The U.S. opioid crisis has resulted in a widespread public health problem affecting many populations, including birthing persons and their infants. The incidence of maternal opioid use disorder (OUD) and neonatal abstinence syndrome (NAS; signs of withdrawal following in utero exposure to opioids and other substances) increased by 4.6 and 3.3 per 1,000 birth hospitalizations, respectively, from 2010 to 2017 (1). Although the well-being of birthing persons is essential to the health and development of their infants, many barriers exist to care for pregnant and postpartum persons with OUD. This includes a lack of support/care for the child and access to medications for OUD (MOUD) despite evidence supporting their use in pregnancy (2–4). Such access is important as previous findings have shown that while MOUD can increase the severity of NAS, they reduce overdose death and preterm birth (5, 6). While the interdependence of birthing persons and their infants are recognized, often care is structured such that parents and children are treated as individual and disconnected entities. Such action can lead to higher health care costs, poorer outcomes for parents and children, and missed opportunities for prevention and early intervention.

In view of addressing these care gaps, there is growing support for a dyadic-centered approach to care for substance-exposed birthing persons and infants (7–10). Given the inextricable link between birth persons and their infants, such an integrated approach, considering the needs of both, offers an essential strategy for clinical, surveillance, and research considerations. The definition of a dyad and the study of dyadic relationships has received decades of attention in the developmental literature. DW Winnicott (11) maintained that there is “no such thing as a baby; a baby is a part of a dyadic unit”. Attachment theory (Bowlby) (12) stressed the psychological interplay between parent and child and attunement (Stern) (13) emphasized the intersubjective relationship between the dyad's components. Yet when one aspect of the dyad struggles with a substance use disorder, mental health concerns, or any condition that affects the ability to function as a connected caregiver, these theoretical paradigms become skewed. Therefore, the operationalizing of this work at the bedside for providers from different fields of medicine and in policy research is of paramount importance. However, this has received little attention. Evidence-based criteria and/or consensus guidelines remain limited not only for the clinician, but also across surveillance and research pathways. Thus, what constitutes optimal dyadic care can vary significantly among providers, public health professionals, and researchers. More fundamentally, the concept of the dyad itself can vary in definition, breadth, and scope well beyond the birth relationship (i.e., parent-infant; caregiver-child, any two-person group)—prompting a need for foundational guidance that establishes how the dyad is defined, especially at the clinical bedside. Accordingly, the purpose of this study was to examine how the opioid-exposed birthing person-infant dyad has been defined in clinical research with an overarching goal of informing the development of a clinical definition that may be applicable to public health data collection and research considerations.

The current study applied the RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM) approach to the literature review. (14), This approach has been applied in numerous studies, particularly for questions with similar limitations in evidence-based criteria guiding practice (10, 15). Distinct from statistical methods used in meta-analyses, a RAM literature review enables integration of expert input with synthesis of existing literature to address key knowledge gaps (14). Accordingly, this RAM literature review was conducted by a Federal Steering Committee (FSC; a convened group of staff representing multiple federal agencies) together with an Expert Panel (EP) assembled to examine available literature with the following objectives: (1) summarize how the birthing person-infant dyad has been defined/described across the clinical research spectrum with a focus on exposure to opioids with/without other psychotropic substances, (2) synthesize knowledge gaps in definitional/descriptive criteria, and (3) identify key elements that may address definitional gaps. Together, these findings were used to derive a recommended clinical definition for the opioid-exposed birthing person-infant dyad that can be applied in the surveillance and research settings serving this population.

Despite an emphasis on the dyad, 70% (77/110) of articles identified did not include a definition, description, or criteria for the dyad. While no definition was given, the terms dyad and pair were most often referenced to discuss the study population and/or design (e.g., inclusion/exclusion criteria, methodological design) (n = 65) (Figure 1). The other articles that met exclusion criteria discussed a dyadic approach to care for opioid-exposed birthing persons and their infants (n = 8) and dyadic outcomes (n = 4) without defining the term dyad.

