A search for guidance: examining prenatal substance exposure protocols.

Sudden unexplained infant death (SUID) is a devastating outcome for any family. In the United States, rates of SUID declined markedly from 1990 to 2000 because of public health messaging promoting supine sleep positioning.1 However, SUID rates have remained relatively unchanged between 2000 and 2020, with persistent racial and geographic disparities.1 A meta-analysis of literature through 2020 identified an association between increased risk of sudden infant death and prenatal substance exposure (PSE).2 Few studies, however, have been able to comprehensively investigate drivers of SUID among infants with PSE. In this issue of Pediatrics, Deutsch and colleagues’ investigation substantially adds to previous research by evaluating an array of factors known to be related to SUID, including bedsharing, supervisor impairment, social drivers of poor health, and family vulnerability among cases of sleep-related SUID among infants with and without PSE.3 Deutsch et al used the National Fatality Review-Case Reporting System, where local and state agencies completing infant mortality reviews submit data using a standardized reporting tool.4Deutsch and colleagues identified 2010 cases of sleep-related SUID reported between 2015 and 2020 and found that 14% of reported sleep-related SUID deaths had PSE.3 Among all cases, half of the deaths involved bedsharing with an adult, with no differences between infants with and without PSE. Additionally, 19% of cases were reported to have an impaired supervisor and 50% of supervisors were asleep at the time of infant death, with higher proportions among infants with PSE than unexposed infants.3 Notably, among cases with data available indicating supervisor impairment, the majority of cases also involved bedsharing, with no difference between infants with and without PSE.3The study is an important contribution to the relatively sparse literature around postnatal modifiable factors contributing to sleep-related SUID risk among infants, including those with PSE, yet also highlights the challenge of studying SUID (an extremely rare condition at a rate of 93 cases per 100 000 live births) and its risk factors.1 For example, without inclusion of a non-SUID control group, caution is needed when interpreting the significance of the risk factors identified among infants with PSE. It is unclear whether the magnitude of the risk factors identified among infants with PSE are similar to the general population.Additionally, the lack of a control group leaves unanswered an important question: Is prenatal substance exposure itself an independent risk factor for SUID after adjustment for other known confounders? Although previous literature supports such a link, our understanding of confounding factors has advanced. Deutsch identified that 71% of infants with PSE had nicotine exposure, compared with only 31% of unexposed infants. Prenatal and postnatal nicotine exposure significantly increases the risk of SUID.5 Although the exact mechanism is not fully understood, it is proposed that nicotine exposure impairs the brainstem’s protective response to respiratory insults.5 Thus, nicotine exposure may be a critical confounder of SUID risk among infants with PSE. To address issues of residual and unmeasured confounding in previous studies describing an association between SUID and PSE, population-level registries, including large numbers of births, detailed data on social and medical risk factors prenatally and postnatally, and data on SUID cases are needed. However, developing and maintaining such registries poses significant challenges.Finally, the study findings should be interpreted considering the potential influence of missing data, both within data of cases available, as well as relative to the overall population of sleep-related SUID cases. The registry used by Deutsch et al is estimated to encompass ∽40% of SUID cases in the United States.4 However, the southeastern part of the United States, including regions of Appalachia hit hard by the opioid overdose epidemic, are not proportionally represented, potentially underestimating cases of SUID among those with PSE. Additionally, the key field the authors selected to indicate PSE “was the infant/fetus delivered drug exposed” does not delineate type of prenatal substance exposure. Without high-quality information about prenatal exposures, it is unclear as to what the PSE category actually reflects.Overall, regardless of the underlying mechanism of SUID risk among infants with PSE, the findings by Deutsch et al highlight the importance of supporting caregivers of infants with PSE in SUID-reducing strategies including smoking cessation, breastfeeding, and safe sleep practices (supine positioning, room-sharing but not bedsharing, and avoidance of soft bedding or objects in the sleep space).6 There are numerous effective interventions that include educational messaging targeting attitudes and beliefs of new parents.6 However, interventions targeting the unique needs of caregivers with infants with PSE are lacking. Many of these caregivers experience competing priorities related to their own medical and psychiatric care, a lack of social support, and addressing their infants’ ongoing withdrawal symptoms, feeding difficulties and challenging temperaments.7–10 Tailored, supportive, and nonpunitive interventions that address the deleterious influence of stigma toward pregnant and parenting people who use substances are needed to ensure the well-being of families affected by prenatal substance use.

