisdictions = 57.4%-76.8%). Estimates of the number of women with ongoing or potential need for contraceptive services ranged from 368 to 617 per 1,000 women aged 18-49 years. The percentage of women at risk for unintended pregnancy using a most or moderately effective contraceptive method** ranged from 26.1% to 65.7%. Jurisdictions can use this information to estimate the number of women who might seek contraceptive services and to plan and evaluate efforts to increase contraceptive use. This information is particularly important in the context of public health emergencies, such as the recent Zika virus outbreak, which have been associated with increased risk for adverse maternal-infant outcomes (2,4-6) and have highlighted the importance of providing women and their partners with resources to prevent unintended pregnancy., Competing Interests: No conflicts of interest were reported.

Zika virus infection can occur as a result of mosquitoborne or sexual transmission of the virus. Infection during pregnancy is a cause of fetal brain abnormalities and other serious birth defects (1,2). CDC has updated the interim guidance for men with possible Zika virus exposure who 1) are planning to conceive with their partner, or 2) want to prevent sexual transmission of Zika virus at any time (3). CDC now recommends that men with possible Zika virus exposure who are planning to conceive with their partner wait for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) before engaging in unprotected sex. CDC now also recommends that for couples who are not trying to conceive, men can consider using condoms or abstaining from sex for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) to minimize their risk for sexual transmission of Zika virus. All other guidance for Zika virus remains unchanged. The definition of possible Zika virus exposure remains unchanged and includes travel to or residence in an area with risk for Zika virus transmission (https://wwwnc.cdc.gov/travel/page/world-map-areas-with-zika) or sex without a condom with a partner who traveled to or lives in an area with risk for Zika virus transmission. CDC will continue to update recommendations as new information becomes available., Competing Interests: No conflicts of interest were reported.

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).

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.

