Changes in Provider Perceptions and Practices Regarding Dosing Units for Oral Liquid Medications.

OBJECTIVE: A 2015 survey of primary care providers (PCPs) found that while many believed that milliliter (mL)-only dosing was safest for oral liquid medications, few would use mL alone in dosing instructions. Since 2015, many recommendations have promoted "mL-only" dosing. In 2019, a follow-up survey was conducted to assess if PCP perceptions and practices have changed. METHODS: Pediatricians, family medicine physicians, nurse practitioners, and internists participating in the 2015 and 2019 DocStyles cross-sectional, web-based surveys were asked about their perceptions and practices regarding dosing units for oral liquid medications. RESULTS: In 2019, among 1392 respondents, the proportion of PCPs who reported they believed using mL-only is the safest dosing instruction ranged from 55.1% of internists to 80.8% of pediatricians. While fewer PCPs believed patients/caregivers prefer dosing instructions in mL-only (23.9% of nurse practitioners to 48.4% of pediatricians), more held this belief in 2019 compared to 2015; pediatricians had the greatest absolute increase (+14.4%) and family medicine physicians had the smallest increase (+1.3%). While 61.6% of pediatricians reported they would use mL-only dosing, only 36.0% of internists, 36.6% of nurse practitioners, and 42.5% of family medicine physicians reported they would do so. After controlling for age, gender, region, and specialty, 2019 PCP survey participants were more likely to report that they would use mL-only dosing compared to 2015 participants (adjusted odds ratio 1.51, 95% confidence interval 1.29-1.77). CONCLUSIONS: Broader educational efforts may be necessary to reach nonpediatricians, to encourage prescribing and communication with patients/caregivers using mL-only dosing.

Trends in Emergency Department Visits for Unsupervised Pediatric Medication Exposures.

INTRODUCTION: Emergency department visits and hospitalizations for unsupervised medication exposures among young children increased in the early 2000s. Prevention efforts were initiated in response. METHODS: Nationally representative data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project collected from 2009 to 2020 were analyzed in 2022 to assess overall and medication-specific trends in emergency department visits for unsupervised exposures among children aged ≤5 years. RESULTS: From 2009 to 2020, there were an estimated 677,968 (95% CI=550,089, 805,846) emergency department visits for unsupervised medication exposures among children aged ≤5 years in the U.S. Most visits involved children aged 1-2 years (2009-2012 [70.3%], 2017-2020 [67.4%]), and nearly one half involved prescription solid medications (2009-2012 [49.4%], 2017-2020 [48.1%]). The largest declines in estimated numbers of annual visits from 2009-2012 to 2017-2020 were for exposures involving prescription solid benzodiazepines (-2,636 visits, -72.0%) and opioids (-2,596 visits, -53.6%) and over-the-counter liquid cough and cold medications (-1,954 visits, -71.6%) and acetaminophen (-1,418 visits, -53.4%). The estimated number of annual visits increased for exposures involving over-the-counter solid herbal/alternative remedies (+1,028 visits, +65.6%), with the largest increase for melatonin exposures (+1,440 visits, +421.1%). Overall, the estimated number of visits for unsupervised medication exposures decreased from 66,416 in 2009 to 36,564 in 2020 (annual percentage change= -6.0%). Emergent hospitalizations for unsupervised exposures also declined (annual percentage change= -4.5%). CONCLUSIONS: Declines in estimated emergency department visits and hospitalizations for unsupervised medication exposures from 2009 to 2020 coincided with renewed prevention efforts. Targeted approaches may be needed to achieve continued declines in unsupervised medication exposures among young children.

Trends in Prescribing of Antibiotics and Drugs Investigated for Coronavirus Disease 2019 (COVID-19) Treatment in US Nursing Home Residents During the COVID-19 Pandemic.

BACKGROUND: Trends in prescribing for nursing home (NH) residents, which may have been influenced by the coronavirus disease 2019 (COVID-19) pandemic, have not been characterized. METHODS: Long-term care pharmacy data from 1944 US NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1000 residents serviced was calculated from January to October and compared as relative percent change from 2019 to 2020. RESULTS: In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval [CI]: 5.87, 7.48) and azithromycin (+150%, 95% CI: 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI: 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI: .55, .73) and 303% higher in July (95% CI: 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (-5%, 95% CI: .94, .97) through October (-4%, 95% CI: .94, .97) in 2020 compared to 2019. CONCLUSIONS: During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety.

