Following directions, ignoring distractions, and inhibiting inappropriate responses: many aspects of children’s everyday functioning are, in some way, dependent on self-regulation. Self-regulation refers to the ability to automatically or purposely control thoughts, feelings, and behaviors (Karoly, 1993; Nigg, 2017). During the first years of life, self-regulation shows a rapid development and children typically become competent in complex self-regulatory skills, such as executive functioning, around the preschool period (Garon et al., 2008; Hendry et al., 2016). The emergence of self-regulatory skills is crucial for positive child outcomes, including health and well-being across the lifespan (Kopp, 1982; Moffitt et al., 2011). However, not all children develop at the same rate and preschool age children often differ considerably in their self-regulatory skills (Hendry et al., 2016). Given the importance of self-regulatory skills, it is crucial to understand which factors can explain individual differences in self-regulation at such early age (Vink et al., 2020). The emergence of complex self-regulatory skills may be impeded by a host of risk factors, a number of which can already be present in the prenatal caregiving environment. For instance, parental mental health problems (for a meta-analysis, see Power et al., 2021), low parental SES (for a review, see Vukojević et al., 2017), and prenatal stress (Davis et al., 2011; Korja et al., 2017) appear to negatively impact child developmental outcomes, such as self-regulation. Consistent with the cumulative risk hypothesis (Appleyard et al., 2005; Evans et al., 2013), exposure to multiple prenatal risk factors at the same time increases the likelihood of self-regulation deficits in preschool age children (Camerota & Willoughby, 2020). Yet, relatively little work has identified the specific mechanisms linking prenatal exposure to multiple risk factors and child self-regulation later in life. In line with biopsychosocial theories (Calkins et al., 2016; Sameroff, 2009), the current study examines whether psychosocial processes (the development of parenting) and biobehavioral processes (brain maturation) simultaneously mediate the effect of prenatal risk on self-regulation in preschool age children. Psychosocial mechanisms From a psychosocial perspective, it is assumed that positive experiences embedded within the early caregiving environment promote children’s self-regulatory skills (Bernier et al., 2010). Young infants still strongly depend on external regulation from their caregiving environment, but increasingly become more independent and able to achieve complex self-regulatory skills (Kopp, 1982; Lobo & Lunkenheimer, 2020). As parenting behaviors represent the most intense and immediate environmental experiences during early childhood, various theories emphasize the importance of early parent-child interactions that promote positive child outcomes later in life (e.g., Bowlby, 1979; Bronfenbrenner, 1979). Subsequently, empirical work revealed that the experience of supportive, consistent, and appropriate stimulating parenting behaviors are positively related to the emergence of child self-regulatory skills (for reviews, see Fay-Stammbach et al., 2014; Karreman et al., 2006). In general, these positive parenting behaviors appear to be relatively stable across infancy and early childhood (e.g., Dallaire & Weinraub, 2005; Paschall & Mastergeorge, 2018). Prenatal risk factors increase the risk for non-optimal parenting during the first years of life (Guyon-Harris et al., 2021; Tambelli et al., 2014). For instance, prenatal mental health problems (for a review, see Berg-Nielsen et al., 2002) and adverse prenatal live events (Tambelli et al., 2014) are linked to impaired parenting in early childhood, such as problems with recognizing and responding appropriately to children’s signals and needs. Especially exposure to multiple prenatal risk factors appears to negatively affect the quality of parenting behaviors (Barker et al., 2011; Tambelli et al., 2014). Mothers exposed to cumulative risk (e.g., both depressive symptoms and psychosocial risk, such as low educational level and single motherhood) showed lack of reciprocity, more intrusiveness and more conflictual parent-child interactions compared to non-exposed mothers, as well as compared to mothers with solely depressive or solely psychosocial risk (Tambelli et al., 2014). With increasing age, it might become even harder for parents to recognize and appropriately respond to the needs of their children as a result of advances in child mobility and increases in children’s sense of autonomy (Bornstein, 2019). Therefore, exposure to multiple prenatal risk factors might affect children’s self-regulation directly, or indirectly, through a disruption of the quality and the development of parenting. Previous research on postnatal cumulative risk demonstrated that maternal behaviors indeed mediated relations between exposure to cumulative risk and behavioral outcomes in preschool age children, such as aggression and rule-breaking behaviors (Trentacosta et al., 2008), and measures of attention, inhibitory control, and delay ability (Lengua et al., 2007). However, studies examining the mediating effect of parenting quality in the relation between prenatal cumulative risk and child self-regulation are, to our knowledge, still lacking. Although a meta-analysis on the association between exposure to risk (i.e., maternal depression) and child self-regulation revealed that prenatal and postnatal exposure to maternal depressive symptoms had the same negative effect on child self-regulation (Power et al., 2021), the mechanisms underlying the adverse effects of risk factors might be different when considering the timing of exposure to