Purpose: To assess the contribution of multiple risk factors for two congenital heart defects-hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF)., Methods: We used data from the National Birth Defects Prevention Study (1997-2011) to estimate average adjusted population attributable fractions for several recognized risk factors, including maternal prepregnancy overweight-obesity, pregestational diabetes, age, and infant sex., Results: There were 594 cases of isolated simple HLHS, 971 cases of isolated simple TOF, and 11,829 controls in the analysis. Overall, 57.0% of HLHS cases and 37.0% of TOF cases were estimated to be attributable to risk factors included in our model. Among modifiable HLHS risk factors, maternal prepregnancy overweight-obesity accounted for the largest proportion of cases (6.5%). Among modifiable TOF risk factors, maternal prepregnancy overweight-obesity and maternal age of 35 years or older accounted for the largest proportions of cases (8.3% and 4.3%, respectively)., Conclusions: Approximately half of HLHS cases and one-third of TOF cases were estimated to be attributable to risk factors included in our models. Interventions targeting factors that can be modified may help reduce the risk of HLHS and TOF development. Additional research into the etiology of HLHS and TOF may reveal other modifiable risk factors that might contribute to primary prevention efforts., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Health insurance claims are a rich data source to examine medication use in pregnancy. Our objective was to identify pregnant women, their pregnancy outcomes, and date of their last menstrual period (LMP), and to estimate antidepressant dispensations in pregnancy., Methods: From a literature search, we identified diagnosis and procedure codes indicating the end of a pregnancy. Using Truven Health MarketScan ® Commercial Claims and Encounters Databases, we identified all inpatient admissions and outpatient service claims with these codes. We developed an algorithm to assign: (1) pregnancy outcome (ectopic pregnancy, induced or spontaneous abortion, live birth, or stillbirth), and (2) estimated gestational age, to each inpatient or outpatient visit. For each pregnancy outcome, we estimated the LMP as the admission (for inpatient visits) or service (for outpatient visits) date minus the gestational age. To differentiate visits associated with separate pregnancies, we required ≥ 2 months between one pregnancy outcomes and the LMP of the next pregnancy. We used this algorithm to identify pregnancies in 2013 and to estimate the proportion of women who filled a prescription for an antidepressant from an outpatient pharmacy at various time points in pregnancy., Results: We identified 488,887 pregnancies in 2013; 79% resulted in a live birth. A prescription for an antidepressant was filled in 6.2% of pregnancies. Dispensations varied throughout pregnancy and were lowest (3.1%) during the second trimester., Conclusion: This work will inform future efforts to estimate medication dispensations during critical periods of preconception, interconception, and pregnancy using health insurance claims data. Birth Defects Research (Part A) 106:927-934, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Importance: Zika virus (ZIKV) infection during pregnancy is a cause of congenital microcephaly and severe fetal brain defects, and it has been associated with other adverse pregnancy and birth outcomes., Objective: To estimate the number of pregnant women infected with ZIKV in Puerto Rico and the number of associated congenital microcephaly cases., Design, Setting, and Participants: We conducted a modeling study from April to July 2016. Using parameters derived from published reports, outcomes were modeled probabilistically using Monte Carlo simulation. We used uncertainty distributions to reflect the limited information available for parameter values. Given the high level of uncertainty in model parameters, interquartile ranges (IQRs) are presented as primary results. Outcomes were modeled for pregnant women in Puerto Rico, which currently has more confirmed ZIKV cases than any other US location., Exposure: Zika virus infection in pregnant women., Main Outcomes and Measures: Number of pregnant women infected with ZIKV and number of congenital microcephaly cases., Results: We estimated an IQR of 5900 to 10 300 pregnant women (median, 7800) might be infected during the initial ZIKV outbreak in Puerto Rico. Of these, an IQR of 100 to 270 infants (median, 180) may be born with microcephaly due to congenital ZIKV infection from mid-2016 to mid-2017. In the absence of a ZIKV outbreak, an IQR of 9 to 16 cases (median, 12) of congenital microcephaly are expected in Puerto Rico per year., Conclusions and Relevance: The estimate of 5900 to 10 300 pregnant women that might be infected with ZIKV provides an estimate for the number of infants that could potentially have ZIKV-associated adverse outcomes. Including baseline cases of microcephaly, we estimated that an IQR of 110 to 290 total cases of congenital microcephaly, mostly attributable to ZIKV infection, could occur from mid-2016 to mid-2017 in the absence of effective interventions. The primary limitation in this analysis is uncertainty in model parameters. Multivariate sensitivity analyses indicated that the cumulative incidence of ZIKV infection and risk of microcephaly given maternal infection in the first trimester were the primary drivers of both magnitude and uncertainty in the estimated number of microcephaly cases. Increased information on these parameters would lead to more precise estimates. Nonetheless, the results underscore the need for urgent actions being undertaken in Puerto Rico to prevent congenital ZIKV infection and prepare for affected infants.

Background: Little population-based data exist on limitations and health-related quality of life (HRQoL) in adults with congenital heart defects (CHD)., Methods: We used 2004 to 2012 Medical Expenditure Panel Survey data to identify a population-based sample of young adults ages 18 to 40 years reporting health symptoms or healthcare encounters in the previous year. Comparing adults reporting CHD to others, we examined the prevalence of cognitive, physical, and activity limitations, depressive symptoms, and physical and mental HRQoL. We used chi square tests to examine differences in demographic characteristics, logistic regression to generate adjusted prevalence ratios (aPR), and linear regression to examine HRQoL. Multivariable associations were adjusted for sex, age, race/ethnicity, and smoking status. All analyses were conducted in SUDAAN using weights to account for clustering within sampling units and nonresponse., Results: Fifty-nine adults reported CHD (weighted prevalence = 0.1%; representing 700,000 U.S. adults from 2004 to 2012 or, on average, 80,000 per year) and 54,011 did not. No demographic characteristics differed significantly by CHD status except health insurance; 31.5% of adults with CHD, compared with 11.0% without, reported public insurance (p = 0.01). Compared with their counterparts, adults reporting CHD had a higher prevalence of cognitive (aPR = 2.7, 95% confidence interval (CI): 1.0, 7.2), physical (aPR = 4.0, 95% CI: 1.9, 8.2), and activity limitations (aPR = 4.8, 95% CI: 2.6, 9.1), and poorer physical HRQoL (p = 0.004). No differences were observed in depressive symptoms and mental HRQoL by CHD status., Conclusion: Physical health and cognitive abilities of adults with CHD were compromised compared with adults without CHD. Birth Defects Research (Part A) 106:580-586, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC's national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(†) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),(§) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women residing in Puerto Rico. As of May 12, 2016, the surveillance systems were monitoring 157 and 122 pregnant women with laboratory evidence of possible Zika virus infection from participating U.S. states and territories, respectively. Tracking and monitoring clinical presentation of Zika virus infection, all prenatal testing, and adverse consequences of Zika virus infection during pregnancy are critical to better characterize the risk for congenital infection, the performance of prenatal diagnostic testing, and the spectrum of adverse congenital outcomes. These data will improve clinical guidance, inform counseling messages for pregnant women, and facilitate planning for clinical and public health services for affected families.