US emergency department visits for acute harms from over-the-counter cough and cold medications, 2017-2019.

BACKGROUND AND PURPOSE: Characterization of emergency department (ED) visits for acute harms related to use of over-the-counter cough and cold medications (CCMs) by patient demographics, intent of CCM use, concurrent substance use, and clinical manifestations can help guide prevention of medication harms. METHODS: Public health surveillance data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were used to estimate numbers and population rates of ED visits from 2017 to 2019. RESULTS: Based on 1396 surveillance cases, there were an estimated 26 735 (95% CI, 21 679-31 791) US ED visits for CCM-related harms annually, accounting for 1.3% (95% CI, 1.2-1.5%) of all ED visits for medication adverse events. Three fifths (61.4%, 95% CI, 55.6-67.2%) of these visits were attributed to non-therapeutic CCM use (nonmedical use, self-harm, unsupervised pediatric exposures). Most visits by children aged <4 years (74.0%, 95% CI, 59.7-88.3%) were for unsupervised CCM exposures. Proportion hospitalized was higher for visits for self-harm (76.5%, 95% CI, 68.9-84.2%) than for visits for nonmedical use (30.3%, 95% CI, 21.1-39.6%) and therapeutic use (8.8%, 95% CI, 5.9-11.8%). Overall, estimated population rates of ED visits for CCM-related harms were higher for patients aged 12-34 years (16.5 per 100 000, 95% CI, 13.0-20.0) compared with patients aged <12 years (5.1 per 100 000, 95% CI, 3.6-6.5) and ≥ 35 years (4.3 per 100 000, 95% CI, 3.4-5.1). Concurrent use of other medications, illicit drugs, or alcohol was frequent in ED visits for nonmedical use (61.3%) and self-harm (75.9%). CONCLUSIONS: Continued national surveillance of CCM-related harms can assess progress toward safer use.

US Emergency Department Visits Attributed to Medication Harms, 2017-2019.

IMPORTANCE: Assessing the scope of acute medication harms to patients should include both therapeutic and nontherapeutic medication use. OBJECTIVE: To describe the characteristics of emergency department (ED) visits for acute harms from both therapeutic and nontherapeutic medication use in the US. DESIGN, SETTING, AND PARTICIPANTS: Active, nationally representative, public health surveillance based on patient visits to 60 EDs in the US participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project from 2017 through 2019. EXPOSURES: Medications implicated in ED visits, with visits attributed to medication harms (adverse events) based on the clinicians' diagnoses and supporting data documented in the medical record. MAIN OUTCOMES AND MEASURES: Nationally weighted estimates of ED visits and subsequent hospitalizations for medication harms. RESULTS: Based on 96 925 cases (mean patient age, 49 years; 55% female), there were an estimated 6.1 (95% CI, 4.8-7.5) ED visits for medication harms per 1000 population annually and 38.6% (95% CI, 35.2%-41.9%) resulted in hospitalization. Population rates of ED visits for medication harms were higher for patients aged 65 years or older than for those younger than 65 years (12.1 vs 5.0 [95% CI, 7.4-16.8 vs 4.1-5.8] per 1000 population). Overall, an estimated 69.1% (95% CI, 63.6%-74.7%) of ED visits for medication harms involved therapeutic medication use, but among patients younger than 45 years, an estimated 52.5% (95% CI, 48.1%-56.8%) of visits for medication harms involved nontherapeutic use. The proportions of ED visits for medication harms involving therapeutic use were lowest for barbiturates (6.3%), benzodiazepines (11.1%), nonopioid analgesics (15.7%), and antihistamines (21.8%). By age group, the most frequent medication types and intents of use associated with ED visits for medication harms were therapeutic use of anticoagulants (4.5 [95% CI, 2.3-6.7] per 1000 population) and diabetes agents (1.8 [95% CI, 1.3-2.3] per 1000 population) for patients aged 65 years and older; therapeutic use of diabetes agents (0.8 [95% CI, 0.5-1.0] per 1000 population) for patients aged 45 to 64 years; nontherapeutic use of benzodiazepines (1.0 [95% CI, 0.7-1.3] per 1000 population) for patients aged 25 to 44 years; and unsupervised medication exposures (2.2 [95% CI, 1.8-2.7] per 1000 population) and therapeutic use of antibiotics (1.4 [95% CI, 1.0-1.8] per 1000 population) for children younger than 5 years. CONCLUSIONS AND RELEVANCE: According to data from 60 nationally representative US emergency departments, visits attributed to medication harms in 2017-2019 were frequent, with variation in products and intent of use by age.

