Expansion and Commentary on a Two Generation Approach to Prenatal Opioid Exposure- a commentary on Conradt et al. (2023)

Early child neurodevelopment, including psychopathology, is influenced by a myriad of factors and interactions. These factors are both intrinsic to the caregiver-child dyad such as genetics and epigenetics as well as extrinsic such as social environment and enrichment. Additional layers of complexity may be at play within families with parental substance use, as outlined by Conradt and colleagues in their review article titled “Prenatal Opioid Exposure: A Two-Generation Approach to Conceptualizing Risk for Child Psychopathology.” (Conradt et al.,2023). Conradt and colleagues provide an overarching synthesis of many findings related to substance use that goes beyond the in-utero exposure to the transgenerational interface of pregnancy and early childhood, including biologic sensitivities such as by genetic predisposition, overrepresentation of social risk factors including early adversities of caregivers and poverty, and transgenerational interactional susceptibilities. Altered dyadic interactions may relate to joint changes in neurobehavior and are not isolated from the influence of infant genetics, epigenetics, and environment. The early neurodevelopmental correlates of prenatal substance exposure including risks of childhood psychopathology are then a composite of many different forces. This nuanced reality, described as an “inter-generational cascade,” does not centralize parental substance use or prenatal exposure as a causative moment but positions it within the ecologic milieu of the total lived experience.

Conradt and colleagues offer an important theoretical framework to the complex underpinnings of prenatal substance exposure and a practical model to target dyadic interventions to support family well-being. As pediatricians and investigators caring for families impacted by parental substance use disorder, we aim to highlight and expand on several areas that continue to challenge us in our clinical practice and research including: 1) Limited linked longitudinal maternal-child data to improve the study of factors in the inter-generational cascade associated with prenatal substance use; 2) Pervasive stigma towards pregnant people and parents with substance use disorder, resulting in substantial barriers to treatment engagement and recovery; and 3) The lack of longitudinal systems of care that are strengths-based to improve family well-being after the delivery hospitalization.

Consider the Data Sources:

Conradt et al. describe a number of pre-pregnancy factors that have been shown to associate with less optimal neonatal outcomes and early childhood developmental trajectories including exposure to adverse childhood experiences, housing instability, poverty, as well as maternal genetics and comorbid medical and mental health conditions. When secondary analyses to assess child health outcomes associated with relevant perinatal diagnoses are drawn exclusively from pediatric administrative health data, they lack comprehensive, critical maternal data despite the recognized influence. When administrative maternal health data is available and linked, information regarding timing, frequency, and type of substance exposure should also be queried such as has been modeled by Desai and colleagues for prenatal opioids and other medications dispensed by prescription (Desai et al., 2015). Yet, comparable data on exposure to non-prescribed substances poses additional challenges for investigations, as this information is not available from administrative data. Non-prescribed substances also lack standardized or typical dosing, frequency, and substance composition making it difficult to adequately model the association between non-prescribed exposures and neurodevelopmental outcomes.

Additionally, an intrinsic assumption within the analysis of administrative health data is that the noise of individual variations in medical practice and diagnosis will be cancelled by an overarching shared approach in general, without introducing systematic biases. While this assumption may be appropriate in many circumstances and analyses of administrative health data, it deserves persistent evaluation for substance use and related diagnoses, particularly neonatal opioid withdrawal syndrome (NOWS), given the potential for substantial variability in practice and diagnosis as well as ongoing evolution of syndromic definitions. For example, a standardized clinical definition for neonatal opioid withdrawal syndrome was only proposed in 2022 (Jilani et al., 2022). Following a modified Delphi process with clinical experts, Jilani and colleagues proposed a working definition that requires a known history of prenatal opioid exposure and a distinct set of withdrawal signs for a diagnosis of NOWS. While this standardization is a critical step, it is important to note that this definition does not specify the timing, frequency, and type of opioid exposure (e.g., differentiating between non-prescribed opioids, medications to treat opioid use disorder, or other indications for opioid exposures during pregnancy such as chronic pain).

Thus, secondary analysis of administrative health data remains useful in understanding overarching trends in diagnoses, yet caution must be used to avoid interpretation pitfalls. Without simultaneous, systematic documentation of the many potentially contributing forces outlined by Conradt such as poverty and parental experience of adverse childhood experiences, it remains unclear whether identified concentrations of neurodevelopmental differences in populations of children with documented history of prenatal substance exposure are related directly to the exposure or rather the overrepresentation of other social and environmental burdens within the care environment. Moreover, the clinical decision making underlying the diagnosis code application is completed by providers with individual life experiences, priorities, and, realistically, personal biases operating within varied health system approaches and policies.