risk factors. Beside the effect of prenatal risk on parenting behaviors (Guyon-Harris et al., 2021; Tambelli et al., 2014), the prenatal period is a critical period for infant’s internal biobehavioral processes, such as neurocognitive development (for a review, see Ruiz et al., 2005). Therefore, it is now increasingly recognized that prenatal exposure to risk factors could alter child developmental outcomes through biobehavioral mechanisms as well (Power et al., 2021; Ruiz et al., 2005). Biobehavioral mechanisms From a biobehavioral perspective, there is growing evidence that self-regulation emerges as a function of brain maturation. For instance, the exchange of information between brain regions within functional networks (e.g., the orienting and executive attention network) appears to play an important role in child self-regulation (Posner & Rothbart, 2000; Rothbart et al., 2011). However, the infants’ brain still consists of an overabundance of neural connections, which hinders optimized communication between widespread brain regions. In order to make the exchange of information more efficient, postnatal brain development typically includes optimization of brain networks through the process of systematic pruning of unimportant connections and the strengthening of important connections (Huang et al., 2015; Yap et al., 2011). This process of increasing functional brain network efficiency possibly allows for more complex behaviors to arise during early childhood (Tau & Peterson, 2010). Prior research revealed associations between brain network efficiency and individual differences in young children’s self-regulation (Fekete et al., 2014; Xie et al., 2019). The efficiency of communication within brain networks can be measured using the synchronicity of oscillatory EEG rhythms, reflecting the communication between distinct brain regions. Small-worldness is one of the most frequently analyzed topological properties of functional brain network efficiency, which calculates the optimization of brain networks by using a graph-theoretical framework (Muldoon et al., 2016). In graph theory, brain networks consist of nodes and edges, respectively reflecting the distributed brain regions and neural connections between these regions (Bassett & Bullmore, 2006; Bullmore & Sporns, 2009). Small-world networks are generally characterized by a high clustering coefficient (dense interconnections between neighboring nodes) in combination with few edges between clusters of nodes, also referred to as short path lengths (Muldoon et al., 2016). In general, functional brain networks in young children become more efficient with age, indicated by increases in the levels of small-worldness (Gao et al., 2017; Hofstee et al., 2022). The prenatal stress literature has linked a wide variety of mothers’ prenatal risk factors with altered brain networks in young children, such as prenatal mental health problems (e.g., Posner et al., 2016; Soe et al., 2018) and increases in the number of stressful live events during pregnancy (e.g., Humphreys et al., 2020; Van den Bergh et al., 2018). As prenatal risk could undermine the emergence of efficient brain networks, there might be an indirect effect of prenatal risk through deficits in the development of efficient brain networks on child self-regulation later in life. Prior research on postnatal risk indeed revealed that variations in functional brain networks mediated the relation between cumulative risk and individual differences in child self-regulation (Pagliaccio et al., 2015). However, longitudinal studies examining the mediating role of brain network efficiency in the link between prenatal risk and self-regulation in early childhood are, to our knowledge, still lacking. The current study In sum, risk factors during pregnancy have been found to negatively affect the emergence of self-regulatory skills in young children (e.g., Korja et al., 2017; Van den Berg et al., 2009). Thus far, most interventions start in early childhood and tend to focus on promoting the parent-child relationship and the quality of parenting behaviors (Allen, 2011). However, if prenatal risk factors already compromise child developmental outcomes, such as self-regulation, then early interventions may be required during pregnancy as well (O’Donnell et al., 2014). In order to improve interventions that promote the emergence of complex self-regulatory skills in young children, more insight into the possible mechanisms underlying the association between exposure to multiple prenatal risk factors and child self-regulation is necessary. The majority of research on the mediating mechanisms of child self-regulation focuses on postnatal risk, rather than prenatal risk (e.g., Lengua et al., 2007; Pagliaccio et al., 2015), or did not examine psychosocial and biobehavioral processes within the same study, so their relative importance could not be determined (e.g., Camerota & Willoughby, 2020). In line with biopsychosocial theory (Calkins et al., 2016; Sameroff, 2009), the current study addresses important gaps in the literature by simultaneously examining (the development of) parenting quality and brain network efficiency as mediating mechanisms underlying the relation between prenatal risk and variations in child self-regulation. In addition, the current study adds to the literature by examining psychosocial and biobehavioral mechanisms using a longitudinal design, allowing for testing developmental changes in parenting behaviors and brain network efficiency over time. Given that evaluating single risk factors may underestimate the impact of prenatal risk on developmental outcomes, a combination of multiple prenatal risk factors will be created by using the approach of cumulative risk models (Appleyard et al., 2005; Evans et al., 2013).