Opioid prescription claims among women aged 15-44 years-United States, 2013-2017.

OBJECTIVE: To estimate the annual percentage of women of reproductive age with private insurance or Medicaid who had opioid prescription claims during 2013-2017 and describe trends over time. DESIGN: A secondary analysis of insurance claims data from IBM MarketScan® Commercial and Multi-State Medicaid Databases to assess outpatient pharmacy claims for prescription opioids among women aged 15-44 years during 2013-2017. PARTICIPANTS: Annual cohorts of 3.5-3.8 million women aged 15-44 years with private insurance and 0.9-2.1 million women enrolled in Medicaid. MAIN OUTCOME MEASURE: The percentage of women aged 15-44 years with outpatient pharmacy claims for opioid prescriptions. RESULTS: During 2013-2017, the proportion of women aged 15-44 years with private insurance who had claims for opioid prescriptions decreased by 22.1 percent, and among women enrolled in Medicaid, the proportion decreased by 31.5 -percent. CONCLUSIONS: Opioid prescription claims decreased from 2013 to 2017 among insured women of reproductive age. However, opioid prescription claims remained common and were more common among women enrolled in Medicaid than those with private insurance; additional strategies to improve awareness of the risks associated with opioid prescribing may be needed.

Trends in US Outpatient Antibiotic Prescriptions During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: The objective of our study was to describe trends in US outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). METHODS: We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies from January 2017 through May 2020. We averaged estimates from 2017 through 2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017-2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. RESULTS: From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. CONCLUSIONS: From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected because of seasonal trends alone, possibly related to the coronavirus disease 2019 pandemic and associated mitigation measures.

Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects.

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.

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

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

Emergency Department Visits Attributed to Adverse Events Involving Benzodiazepines, 2016-2017.

INTRODUCTION: Characterization of emergency department visits attributed to adverse events involving benzodiazepines can be used to guide preventive interventions. This study describes U.S. emergency department visits attributed to adverse events involving benzodiazepines by intent, patient characteristics, and clinical manifestations. METHODS: Data from the 2016-2017 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2019 to calculate estimated annual numbers and rates of emergency department visits attributed to adverse events involving benzodiazepines, by intent of benzodiazepine use. RESULTS: Based on 6,148 cases, there were an estimated 212,770 (95% CI=167,163, 258,377) emergency department visits annually attributed to adverse events involving benzodiazepines. More than half were visits involving nonmedical use of benzodiazepines (119,008; 55.9%, 95% CI=50.0%, 61.9%), one third were visits involving self-harm with benzodiazepines (64,721; 30.4%, 95% CI=25.6%, 35.2%), and a smaller proportion of visits involved therapeutic use of benzodiazepines (29,041; 13.6%, 95% CI=11.4%, 15.9%). The estimated population rate of visits was highest for nonmedical use of benzodiazepines by patients aged 15-34 years (7.4 visits per 10,000 people). Among visits involving nonmedical use of benzodiazepines, 54.8% (95% CI=49.8%, 59.8%) were made by patients aged 15-34 years, 82.7% (95% CI=80.1%, 85.4%) involved concurrent use of other substances (illicit drugs, alcohol, prescription opioids, and/or other pharmaceuticals), and 24.2% (95% CI=17.7%, 30.6%) involved cardiorespiratory arrest or unresponsiveness. CONCLUSIONS: These findings support recommendations to assess for and address substance use disorder before initiating or continuing benzodiazepines and reinforce the need for validated self-harm risk assessment tools for clinicians.

