Implementation of a Shared Data Repository and Common Data Dictionary for Fetal Alcohol Spectrum Disorders Research

Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed due to both structural differences in the collected data as well as difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data. Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly amongst different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth. We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data which conform to the data dictionaries reach the CI-FASD Central Repository. The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, collected using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository

Asthma control in pregnancy and selected drug therapy in relation to perinatal outcomes

Background: Asthma is a serious chronic condition which affects up to 8% of pregnant women in the United States. While severe or poorly controlled asthma might significantly complicate pregnancy and harm both mother and fetus, adequate asthma therapy in pregnancy is challenging to accomplish due to safety concerns for the fetus. Objective: This dissertation aimed to evaluate: 1) the effect of maternal asthma control on adverse perinatal outcomes; 2) the effect of fetal sex on maternal asthma control in pregnancy; and 3) the safety of asthma controller mediations, leukotriene receptor antagonists (LTRA), in pregnancy. Methods: Subjects were participants of the Organization of Teratology Information Specialists Asthma Medications in Pregnancy Study. Information about maternal medication use, asthma control, demographic and lifestyle characteristics, pregnancy complications, and perinatal outcomes was prospectively collected from 1,165 pregnant women. Results: The incidence of preterm delivery was significantly higher among women with inadequate asthma symptom control (OR=1.93; 95% CI: 1.10; 3.40) and women requiring hospitalization(s) for asthma exacerbations during pregnancy (OR=2.29; 95% CI: 1.06; 4.94) independent of other risk factors. Asthmatic pregnant women carrying a girl had more hospitalizations for asthma during pregnancy and a tendency of having more unscheduled asthma clinic visits compared with women carrying a boy. Fetal sex did not influence the association between maternal asthma control and fetal growth. The birth prevalence of major structural anomalies in children born to LTRA users was significantly higher compared with non-asthmatic controls (p=0.007), but not different from the asthmatic comparison group (p=0.524). Furthermore, the birth defects in the LTRA group did not represent a consistent pattern. Use of LTRAs was not associated with large risks of other adverse perinatal outcomes. Conclusions: This study demonstrates a substantial risk posed by poorly controlled maternal asthma on preterm delivery. Pregnant asthmatic women carrying a girl might be more susceptible to asthma exacerbations, particularly early in pregnancy; however, all women with asthma should be carefully monitored for pregnancy-associated changes in asthma symptoms. LTRAs do not appear to be a major human teratogen; however, results should be interpreted with caution due to the relatively small number of women taking LTRA

Forty Years of Assessing Neurodevelopmental and Behavioral Effects of Prenatal Alcohol Exposure in Infants: What Have We Learned?

It has been known for over 4 decades that prenatal alcohol exposure (PAE) can adversely affect neurodevelopment and behavior (NDB). Yet, early detection of altered NDB due to PAE continues to present a major clinical challenge. Identification of altered NDB in the first 2 years of life, before higher-order cognitive processes develop, invites early interventions for affected children to improve long-term outcomes. Studies published in English from January of 1980 to July of 2018 were identified in PubMed/MEDLINE. The review focused on prospective birth cohort studies which used standardized NDB assessments in children up to 2 years of age, wherein PAE was the main exposure and NDB was the main outcome. NDB was categorized into the domains of neurocognitive, adaptive, and self-regulation based on the 2016 Updated Clinical Guidelines for Diagnosing fetal alcohol spectrum disorder. An initial search resulted in 1,867 articles for which we reviewed abstracts; 114 were selected for full-text review; and 3 additional abstracts were identified through review of references in eligible publications. Thirty-one publications met criteria and were included: of these, 24 reported neurocognitive outcomes, 24 reported adaptive behavior outcomes, and 12 reported outcomes in the domain of self-regulation. Although self-regulation was assessed in the fewest number of studies, 8/12 (75%) reported PAE-associated deficits. In contrast, results were mixed for the other 2 domains: 13/24 (54%) of the selected studies that included neurocognitive outcomes showed poorer performance following PAE, and 8/24 (33%) studies that assessed adaptive functioning found significant differences between PAE and comparison infants. There is considerable evidence to support the value of early-life assessments of infant NDB when PAE is known or suspected. More studies focusing on infant self-regulation, in particular, are needed to determine the utility of early evaluation of this critical developmental domain in infants with PAE

The effect of prenatal substance use and maternal contingent responsiveness on infant affect.