To determine the influence of a state's legal environment and a hospital's Prenatal Substance Exposure (PSE) protocol on physicians' propensity to respond when prenatal substance exposure is suspected. Using a sample of 1367 physicians from every state and the District of Columbia, we formulate a set of linear models to determine the impact of the legal environment and hospital protocol on physicians' response to PSE, the agreement between physicians' perceptions and actual state legal environments, and physicians' motivation to act when PSE is suspected. Both protocol and legal environment showed to be significantly correlated with physicians' propensity to take action when PSE is suspected (p < 0.05). Our analysis shows that physicians prefer a public health (patient-centered) approach to more punitive measures. Our results suggest a policy strategy focused first on enacting laws that would encourage a patient-centered approach, by developing and using hospital protocols to implement state policy, and then on educating physicians about the actual legal environment.

After completing this article, readers should be able to: 1. Describe perinatal and neonatal complications of maternal use of cocaine, alcohol, opiates, and barbiturates in pregnancy. 2. List established cutoffs of conventional immunoassays of urine for common substances of abuse. 3. List the advantages of using meconium testing for substances of abuse. 4. Describe the role of fatty acid ethyl esters in detecting prenatal alcohol exposure. Maternal substance use during pregnancy can have direct consequences on both the developing fetus and the mother and is a significant public health concern. The prevalence of gestational use of drugs of abuse varies, depending on the study population and method of detection, but it generally ranges from 1% to 15%. (1) One of the largest epidemiologic studies conducted in the United States documented that although most pregnant women decrease the use of substances as the pregnancy progresses, a significant proportion of them remain regular users, even in the third trimester (eg, ethanol [13%], cannabis [9.3%], cocaine [10%], and heroin [1%]). (2) Various perinatal and neonatal complications can result from prenatal exposure to common drugs of abuse. (3) The use of cocaine during pregnancy is associated with increased risks of preterm labor, intrauterine growth retardation, and neurobehavioral abnormalities. Heavy alcohol use during pregnancy leads to fetal alcohol spectrum disorder, which is characterized by an array of congenital malformations, central nervous system abnormalities, and neurodevelopmental deficits. Neonates exposed to opiates, alcohol, and barbiturates in utero are at risk of developing neonatal abstinence syndrome, which is characterized by irritability, gastrointestinal dysfunction, respiratory distress, and other nonspecific symptoms. (1) Data in the literature conflict regarding adverse events in the immediate postnatal period that can be attributed to prenatal exposure to other illicit drugs. Thus, early identification of neonates in whom substance exposure is suspected is important for appropriate treatment intervention and …

Children with prenatal substance exposure are at high risk of child protection involvement during infancy. We quantified the risk and timing of child protection system involvement until age 12years among children with and without prenatal substance exposure. A whole-population birth cohort (2007-2018) was assembled from data linked for the New South Wales Child E-Cohort, Australia. The prenatal substance exposure population included children with records indicating prenatal substance exposure in hospital, emergency, mental health outpatient, opioid treatment, and/or child protection reports data. We estimated the risk of child protection responses (screened-in reports, investigations, substantiations, and out-of-home care [OOHC]), and child maltreatment types. 1 161 876 children (17 976 with prenatal substance exposure) and 717 063 mothers were included. By age 1year, 75% of the prenatal substance exposure population born in 2018 had ≥1 screened-in report, 34% ≥1 substantiation, and 20% ≥1 OOHC placement, compared with 4%, 0.8%, and 0.2% of all other children, respectively. By age 12, 90% of the prenatal substance exposure population born in 2007 had ≥1 screened-in report, 61% ≥1 substantiation, and 39% ≥1 OOHC placement, compared with 18%, 5%, and 1% of all other children, respectively. One-half of the prenatal substance exposure population had neglect recorded by age 12. Health and socioeconomic disadvantage were more common among the prenatal substance exposure population. Children with prenatal substance exposure experienced high child protection involvement early in life. Child protection reports represent an opportunity to mobilize nonstigmatizing substance use in pregnancy and antenatal care to prevent escalating child protection interventions.

