Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

2023

1772-1779

05/2023

1530-0447

BACKGROUND: While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood.

METHODS: This paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period.

RESULTS: Primary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social-emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment.

CONCLUSIONS: The OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development.

IMPACT: This study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker. Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development. While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

10.1038/s41390-022-02279-2

Pediatr Res

36042329

Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

2023

1772-1779

05/2023

1530-0447

BACKGROUND: While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood.

METHODS: This paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period.

RESULTS: Primary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social-emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment.

CONCLUSIONS: The OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development.

IMPACT: This study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker. Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development. While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

10.1038/s41390-022-02279-2

Pediatr Res

36042329

Psychometric Properties of the Prenatal Opioid Use Perceived Stigma Scale and Its Use in Prenatal Care.

2023

150-158

03/2023

1552-6909

OBJECTIVE: To examine the psychometric properties of the Prenatal Opioid Use Perceived Stigma (POPS) scale and to assess the relationship of POPS scores to adequate prenatal care.

DESIGN: Prospective cohort study.

SETTING: Medical centers in Alabama, Ohio, and Pennsylvania (N = 4).

PARTICIPANTS: Women (N = 127) who took opioids during pregnancy and whose infants participated in the Outcomes of Babies With Opioid Exposure Study.

METHODS: Participants reported their perceptions of stigma during pregnancy by responding to the eight items on the POPS scale. We evaluated the instrument's internal consistency reliability (Cronbach's alpha), structural validity (factor analysis), and convergent validity (relationship with measures of similar constructs). In addition, to assess construct validity, we used logistic regression to examine the relationship of POPS scores to the receipt of adequate prenatal care.

RESULTS: The internal consistency of the POPS scale was high (Cronbach's α = .88), and all item-total correlations were greater than 0.50. The factor analysis confirmed that the items cluster into one factor. Participants who reported greater perceived stigma toward substance users and everyday discrimination in medical settings had higher POPS scores, which supported the convergent validity of the scale. POPS scores were significantly associated with not receiving adequate prenatal care, adjusted OR = 1.47, 95% confidence interval [1.19, 1.83], p < .001.

CONCLUSION: The psychometric testing of the POPS scale provided initial support for the reliability and validity of the instrument. It may be a useful tool with which to assess perceived stigma among women who take opioids, a potential barrier to seeking health care during pregnancy.

10.1016/j.jogn.2022.12.002

J Obstet Gynecol Neonatal Nurs

36696952

Psychometric Properties of the Prenatal Opioid Use Perceived Stigma Scale and Its Use in Prenatal Care.

2023

01/2023

1552-6909

OBJECTIVE: To examine the psychometric properties of the Prenatal Opioid Use Perceived Stigma (POPS) scale and to assess the relationship of POPS scores to adequate prenatal care.

DESIGN: Prospective cohort study.

SETTING: Medical centers in Alabama, Ohio, and Pennsylvania (N = 4).

PARTICIPANTS: Women (N = 127) who took opioids during pregnancy and whose infants participated in the Outcomes of Babies With Opioid Exposure Study.

METHODS: Participants reported their perceptions of stigma during pregnancy by responding to the eight items on the POPS scale. We evaluated the instrument's internal consistency reliability (Cronbach's alpha), structural validity (factor analysis), and convergent validity (relationship with measures of similar constructs). In addition, to assess construct validity, we used logistic regression to examine the relationship of POPS scores to the receipt of adequate prenatal care.

RESULTS: The internal consistency of the POPS scale was high (Cronbach's α = .88), and all item-total correlations were greater than 0.50. The factor analysis confirmed that the items cluster into one factor. Participants who reported greater perceived stigma toward substance users and everyday discrimination in medical settings had higher POPS scores, which supported the convergent validity of the scale. POPS scores were significantly associated with not receiving adequate prenatal care, adjusted OR = 1.47, 95% confidence interval [1.19, 1.83], p < .001.

CONCLUSION: The psychometric testing of the POPS scale provided initial support for the reliability and validity of the instrument. It may be a useful tool with which to assess perceived stigma among women who take opioids, a potential barrier to seeking health care during pregnancy.

10.1016/j.jogn.2022.12.002

J Obstet Gynecol Neonatal Nurs

36696952

Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

2022

08/2022

1530-0447

BACKGROUND: While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood.

METHODS: This paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period.

RESULTS: Primary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social-emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment.

CONCLUSIONS: The OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development.

IMPACT: This study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker. Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development. While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

10.1038/s41390-022-02279-2

Pediatr Res

36042329

Promoting Human Milk and Breastfeeding for the Very Low Birth Weight Infant.