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes, and symptoms of infection can include rash, fever, arthralgia, and conjunctivitis (1).* Zika virus infection during pregnancy is a cause of microcephaly and other severe brain defects (2). Infection has also been associated with Guillain-Barré syndrome (3). In December 2015, Puerto Rico became the first U.S. jurisdiction to report local transmission of Zika virus, with the index patient reporting symptom onset on November 23, 2015 (4). This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico. During November 1, 2015-April 14, 2016, a total of 6,157 specimens from suspected Zika virus-infected patients were evaluated by the Puerto Rico Department of Health (PRDH) and CDC Dengue Branch (which is located in San Juan, Puerto Rico), and 683 (11%) had laboratory evidence of current or recent Zika virus infection by one or more tests: reverse transcription-polymerase chain reaction (RT-PCR) or immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA). Zika virus-infected patients resided in 50 (64%) of 78 municipalities in Puerto Rico. Median age was 34 years (range = 35 days-89 years). The most frequently reported signs and symptoms were rash (74%), myalgia (68%), headache (63%), fever (63%), and arthralgia (63%). There were 65 (10%) symptomatic pregnant women who tested positive by RT-PCR or IgM ELISA. A total of 17 (2%) patients required hospitalization, including 5 (1%) patients with suspected Guillain-Barré syndrome. One (<1%) patient died after developing severe thrombocytopenia. The public health response to the outbreak has included increased laboratory capacity to test for Zika virus infection (including blood donor screening), implementation of enhanced surveillance systems, and prevention activities focused on pregnant women. Vector control activities include indoor and outdoor residual spraying and reduction of mosquito breeding environments focused around pregnant women's homes. Residents of and travelers to Puerto Rico should continue to employ mosquito bite avoidance behaviors, take precautions to reduce the risk for sexual transmission (5), and seek medical care for any acute illness with rash or fever.

The marked increase in infants born with microcephaly in Brazil after a 2015 outbreak of Zika virus (Zika virus) disease suggests an association between maternal Zika virus infection and congenital microcephaly. To project the timing of delivery of infants born to mothers infected during early pregnancy in 1 city in Bahia State, Brazil, we incorporated data on reported Zika virus disease cases and microcephaly cases into a graphical schematic of weekly birth cohorts. We projected that these births would occur through February 2016. Applying similar projections to a hypothetical location at which Zika virus transmission started in November, we projected that full-term infants at risk for Zika virus infection would be born during April-September 2016. We also developed a modifiable spreadsheet tool that public health officials and researchers can use for their countries to plan for deliveries of infants to women who were infected with Zika virus during different pregnancy trimesters.