ADHD Medication Use During Pregnancy and Risk for Selected Birth Defects: National Birth Defects Prevention Study, 1998-2011.

Objective: The objective of this study was to examine the prevalence of, and maternal characteristics associated with, ADHD medication use before and during pregnancy, and associations between early pregnancy ADHD medication use and risk for 12 selected birth defects. Method: We used data from the National Birth Defects Prevention Study (1998-2011), a U.S. population-based case-control study examining risk factors for major structural birth defects. Results: There was an increase in ADHD medication use from 1998-1999 (0.2%) to 2010-2011 (0.5%; p < .001). Early pregnancy ADHD medication use was more commonly reported by mothers of infants/fetuses with gastroschisis (crude odds ratio [cOR]: 2.9, 95% confidence interval [CI] = [1.2, 6.9]), omphalocele (cOR: 4.0, 95% CI = [1.2, 13.6]), and transverse limb deficiency (cOR: 3.3, 95% CI = [1.1, 9.6]). Conclusion: ADHD medication use before and during pregnancy was rare, but the prevalence of use has increased over time. In this analysis, early pregnancy ADHD medication use was associated with three of 12 selected birth defects.

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

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

Atypical antipsychotic use during pregnancy and birth defect risk: National Birth Defects Prevention Study, 1997-2011.

PURPOSE: To examine the prevalence of, and factors associated with, atypical antipsychotic use among U.S. pregnant women, and potential associations between early pregnancy atypical antipsychotic use and risk for 14 birth defects. METHODS: We analyzed data from the National Birth Defects Prevention Study (1997-2011), a U.S. population-based case-control study examining risk factors for major structural birth defects. RESULTS: Atypical antipsychotic use during pregnancy was more common among women with pre-pregnancy obesity, and women who reported illicit drug use before and during pregnancy, smoking during pregnancy, alcohol use during pregnancy, or use of other psychiatric medications during pregnancy. We observed elevated associations (defined as a crude odds ratio [cOR] ≥2.0) between early pregnancy atypical antipsychotic use and conotruncal heart defects (6 exposed cases; cOR: 2.3, 95% confidence interval [CI]: 0.9-6.1), and more specifically Tetralogy of Fallot (3 exposed cases; cOR: 2.5, 95% CI: 0.7-8.8), cleft palate (4 exposed cases, cOR: 2.5, 95% CI: 0.8-7.6), anorectal atresia/stenosis (3 exposed cases, cOR: 2.8, 95% CI: 0.8-9.9), and gastroschisis (3 exposed cases, cOR: 2.1, 95% CI: 0.6-7.3). CONCLUSIONS: Our findings support the close clinical monitoring of pregnant women using atypical antipsychotics. Women treated with atypical antipsychotics generally access healthcare services before pregnancy; efforts to reduce correlates of atypical antipsychotic use might improve maternal and infant health in this population.

Leveraging Existing Birth Defects Surveillance Infrastructure to Build Neonatal Abstinence Syndrome Surveillance Systems - Illinois, New Mexico, and Vermont, 2015-2016.

Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome that can occur following prenatal exposure to opioids (1). NAS surveillance in the United States is based largely on diagnosis codes in hospital discharge data, without validation of these codes or case confirmation. During 2004-2014, reported NAS incidence increased from 1.5 to 8.0 per 1,000 U.S. hospital births (2), based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes identified in hospital discharge data, without case confirmation. However, little is known about how well these codes identify NAS or how the October 1, 2015, transition from ICD-9-CM to the tenth revision of ICD-CM (ICD-10-CM) codes affected estimated NAS incidence. This report describes a pilot project in Illinois, New Mexico, and Vermont to use birth defects surveillance infrastructure to obtain state-level, population-based estimates of NAS incidence among births in 2015 (all three states) and 2016 (Illinois) using hospital discharge records and other sources (varied by state) with case confirmation, and to evaluate the validity of NAS diagnosis codes used by each state. Wide variation in NAS incidence was observed across the three states. In 2015, NAS incidence for Illinois, New Mexico, and Vermont was 3.0, 7.5, and 30.8 per 1,000 births, respectively. Among evaluated diagnosis codes, those with the highest positive predictive values (PPVs) for identifying confirmed cases of NAS, based on a uniform case definition, were drug withdrawal syndrome in a newborn (ICD-9-CM code 779.5; state range = 58.6%-80.2%) and drug withdrawal, infant of dependent mother (ICD-10-CM code P96.1; state range = 58.5%-80.2%). The methods used to assess NAS incidence in this pilot project might help inform other states' NAS surveillance efforts.