Through a teratological lens: A narrative review of exposure to stress and drugs of abuse during pregnancy on neurodevelopment

The objective of this study was to test a developmental model of neurobehavioral dysregulation relating prenatal substance exposure to behavior problems at age 7. The sample included 360 cocaine-exposed and 480 unexposed children from lower to lower middle class families of which 78% were black. Structural equation modeling was used to test models whereby prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy, which would predict externalizing and internalizing behavior problems in early childhood. Structural equation models were developed for individual and combined parent and teacher report for externalizing, internalizing, and total problem scores on the Child Behavior Checklist. The goodness-of-fit statistics indicated that all of the models met criteria for adequate fit with 7 of the 9 models explaining 18% to 60% of the variance in behavior problems at age 7. The paths in the models indicate that there are direct effects of prenatal substance exposure on 7-year behavior problems as well as indirect effects, including neurobehavioral dysregulation. Prenatal substance exposure affects behavior problems at age 7 through 2 mechanisms. The direct pathway is consistent with a teratogenic effect. Indirect pathways suggest cascading effects whereby prenatal substance exposure results in neurobehavioral dysregulation manifesting as deviations in later behavioral expression. Developmental models provide an understanding of pathways that describe how prenatal substance exposure affects child outcome and have significant implications for early identification and prevention.

Prenatal substance exposure (PSE) is a known risk factor for negative birth outcomes and long-term health outcomes like neurodevelopmental problems. Children in foster care have increased exposure to PSE and higher proportions of developmental delay compared with the general population. It is unclear whether differences still exist among developmental delay screening among children in foster care with and without PSE. Data were extracted from patient medical records of a primary care clinic for children in foster care between January 1, 2018, and December 31, 2021. Cox proportional hazards regression generated hazard of positive developmental delay screening using the Ages and Stages Questionnaire-3 among those who with and without PSE controlling for sex, race, ethnicity, prematurity, caregiver type, as well as interaction between PSE and prematurity and PSE and race. The sample included 975 patients. 60.4% had PSE, and 62.6% had a positive developmental delay screening at least once. 52.9% were male, and 45.5% were White. Those who had PSE but were nonpremature had 1.14 (95% confidence interval, 1.01-1.29) times the hazard of positive developmental delay screening compared with those without PSE and prematurity. However, those with PSE and prematurity had 2.01 times the hazard of positive developmental delay screening than those without either condition. Children in foster care with PSE are at risk for positive developmental delay screening compared with those without; however, those with both PSE and prematurity are at extra risk. This interaction should be considered when making inferences regarding developmental delay screening in this population.

In 2019, Connecticut became the first state to implement a deidentified notification policy for infants with prenatal substance exposure in response to updated provisions contained in the federal Child Abuse Prevention and Treatment Act (CAPTA) of 1974. Our study aimed to test whether Connecticut's notification policy was associated with an increase in Child Protective Services (CPS) interactions for this population. We analyzed child welfare and vital records over the course of a sixty-six-month time frame starting two years before the policy took effect. We used interrupted time series models to estimate monthly reports to CPS and foster care placements for infants with prenatal substance exposure in Connecticut's eight counties between March2017 and July2022. Reports and foster placements decreased for newborns with prenatal substance exposure after policy implementation. After covariates were controlled for, the adjusted rate of reports per birth decreased by 7percent per month after the policy's implementation. The proportion of prenatal substance exposure reports resulting in foster care placement decreased by 4percent per month. These findings suggest that Connecticut's approach to CAPTA was associated with a reduction in child welfare encounters among infants with prenatal substance exposure.