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes. Increasing evidence links Zika virus infection during pregnancy to adverse pregnancy and birth outcomes, including pregnancy loss, intrauterine growth restriction, eye defects, congenital brain abnormalities, and other fetal abnormalities. The virus has also been determined to be sexually transmitted. Because of the potential risks associated with Zika virus infection during pregnancy, CDC has recommended that health care providers discuss prevention of unintended pregnancy with women and couples who reside in areas of active Zika virus transmission and do not want to become pregnant. However, limitations in access to contraception in some of these areas might affect the ability to prevent an unintended pregnancy. As of March 16, 2016, the highest number of Zika virus disease cases in the United States and U.S. territories were reported from Puerto Rico. The number of cases will likely rise with increasing mosquito activity in affected areas, resulting in increased risk for transmission to pregnant women. High rates of unintended and adolescent pregnancies in Puerto Rico suggest that, in the context of this outbreak, access to contraception might need to be improved. CDC estimates that 138,000 women of reproductive age (aged 15-44 years) in Puerto Rico do not desire pregnancy and are not using one of the most effective or moderately effective contraceptive methods, and therefore might experience an unintended pregnancy. CDC and other federal and local partners are seeking to expand access to contraception for these persons. Such efforts have the potential to increase contraceptive access and use, reduce unintended pregnancies, and lead to fewer adverse pregnancy and birth outcomes associated with Zika virus infection during pregnancy. The assessment of challenges and resources related to contraceptive access in Puerto Rico might be a useful model for other areas with active transmission of Zika virus.

Antidepressant medication use during pregnancy has been increasing in the United States (1). Many women require antidepressants on an ongoing basis, and a clear consensus on the safest medication options for both the mother and her fetus does not exist (2). Given that half of all U.S. pregnancies are unplanned (3), antidepressant use will occur during the first weeks of pregnancy, a critical period for fetal development. To understand trends among women of reproductive age, CDC used Truven Health's MarketScan Commercial Claims and Encounters data* to estimate the number of antidepressant prescriptions filled by women aged 15-44 years with private employer-sponsored insurance. During 2008-2013, an average of 15.4% of women aged 15-44 years filled at least one prescription for an antidepressant in a single year. The most frequently filled antidepressants included sertraline, bupropion, and citalopram. Prescribing of antidepressants is common, and research on antidepressant safety during pregnancy needs to be accelerated to provide evidence-based information to health care providers and women about the potential risks for antidepressant exposure before and during pregnancy and between pregnancies.

Major birth defects (birth defects) are defined as structural abnormalities, present at birth, with surgical, medical, or cosmetic importance. Each year in the United States, 3% of live births (approximately 120,000 infants) have an identifiable structural birth defect. Examples of birth defects include neural tube defects, such as spina bifida; orofacial clefts; abdominal wall defects, such as gastroschisis; and congenital heart defects, such as hypoplastic left heart syndrome. Collectively, congenital heart defects are the most common birth defects (27%), followed by musculoskeletal defects (18%), genitourinary defects (15%), orofacial defects (5%), and neural tube defects (2%).

Background: Congenital heart defects (CHDs) are common birth defects and are associated with high hospital costs. The objectives of this study were to assess hospitalization costs, across the lifespan, of patients with CHDs in Arkansas., Methods: Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were used. We included hospitalizations of patients whose admission occurred between January 1, 2006, and December 31, 2011, and included a principal or secondary CHD ICD-9-CM diagnosis code (745.0-747.49, except 747.0 and 745.5 for preterm infants). Hospitalizations were excluded if they involved out-of-state residents, normal newborn births, or if missing data included age at admission, state of residence, or hospital charges. Children were defined as those < 18 years-old at time of admission., Results: Between 2006 and 2011, there were 2,242,484 inpatient hospitalizations in Arkansas. There were 9071 (0.4%) hospitalizations with a CHD, including 5,158 hospitalizations of children (2.2% of hospitalizations among children) and 3,913 hospitalizations of adults (0.2% of hospitalizations of adults). Hospital costs for these CHD hospitalizations totaled $355,543,696. The average annual cost of CHD hospitalizations in Arkansas was $59,257,283 during this time period. Infants accounted for 72% of all CHD-related hospital costs; total costs of CHD hospitalizations for children were almost five times those of hospitalization costs for adults with CHD., Conclusion: Hospitalizations with CHDs account for a disproportionate share of hospital costs in Arkansas. Hospitalizations of children with CHD accounted for a higher proportion of total hospitalizations than did hospitalizations of adults with CHD., (© 2015 Wiley Periodicals, Inc.)