BACKGROUND: The effects of prenatal substance exposure on neurobehavioral outcomes are inherently confounded by the effects of the postnatal environment, making it difficult to disentangle their influence. The goal of this study was to examine the contributing effects of prenatal substance use and parenting style (operationalized as contingent responding during the play episodes of the Still-face paradigm [SFP]) on infant affect. METHODS: A prospective cohort design was utilized with repeated assessment of substance use during pregnancy and the administration of the SFP, which measures infant response to a social stressor, at approximately 6months of age. Subjects included 91 dyads classified into four groups: 1) Control (n=34); 2) Medication assisted therapy for opioid dependence (MAT; n=19); 3) Alcohol (n=15); 4) Alcohol+MAT (n=23). Mean % of positive infant affect and mean % of maternal responsiveness (watching, attention seeking, and contingent responding) was compared among the five SFP episodes across the four study groups by MANOVA. Mixed effects modelling was used to estimate the contributing effects of the study groups and maternal responsiveness on infant affect. RESULTS: Maternal contingent responding was associated with increase (β̂=0.84; p CONCLUSIONS: Higher maternal responsiveness was a much stronger predictor of infant behavior than prenatal exposures, providing the basis for future intervention studies focusing on specific parenting strategies

Barriers and facilitators to dispensing of intranasal naloxone by pharmacists.

BACKGROUND: Although misuse of prescription opioids has reached epidemic proportions, pharmacy-based preventive services to combat this epidemic are limited. The aims of this study were to identify barriers and facilitators to the dispensing of intranasal naloxone (INN) by pharmacists in New Mexico. METHODS: For this mixed-methods study, a qualitative component (focus group) informed the development of a quantitative component (electronic survey) distributed to all pharmacists registered with the New Mexico Board of Pharmacy and practicing in the state. A 46-item survey included questions about pharmacists\u27 concerns regarding dispensing INN, barriers and facilitators to dispensing INN, efforts needed to increase availability and utilization of pharmacist-dispensed INN, and characteristics of respondents and their pharmacies. RESULTS: Pharmacists from all geographical regions and all types of pharmacy settings were represented in the sample (final N = 390, participation rate 23.5%, including a subset of 182 community pharmacists). The main barriers identified were (1) out-of-pocket costs for patients; (2) time constraints for pharmacists; and (3) inadequate reimbursement for pharmacists. The main facilitators were (1) increased awareness among opioid-using patients and family members about the need for INN; (2) additional education to the general public; and (3) additional training for pharmacists on how to initiate discussions about INN with high-risk patients. Some community pharmacists were concerned that INN dispensing would promote opioid abuse (16.5%) and attract undesirable clientele (14.3%). In a multivariable logistic regression analysis of a community pharmacy subset, a higher number of concerns about INN (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.82-0.93) and a pharmacy setting in a chain grocery or a big box store (OR = 0.38; 95% CI: 0.16-0.92) were associated with decreased odds of dispensing INN. CONCLUSIONS: Effective intervention strategies for increasing dispensing of intranasal naloxone by pharmacists should focus on pharmacists\u27 concerns, include education to multiple audiences, and address provider-level, system-level, and society-level barriers

Dietary Intake Among Opioid- and Alcohol-Using Pregnant Women.

BACKGROUND: Substance abuse in nonpregnant adults has been associated with increased intake in calories and decreased intake of nutrient-dense foods; however, studies examining dietary intake in opioid-using and alcohol-using pregnant women are lacking. OBJECTIVE: The objective of this study was to evaluate dietary intake in opioid-using pregnant women with or without concurrent light-to-moderate alcohol use as compared to abstaining controls. METHODS: This prospective birth cohort included 102 pregnant women classified into four study groups: controls (n = 27), medication-assisted treatment (MAT; n = 26), alcohol (ALC; n = 22), and concurrent use of both substances (MAT + ALC; n = 27). Percentage differences in macro- and micronutrient intake were estimated from the food frequency questionnaire and compared among the study groups. Proportions of participants with intakes below the estimated average requirements (EAR) based on diet and diet with supplements were estimated. RESULTS: Three exposed groups had lower prevalence of multivitamin use in periconceptional period (11.5-31.8%) than controls (44.4%). Unadjusted mean energy intake was significantly higher in the MAT + ALC group compared to controls, while micronutrient intake per 1000 kcal was the highest in the control group for almost all of the micronutrients analyzed. After adjustment for energy intake and sociodemographic characteristics, MAT group had lower estimated dietary intake of iron (-15.0%, p = 0.04) and folate (-16.8%, p = 0.04) compared to controls. A high proportion of participants in all study groups had dietary intake below the EAR for vitamin E, iron, and folate. CONCLUSION: Results highlight the need for targeted dietary interventions for opioid-using pregnant women