Unique Stigma and Discrimination:

Pregnant people and parents with substance use disorders face unique stigma and experiences of discrimination that can impact the developmental milieu of their children during pregnancy, at delivery, and throughout childhood. One potential type of such stigma that may be particularly dangerous for pregnant people and parents with history of substance use is in health-related stigma via their interactions with the healthcare system. Health-related stigma has been defined as “a social process or related personal experience characterized by exclusion, rejection, blame, or devaluation that results from experience or reasonable anticipation of an adverse social judgment about a person or group identified with a particular health problem” (Weiss & Ramakrishna, 2006). A breadth of data has demonstrated that stigma can influence health outcomes given its cross-cutting mechanisms as a negative psychologic force (van Brakel et al., 2019). In this view, stigma can act as a bidirectional barrier to health, decreasing patient engagement while undermining provider efficacy. These simultaneous effects can lead to discriminatory interactions, shared inculcation of pre-conceived stereotypes, and poor health outcomes, advancing the argument that health-related stigma should be considered a social determinant of health. Above and beyond health-related stigma that may be activated in response to substance use in isolation, people who are pregnant may be subject to additional social mores, societal expectations around the expectations of the “good mother” and punitive policies that have been shown to result in avoidance of prenatal care, worse perinatal outcomes, and increased risk of family separation at delivery (Austin et al., 2022; Stone, 2015).

The availability of non-stigmatizing healthcare is especially salient when considering the interface of substance use with pregnancy, childbirth, and infancy. There is robust evidence-base to support medications for opioid use disorder (MOUD) for many in their recovery process, including during pregnancy (Substance Abuse and Mental Health Services Administration, 2018) Yet, safe initiation of MOUD first requires engagement with healthcare, a status likely inverse to experiences of health-related stigma. Relatedly, routine prenatal care has a high rate of healthcare interactions. Deviation from typical prenatal care cadence related to stigma may further exacerbate health disparities and reinforce bidirectional stigmatizing views (Stone, 2015).

After birth, a better understanding of patient and family experience and interventions for addressing health-related stigma are critical to optimize non-pharmacologic infant supports and promote caregiver presence. As outlined by van Brakel and colleagues, potential interventions to address health related stigma include those to support both patients and providers in open and honest engagement including patient empowerment and skill building as well as provider education and exposure to affected populations (van Brakel et al., 2019). Continued engagement with routine pediatric care to support infant development requires ongoing non-stigmatizing relationships. Multiple components of anti-stigma interventions map to potential roles within interdisciplinary clinical teams within which we practice, such as doulas or peer recovery specialists, though empiric research evaluation is needed to assess this potential.

Finally, research and academic pursuits will also benefit from critical appraisal to avoid inadvertent perpetuation of stigma within their own conduct and dissemination. Conradt and colleagues clearly outline the limitations of the current evidence landscape on the putative long-term neurodevelopmental consequences after prenatal substance exposures, given the complicated realities of multidimensional risks and protective factors. Against these limitations, we must be cautious with statements that conclude putative differences such as that children exposed to opioids “often have long-term disruptions in cognitive, behavioral, and perceptual development”. Prospective, multi-dimensional studies such as planned within the NIH HEAL initiative will add important literature base to advance our understanding. Including individuals and families most affected in the design, analysis, and interpretations of future interventions can help ensure recovery informed, non-stigmatizing research practices.

Strengths-Based Longitudinal Supports

The non-pharmacologic care of infants with history of prenatal opioid exposure has increased in prominence and is an important advance in the embedding of a more supportive healthcare approach. There remains a need to push those advances beyond the birth hospitalization and into longitudinal pediatric and parental healthcare settings to address modifiable factors to promote family well-being. Reflecting the generally accepted view of recovery as a longitudinal process, provision of ongoing, non-stigmatizing, recovery-informed pediatric healthcare throughout childhood warrants additional evaluation, investment, and dissemination as best practices are identified. Importantly, there are conceptual frameworks available for supportive caregiver-infant dyadic care that can serve as the foundation for many clinicians to adapt to their own unique settings (Velez et al.,2021).

Strength-based care is an important component of recovery-informed care and can be used to combat the stigma pregnant and parenting people experience. As outlined by Conradt and reiterated above, families with history of substance use often have an inordinate burden of social risks and adverse experiences. Importantly, these risks are not deterministic and should be balanced by accounting for familial strengths and points of resilience. Exemplary family and child strengths that can be named but may be commonly overlooked include commitment to engage in care, attachment between caregiver and infant, and receptiveness to education and improvements. Modeling strength-based interactions for families may have iterative effects on parenting as incorporation of strength-based parenting has demonstrated positive effects on parenting efficacy (Waters & Sun, 2016). Evaluation of such programs with tailoring to support families with history of substance use warrants consideration.

This strength-based approach to interactions should also be considered within research assessments to include explicit annotation of child and family strengths. For example, several scales of benevolent or positive childhood experiences have been developed that are reminiscent yet counter to scales of adverse childhood experiences (Narayan et al., 2018). Multiple studies have demonstrated the buffering effect of benevolent experiences, including when focused on pregnancy. Without inclusion of adequate balance, persistent, isolated documentation of risks and negative outcomes may exacerbate stigma by activating stereotypes and permitting unchecked bias.

Conclusion

In conclusion, as we seek to better understand modifiable points of action within the ecologic milieu of substance use including attendant prenatal substance exposure and its associates in the potential development of child psychopathology, nuanced contextualization with accurate yet balanced approaches are needed to support continued, non-stigmatizing, strength-based advances in the understanding of and care for families with history of substance use.