The remaining 30% (33/110) of articles with a focus on the dyad included a description for the dyad beyond its use to reference the birthing person and infant. A structured full-text review of these articles revealed 3 topical categories focused on dyadic outcomes: (1) types of birthing person-infant support, (2) presence or types of opioid/substance exposure and care recommendations, and (3) maternal psychiatric illness and opioid/substance use. For topic group 1, 21 articles focused on MOUD, mental health therapies including psychotherapy, outpatient or residential substance treatment program, parent-infant interactions, and NAS management or other dyadic assessment/intervention programs (data not shown). For topic group 2, 7 articles focused on MOUD, mental health risk factors, family and legal considerations, parent-infant interactions, clinical management of NAS, and the effects of breastfeeding. For topic group 3, 5 articles focused on examination of parent-infant interactions and psychosocial risk factors.

Across these topical groups, a range of literature focusing on the opioid-exposed dyad was noted spanning 1982–2022 with gaps between publication years (without date filters applied in the keyword search), indicating a limitation in the availability of literature (Supplementary Table S1). A compilation of data was constructed with descriptive references to the dyad and thematically analyzed. Authors then identified key recurring elements as descriptive for the dyad. Descriptive elements identified were: (1) engagement; time spent participating in an interactive partnership, (2) communication; the conscious and subconscious interactions between a birthing person and infant, (3) bonding; feelings and emotions from the birthing person toward the infant, (4) attachment; early relationship development—the emotional connection and bond formed between birthing person and infant that provides the foundation for the infant’s emotional development, (5) mutual responsiveness; both birthing person and infant's influence on each other's emotions and behaviors as they grow together, (6) reciprocity; reciprocal social interactions between birthing person and infant, (7) synchrony; shared interest and behaviors that promote a mutually rewarding interaction, (8) attunement; the sharing of emotional experiences during interactions between birthing person and infant; empathy (12, 17–27).

Topic group 1 articles highlighted all descriptive elements outlined; group 2 articles included engagement, communication, attachment, responsiveness, and synchrony; group 3 articles included responsiveness and reciprocity (Figure 2). Individually, each element describes distinct aspects of the birthing person-infant dynamic from birth and spans the breadth of infant development; each element presents concepts identified in the literature as necessary for an understanding of characteristics essential to the dyad. Synthesis of these identified elements revealed one concept integral to the opioid-exposed dyad: the interactional relationship between birthing person and infant as the foundational concept that ties all eight elements together. Together, these findings were applied to delineate the relationship between the opioid-exposed birthing person and infant as definitional for the dyad, with eight characteristics descriptive of this unique relationship (Figure 2, Table 1).

A focus on the opioid-exposed dyad is critically important as the wellbeing of both birthing person and infant directly influences one another, including considerations of short and longer-term health outcomes (28). Although the dyad is intuitively understood as important and appears as a term throughout the published literature, the present findings suggest that it is not always defined when used and any descriptions can vary significantly.

Notably of the 110 articles identified with a focus on the opioid-exposed dyad, no articles contained a specific definition, either formal or operative. Although the primary emphasis was on identifying criteria and/or definitions, articles with a referenced description of the dyad were included in this literature review. Unexpectedly, 70% of articles identified with a focus on the dyad did not include a description beyond a reference to the dyad as a birthing person and infant (or related terms, e.g., mother-infant). However, the remaining 30% of articles illustrated key descriptive elements that can be used to characterize the dyad. Synthesis of these findings revealed one concept integral to defining the dyad, the interactional relationship between the birthing person and infant. This is highlighted by integration of the eight key elements identified: engagement, communication, bonding, attachment, (mutual) responsiveness, reciprocity, synchrony, and attunement. Although bonding reflects a directionality in the interaction from birthing person towards infant, it is an essential component in the foundation of this relationship.

These eight elements have been prominently discussed in the literature for decades—spanning maternal-child health, child development, education, and psychology (12, 17–27, 29). The current recommendations represent the first application and integration of these distinct elements to clinically define the opioid-exposed dyad. Notably, they present a concept shift from the opioid-exposed dyad historically representing a linkage between two individual patient populations to an emphasis on their underlying relationship. Such a shift in focus that emphasizes the relationship as definitional for the dyad can not only inform clinical care at the bedside for birthing persons and their infants, but also public health data collection and research aimed to improve short- and long-term outcomes.