2021

2021 Oct 11

1098-4275

<p>Provision of mother's own milk for hospitalized very low birth weight (VLBW) (≤1500 g) infants in the NICU provides short- and long-term health benefits. Mother's own milk, appropriately fortified, is the optimal nutrition source for VLBW infants. Every mother should receive information about the critical importance of mother's own milk to the health of a VLBW infant. Pasteurized human donor milk is recommended when mother's own milk is not available or sufficient. Neonatal health care providers can support lactation in the NICU and potentially reduce disparities in the provision of mother's own milk by providing institutional supports for early and frequent milk expression and by promoting skin-to-skin contact and direct breastfeeding, when appropriate. Promotion of human milk and breastfeeding for VLBW infants requires multidisciplinary and system-wide adoption of lactation support practices.</p>

10.1542/peds.2021-054272

Pediatrics

34635582

Use of Probiotics in Preterm Infants.

2021

2021 May 24

1098-4275

<p>Probiotic products in the United States are available for use in the general category of dietary supplements, bypassing the rigor of the US Food and Drug Administration (FDA) approval process in safety, efficacy, and manufacturing standards. As a result, currently available probiotics lack FDA-approved drug labeling and cannot be marketed to treat or prevent disease in preterm infants, including necrotizing enterocolitis and late-onset sepsis. Despite lack of availability of a pharmaceutical-grade product, the number of preterm infants receiving probiotics in the United States and Canada is steadily increasing. According to recent reports from large collaborative databases in the United States, approximately 10% of extremely low gestational age neonates receive a probiotic preparation during their stay in the NICU, with wide variation in practice among units. In sum, more than 10 000 preterm infants have been enrolled in randomized clinical trials of probiotic supplementation worldwide. Methodologic differences among study protocols included different strains and combinations of therapy, masking of trials, and a priori definitions of the primary outcome measure. Large meta-analyses of these trials have demonstrated the efficacy of multiple-strain probiotics in reducing necrotizing enterocolitis and all-cause mortality, whereas the efficacy of single-strain probiotic preparations is less certain. In the absence of an appropriate medical-grade product in the United States, dietary supplement-grade probiotics, some of which have been the subject of recent recalls for contamination, are being prescribed. Given the lack of FDA-regulated pharmaceutical-grade products in the United States, conflicting data on safety and efficacy, and potential for harm in a highly vulnerable population, current evidence does not support the routine, universal administration of probiotics to preterm infants, particularly those with a birth weight of &lt;1000 g.</p>

10.1542/peds.2021-051485

Pediatrics

34031231

Neonatal Opioid Withdrawal Syndrome.

2020

2020 Oct 26

1098-4275

<p>The opioid crisis has grown to affect pregnant women and infants across the United States, as evidenced by rising rates of opioid use disorder among pregnant women and neonatal opioid withdrawal syndrome among infants. Across the country, pregnant women lack access to evidence-based therapies, including medications for opioid use disorder, and infants with opioid exposure frequently receive variable care. In addition, public systems, such as child welfare and early intervention, are increasingly stretched by increasing numbers of children affected by the crisis. Systematic, enduring, coordinated, and holistic approaches are needed to improve care for the mother-infant dyad. In this statement, we provide an overview of the effect of the opioid crisis on the mother-infant dyad and provide recommendations for management of the infant with opioid exposure, including clinical presentation, assessment, treatment, and discharge.</p>

10.1542/peds.2020-029074

Pediatrics

33106341

Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies.

2020

e200593

2020 May 04

2168-6211

<p><strong>Importance: </strong>Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies.</p>

<p><strong>Objective: </strong>To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants.</p>

<p><strong>Design, Setting, and Participants: </strong>This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020.</p>

<p><strong>Main Outcomes and Measures: </strong>Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death.</p>

<p><strong>Results: </strong>A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008).</p>

<p><strong>Conclusions and Relevance: </strong>In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.</p>

10.1001/jamapediatrics.2020.0593

JAMA Pediatr

32364598

The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants: An Evidence-Based Approach.

2019

2019 Apr 17

1535-4970

<p><strong>RATIONALE: </strong>Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, nor adequately predict childhood morbidity.</p>

<p><strong>OBJECTIVE: </strong>To determine which of 18 pre-specified, revised definitions of bronchopulmonary dysplasia, that variably define disease presence and severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks postmenstrual age, best predicts death or serious respiratory morbidity through 18-26 months corrected age.</p>

<p><strong>METHODS: </strong>We assessed infants born &lt;32 weeks' gestation between 2011-2015 at 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network.</p>

<p><strong>RESULTS: </strong>Of 2677 infants, 683 (26%) died or developed serious respiratory morbidity. The criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks postmenstrual age, irrespective of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support (n=773); grade 1, nasal cannula ≤2L/min (n=1038); grade 2, nasal cannula &gt;2L/min or non-invasive positive airway pressure (n=617); and grade 3, invasive mechanical ventilation (n=249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33%-79%) was observed for death or neurodevelopmental impairment.</p>

<p><strong>CONCLUSIONS: </strong>The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support at 36 weeks postmenstrual age, irrespective of supplemental oxygen use. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial License 4.0 (http://creativecommons.org/licenses/by-nc/4.0/).</p>

10.1164/rccm.201812-2348OC

Am. J. Respir. Crit. Care Med.

30995069