Background: Individuals with congenital heart defects (CHDs) have high hospital resource use. We sought to identify factors associated with hospital costs and multiple hospitalizations among individuals with CHDs., Methods: Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were linked across encrypted patient identifiers to develop a cohort of Arkansas residents aged 1 to 64 years who were hospitalized at least once with a CHD during this time period. Infants were excluded because patient identifiers were missing for 18 to 52% each year. CHDs were identified using principal and secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses codes. All hospitalizations of individuals ever admitted with a CHD were included. Mean and median patient-level costs were estimated; the association of hospital costs and patient readmissions were examined with linear and logistic regression., Results: There were 1,185,868 inpatient hospitalizations of Arkansas residents aged 1 to 64 years between 2006 and 2011; these were accrued by 603,925 patients. Of those, 2542 patients (0.42%) had at least one hospitalization with a CHD diagnosis. Total costs for these 2542 patients were $126,999,837 and they accumulated 7898 hospitalizations. Factors associated with increased costs included patient age, CHD type, cardiac procedures, and comorbidities. Factors associated with hospital readmission within 1 year included age, CHD type, expected payer, and comorbidities., Conclusion: Individuals with CHDs in Arkansas experience variation in hospital use and costs by patient characteristics. Future research should investigate factors associated with readmissions, cardiac procedures, and comorbidities, as these are strongly associated with hospital costs. Birth Defects Research (Part A) 103:589-596, 2015. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Context: Maternal pregestational diabetes (PGDM) is a risk factor for development of congenital heart defects (CHDs). Glycemic control before pregnancy reduces the risk of CHDs. A meta-analysis was used to estimate summary ORs and mathematical modeling was used to estimate population attributable fractions (PAFs) and the annual number of CHDs in the U.S. potentially preventable by establishing glycemic control before pregnancy., Evidence Acquisition: A systematic search of the literature through December 2012 was conducted in 2012 and 2013. Case-control or cohort studies were included. Data were abstracted from 12 studies for a meta-analysis of all CHDs., Evidence Synthesis: Summary estimates of the association between PGDM and CHDs and 95% credible intervals (95% CrIs) were developed using Bayesian random-effects meta-analyses for all CHDs and specific CHD subtypes. Posterior estimates of this association were combined with estimates of CHD prevalence to produce estimates of PAFs and annual prevented cases. Ninety-five percent uncertainty intervals (95% UIs) for estimates of the annual number of preventable cases were developed using Monte Carlo simulation. Analyses were conducted in 2013. The summary OR estimate for the association between PGDM and CHDs was 3.8 (95% CrI=3.0, 4.9). Approximately 2670 (95% UI=1795, 3795) cases of CHDs could potentially be prevented annually if all women in the U.S. with PGDM achieved glycemic control before pregnancy., Conclusions: Estimates from this analysis suggest that preconception care of women with PGDM could have a measureable impact by reducing the number of infants born with CHDs., (Published by Elsevier Inc.)