Given the perinatal scope of this analysis, the criteria developed here focus on opioid-exposed dyads. However, synthesis of the elements identified during this literature review that support these recommendations suggest applicability to other dyadic populations including non-opioid substance exposures which were included as polysubstances in this analysis. Likewise, these recommendations could be applicable beyond infancy for prenatally opioid-exposed children, which were also included in this study.

Application of these recommendations to non-opioid/substance exposed populations merits further consideration. Although the recommendations were derived from literature on opioid exposure, clinical consideration of the dyad as a relationship prioritizes the interaction between birthing person and infant regardless of the presence and/or type of exposures. Thus, it is noteworthy that while developed specifically for opioid-exposed birthing person-infant dyads, these recommendations bear consideration with respect to clinical care for non-exposed dyads. Specific to opioid-exposed populations, it is important to better understand how the exposure affects the interactional dynamic between birthing persons and their infants. Emphasis on addressing this question—while considering the distinct clinical and social needs of birthing persons and infants—is fundamental to the development of a dyadic-centered approach to care.

Recent recommendations for dyadic-centered care for opioid-exposed birthing persons and their infants highlight the need to establish how the dyad is defined at the bedside (7–10). Although the concept of the dyad has typically indicated a linkage of two individual patient populations, a better understanding of what this constitutes from a clinical perspective remains limited. The absence of more definitive data has contributed to variability in the development and implementation of a dyadic care approach, with downstream effects on the birthing person and infant, public health data collection, and research efforts. A shift in focus to the dyad as a relationship as presented here can inform a dyadic care approach across these domains: (1) clinical practice; with an emphasis on understanding clinical and social needs specific to improvement of the interactional dynamic between birthing person and infant (e.g., to tailor supportive service linkage to address specific wraparound needs) as opposed to addressing the needs of one or the other aspect of the dyad (e.g., providing simultaneous care to the dyad, addressing the health care needs of each, while contemporaneously evaluating and assisting the interactional capacities of the pair). Such a model could be cost effective—with one healthcare setting for both—and provide superior care in the short and long term, as dyadic interaction/communication is related to child development and maternal parenting capacities for the child, (2) surveillance; with an emphasis on public health issues pertinent to supporting the dyadic relationship through data collection that informs health and supportive programs (e.g., standardization of protocols, metrics specific to public health follow-up, the linkage of child and parent in the derivation of public health policy), and (3) research; with an emphasis on better understanding the dynamics of the dyadic relationship through clinical studies with consistency in inclusion criteria and outcome measures (e.g., short- and long-term outcomes for the dyad as opposed to the individual components). Altogether, a consistent definition addresses a key knowledge gap in the development of dyadic-centered care.

This literature review is subject to limitations inherent of a non-systematic review. While an internal fidelity process was developed to minimize inter-reviewer differences, introduction of reviewer bias may have influenced the findings. The keyword search was informed by an environmental scan and developed using a comprehensive approach applying both historical and new terminology in the field. Nonetheless it may have missed articles for inclusion. Additionally, the literature review was specifically designed with a focus on the perinatal period, by concentrating on articles inclusive of the birthing person and infant relationship (birth to age one year). While it is conceivable that a similar dyadic relationship could be applicable to older children who had been exposed to parental opioid/substance use during pregnancy, current recommendations are specific to infants as is consistent within the scope of the infant-specific dyadic characteristics (e.g., bonding, attachment) identified from this literature review. It is also possible that beyond the birthing person-infant dyad, a focus on this interactional relationship is one that can be applied to infants with other primary caregivers such as family members and foster or adoptive parents. However, given the study's scope on prenatal exposures, this conclusion is not one that can be made from these findings, but one that merits future research.

This literature review identified eight descriptive elements characteristic of the birthing person-infant dyad: engagement, communication bonding, attachment, responsiveness, responsiveness, synchrony, attunement. By integrating these elements, a clinical definition of the dyad was developed based on one fundamental principle, the interactional relationship between the birthing person and infant. This definition shifts the concept of the opioid-exposed dyad from a linkage between two individual patient populations to an emphasis on their underlying relationship. Created for clinical use, this definition can inform development of a dyadic-centered approach to care with downstream public health data and research considerations for this vulnerable population.