Context:Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods.Objectives:Our study’s primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure.Methods:We conducted a cross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) Study, a longitudinal neuroimaging study that measures brain morphometry from childhood throughout adolescence. Data were collected from approximately 12,000 children (ages 9 and 10) and parents across 22 sites within the United States. Prenatal opioid, tobacco, and alcohol use was determined through parent self-report of use during pregnancy. We extracted variables assessing the volumetric size (mm3) of the amygdala, hippocampus, and parahippocampal gyrus as well as brain volume, poverty level, age, sex, and race/ethnicity for controls within our adjusted models. We reported sociodemographic characteristics of the sample overall and by children who had PSE. We calculated and reported the means of each of the specific brain regions by substance exposure. Finally, we constructed multivariable regression models to measure the associations between different PSE and the demographic characteristics, total brain volume, and volume of each brain structure.Results:Among the total sample, 24.6% had prenatal alcohol exposure, 13.6% had prenatal tobacco exposure, and 1.2% had prenatal opioid exposure. On average, those with prenatal tobacco exposure were found to have a statistically significant smaller parahippocampus.Conclusions:We found a significant association between prenatal tobacco exposure and smaller parahippocampal volume, which may have profound impacts on the livelihood of individuals including motor delays, poor cognitive and behavioral outcomes, and long-term health consequences. Given the cumulative neurodevelopmental effects associated with PSE, we recommend that healthcare providers increase screening rates, detection, and referrals for cessation. Additionally, we recommend that medical associations lobby policymakers to address upstream barriers to the effective identification of at-risk pregnant individuals, specifically, eliminating or significantly reducing punitive legal consequences stemming from state laws concerning prenatal substance use.

Prenatal substance exposure is associated with abnormal visual evoked potentials in offspring, but whether ocular abnormalities are present past infancy is unclear. We determined the association between prenatal substance exposure and hospitalizations for eye disorders in childhood. We conducted a longitudinal cohort study of 794,099 infants born between 2006 and 2016 in all hospital centers in Quebec, Canada. We identified infants prenatally exposed to opioids, cocaine, cannabis, and other illicit substances and followed them over time to assess eye disorders that required in-hospital treatment, including retinal detachment and breaks, strabismus, and other ocular pathologies. We calculated incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) for the association of prenatal substance exposure with risk of eye disorders, adjusted for patient characteristics. Infants exposed to substances prenatally had a higher incidence of hospitalizations for eye disorders compared with unexposed infants (47.0 vs 32.0 per 10,000 person-years). Prenatal substance exposure was associated with 1.23 times the risk of hospital admission for any eye disorder during childhood compared with no exposure (95% CI 1.04-1.45). Risks were greatest for strabismus (HR 1.55, 95% CI 1.16-2.07) and binocular movement disorders (HR 1.96, 95% CI 1.00-3.83). Opioid use was strongly associated with the risk of ocular muscle disorders (HR 3.15, 95% CI 1.98-5.01). Prenatal substance exposure is significantly associated with future hospitalizations for eye disorders in childhood. Efforts to minimize substance use in women of reproductive age are needed in light of the current opioid epidemic.

Single-substance exposure effects on neurodevelopmental outcomes, such as problem behavior and intelligence quotient (IQ), have been studied in children for decades. However, the long-term consequences of polysubstance exposure are poorly understood. Longitudinal neurodevelopmental data were gathered from cohorts across the United States through the Environmental Influences on Child Health Outcomes Program. Data on prenatal exposure to opioids, nicotine, marijuana, and alcohol were collected from children ages 6 to 11 years (N = 256). Problem behavior was assessed using the Child Behavior Checklist (school-age version), and verbal IQ (VIQ) and performance IQ (PIQ) were assessed using the Weschler Intelligence Scale for Children, Fifth Edition. We first identified latent profiles in the overall sample, then evaluated differences in profile membership for children with and without prenatal substance exposure. Latent profile analysis identified two mutually exclusive categories: average VIQ and PIQ, with typical problem behavior, and below-average VIQ with average PIQ and clinically significant problem behavior. Children with prenatal nicotine and polysubstance exposures were more likely to be classified in the below-average VIQ, elevated problem behavior profile compared with children without prenatal nicotine exposure. The presence of clinically significant behavior problems in children with average PIQ, but below-average VIQ, could represent a unique endophenotype related to prenatal nicotine exposure in the context of other prenatal substance exposures. · The neurodevelopmental consequences of prenatal polysubstance exposure are poorly understood.. · Children with prenatal polysubstance exposure exhibited reduced IQ and elevated problem behavior.. · We found significant behavior problems in children with average PIQ and below-average VIQ.. · This may represent a unique endophenotype related to prenatal nicotine exposure..