Background: Congenital heart defects (CHDs) occur in approximately 8 per 1000 live births. Improvements in detection and treatment have increased survival. Few national estimates of the healthcare costs for infants, children and adolescents with CHDs are available., Methods: We estimated hospital costs for hospitalizations using pediatric (0-20 years) hospital discharge data from the 2009 Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) for hospitalizations with CHD diagnoses. Estimates were up-weighted to be nationally representative. Mean costs were compared by demographic factors and presence of critical CHDs (CCHDs)., Results: Up-weighting of the KID generated an estimated 4,461,615 pediatric hospitalizations nationwide, excluding normal newborn births. The 163,980 (3.7%) pediatric hospitalizations with CHDs accounted for approximately $5.6 billion in hospital costs, representing 15.1% of costs for all pediatric hospitalizations in 2009. Approximately 17% of CHD hospitalizations had a CCHD, but it varied by age: approximately 14% of hospitalizations of infants, 30% of hospitalizations of patients aged 1 to 10 years, and 25% of hospitalizations of patients aged 11 to 20 years. Mean costs of CHD hospitalizations were higher in infancy ($36,601) than at older ages and were higher for hospitalizations with a CCHD diagnosis ($52,899). Hospitalizations with CCHDs accounted for 26.7% of all costs for CHD hospitalizations, with hypoplastic left heart syndrome, coarctation of the aorta, and tetralogy of Fallot having the highest total costs., Conclusion: Hospitalizations for children with CHDs have disproportionately high hospital costs compared with other pediatric hospitalizations, and the 17% of hospitalizations with CCHD diagnoses accounted for 27% of CHD hospital costs., (© 2014 Wiley Periodicals, Inc.)

Background: Loss of fertility has been reported as an important concern of reproductive age women diagnosed with cancer. The Furthering Understanding of Cancer, Health, and Survivorship In Adult (FUCHSIA) Women's Study examines how cancer treatment affects the fertility of cancer survivors who were diagnosed during their reproductive years. In this paper we discuss the process of developing and pilot testing the FUCHSIA computer assisted telephone interview (CATI)., Methods: The CATI was developed in several phases and pilot tested twice to evaluate several aspects of the instrument including question sequencing, understandability of the questions, and women's comfort with certain questions. Participants were recruited from cancer and infertility support groups and study team contacts., Results: Fifty-two women were recruited and participated in the first pilot. The participants had a mean age of 31.5 years, 17.3% had cancer, and 38.5% experienced a period of infertility. Twenty-four women participated in the second pilot with similar representation., Conclusions: The collection of detailed information on reproductive outcomes with the CATI may improve the understanding of how cancer treatment during the reproductive years affects female fertility. The pilot studies provided important information to improve the CATI before the full study. Our comprehensive recruitment strategy allowed us to interview a diverse group of women to ensure that questions and answer choices were easily interpreted, check complicated skip patterns and the flow of questions, and evaluate the length of the interview. This experience can be used to help inform others in what steps can be useful for developing telephone interviews for research studies.

Background: Congenital hydrocephalus is a condition characterized by accumulation of cerebrospinal fluid in the ventricles of the brain. Prenatal infections are risk factors for some birth defects. This pilot study investigated whether residual dried blood spots (DBS) could be used to assess infections as risk factors for birth defects by examining the associations between prenatal infection with Toxoplasma gondii (T. gondii) or cytomegalovirus (CMV) with congenital hydrocephalus., Methods: Case-infants with hydrocephalus (N=410) were identified among live-born infants using birth defects surveillance systems in California, North Carolina, and Texas. Control-infants without birth defects were randomly selected from the same geographic areas and time periods as case-infants (N=448). We tested residual DBS from case- and control-infants for T. gondii immunoglobulin M and CMV DNA. When possible, we calculated crude odds ratios (cORs) and confidence intervals (CIs)., Results: Evidence for prenatal T. gondii infection was more common among case-infants (1.2%) than control-infants (0%; p=0.11), and evidence for prenatal CMV infection was higher among case-infants (1.5%) than control-infants (0.7%; cOR: 2.3; 95% CI: 0.48, 13.99)., Conclusions: Prenatal infections with T. gondii and CMV occurred more often among infants with congenital hydrocephalus than control-infants, although differences were not statistically significant. This pilot study highlighted some challenges in using DBS to examine associations between certain infections and birth defects, particularly related to reduced sensitivity and specimen storage conditions. Further study with increased numbers of specimens and higher quality specimens should be considered to understand better the contribution of these infections to the occurrence of congenital hydrocephalus., (Copyright © 2013 Wiley Periodicals, Inc.)