Evaluation of State-Mandated Reporting of Neonatal Abstinence Syndrome - Six States, 2013-2017.

From 2004 to 2014, the incidence of neonatal abstinence syndrome (NAS) in the United States increased 433%, from 1.5 to 8.0 per 1,000 hospital births. The latest national data from 2014 indicate that one baby was born with signs of NAS every 15 minutes in the United States (1). NAS is a drug withdrawal syndrome that most commonly occurs among infants after in utero exposure to opioids, although other substances have also been associated with NAS. Prenatal opioid exposure has also been associated with poor fetal growth, preterm birth, stillbirth, and possible specific birth defects (2-5). NAS surveillance has often depended on hospital discharge data, which historically underestimate the incidence of NAS and are not available in real time, thus limiting states' ability to quickly direct public health resources (6,7). This evaluation focused on six states with state laws implementing required NAS case reporting for public health surveillance during 2013-2017 and reviews implementation of the laws, state officials' reports of data quality before and after laws were passed, and advantages and challenges of legally mandating NAS reporting for public health surveillance in the absence of a national case definition. Using standardized search terms in an online legal research database, laws in six states mandating reporting of NAS from medical facilities to state health departments (SHDs) or from SHDs to a state legislative body were identified. SHD officials in these six states completed a questionnaire followed by a semistructured telephone interview to clarify open-text responses from the questionnaire. Variability was found in the type and number of surveillance data elements reported and in how states used NAS surveillance data. Following implementation, five states with identified laws reported receiving NAS case reports within 30 days of diagnosis. Mandated NAS case reporting allowed SHDs to quantify the incidence of NAS in their states and to inform programs and services. This information might be useful to states considering implementing mandatory NAS surveillance.

Four years after implementation of a national micronutrient powder program in Kyrgyzstan, prevalence of iron deficiency and iron deficiency anemia is lower, but prevalence of vitamin A deficiency is higher.

BACKGROUND/OBJECTIVES: In 2009, the Ministry of Health of Kyrgyzstan launched a national Infant and Young Child Nutrition (IYCN) program which included point-of-use fortification of foods with micronutrient powders (MNP) containing iron, vitamin A, and other micronutrients. Caretakers of children aged 6-23 months were given 30 sachets of MNP every 2 months. Micronutrient surveys were conducted in 2009 and 2013. The objective of the study was to compare the prevalence of anemia and deficiencies of iron and vitamin A among children aged 6-29 months prior to the MNP program (2009) with those after full implementation (2013). SUBJECTS/METHODS: Cross-sectional national surveys were conducted in 2009 (n = 666) and 2013 (n = 2150). Capillary blood samples were collected to measure hemoglobin, iron (ferritin and soluble transferrin receptor [sTfR]) and vitamin A (retinol binding protein [RBP]) status, and inflammation status (C-reactive protein [CRP] and α-1-acid glycoprotein [AGP]). Ferritin, sTfR, and RBP were adjusted for inflammation; hemoglobin was adjusted for altitude. RESULTS: The prevalence of anemia was non-significantly lower in 2013 compared to 2009 (32.7% vs. 39.0%, p = 0.076). Prevalence of inflammation-adjusted iron deficiency (54.8% vs. 74.2%, p<0.001) and iron deficiency anemia (IDA, 25.5% vs. 35.1%, p = 0.003) were lower and the prevalence of inflammation-adjusted vitamin A deficiency was higher (4.3% vs. 2.0%, p = 0.013) in 2013 compared to 2009. CONCLUSIONS: Four years after the initiation of a national Infant and Young Child Nutrition program including the introduction of point-of-use fortification with MNP, the prevalence of iron deficiency and IDA is lower, but the prevalence of vitamin A deficiency is higher.