Prenatal and postnatal adversities, including prenatal alcohol exposure (PAE), prenatal exposure to other substances, toxic stress, lack of adequate resources, and postnatal abuse or neglect, often co-occur. These exposures can have cumulative effects, or interact with each other, leading to worse outcomes than single exposures. However, given their complexity and heterogeneity, exposures can be difficult to characterize. Clinical services and research often overlook additional exposures and attribute outcomes solely to one factor. We propose a framework for characterizing adverse prenatal and postnatal exposures and apply it to a cohort of 77 children. Our approach considers type, timing, and frequency to quantify PAE, other prenatal substance exposure, prenatal toxic stress, postnatal threat (harm or threat of harm), and postnatal deprivation (failure to meet basic needs) using a 4-point Likert-type scale. Postnatal deprivation and harm were separated into early (<24 months of age) and late (≥24 months) time periods, giving seven exposure variables. Exposures were ascertained via health records, child welfare records, interviews with birth parents, caregivers, and/or close family/friends. Nearly all children had co-occurring prenatal exposures, and two-thirds had both prenatal and postnatal adversities. Children with high PAE were more likely to experience late postnatal adversities, and children with other prenatal substance exposure were more likely to have early postnatal deprivation. Postnatal adversities were more likely to co-occur. This framework provides a comprehensive picture of a child's adverse exposures, which can inform assessment and intervention approaches and policy and will be useful for future research.

Associations between prenatal and postnatal substance exposure and salivary C-reactive protein in early childhood

Mood and neurotic disorders among youth with prenatal substance exposure: A longitudinal register-based cohort study

Our primary objective was to estimate statewide prenatal substance exposure based on umbilical cord sampling. Our secondary objectives were to compare prevalence of prenatal substance exposure across urban, rural, and frontier regions, and to compare contemporary findings to those previously reported. We performed a cross-sectional prevalence study of prenatal substance exposure, as determined by umbilical cord positivity for 49 drugs and drug metabolites, through the use of qualitative liquid chromatography-tandem mass spectrometry. All labor and delivery units in Utah (N=45) were invited to participate. Based on a 2010 study using similar methodology, we calculated that a sample size of at least 1,600 cords would have 90% power to detect 33% higher rate of umbilical cords testing positive for any substance. Deidentified umbilical cords were collected from consecutive deliveries at participating hospitals. Prevalence of prenatal substance exposure was estimated statewide and by rurality using weighted analysis. From November 2020 to November 2021, 1,748 cords (urban n=988, rural n=384, frontier n=376) were collected from 37 hospitals, representing 92% of hospitals that conduct 91% of births in the state. More than 99% of cords (n=1,739) yielded results. Statewide, 9.9% (95% CI 8.1-11.7%) were positive for at least one substance, most commonly opioids (7.0%, 95% CI 5.5-8.5%), followed by cannabinoid (11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) (2.5%, 95% CI 1.6-3.4%), amphetamines (0.9%, 95% CI 0.4-1.5), benzodiazepines (0.5%, 95% CI 0.1-0.9%), alcohol (0.4%, 95% CI 0.1-0.7%), and cocaine (0.1%, 95% CI 0-0.3%). Cord positivity was similar by rurality (urban=10.3%, 95% CI 8.3-12.3%, rural=7.1%, 95% CI 3.5-10.7%, frontier=9.2%, 95% CI 6.2-12.2%, P=.31) and did not differ by substance type. Compared with a previous study, prenatal exposure to any substance (6.8 vs 9.9%, P=.01), opioids (4.7 vs 7.0% vs 4.7%, P=.03), amphetamines (0.1 vs 0.9%, P=.01) and THC-COOH (0.5 vs 2.5%, P<.001) increased. Prenatal substance exposure was detected in nearly 1 in 10 births statewide.