Martha G. Welch

Calming cycle theory: the role of visceral/autonomic learning in early mother and infant/child behaviour and development

Results from a randomised controlled trial of Family Nurture Intervention (FNI) showed significantly improved maternal behaviours and infant neurodevelopment and behaviour through 18 months, including a significantly reduced risk for autism. Preliminary results from a pilot study of FNI in preschool children found significant reduction in adverse behaviour. Conclusion: Calming cycle theory proposes that early emotional behaviour is shaped by subcortical visceral/autonomic co‐conditioning between mother and infant. Two new constructs, emotional connection and visceral/autonomic co‐regulation, are defined within a functional Pavlovian conditioning framework and are theorised to be part of an evolutionarily conserved mammalian phenomenon first identified by Pavlov.

Nurture in the neonatal intensive care unit.

In their excellent review, Kommers et al. (1) use a novel approach to answer an important question: Why do maternal licking, grooming and separation have such a big effect on bonding? In summarising an impressive body of physiological research, the authors conclude that optimised parent–infant bonding can overcome negative impacts of premature birth, and that such efforts should be increased in the neonatal intensive care unit (NICU). While acknowledging the limitations of Bowlby’s theoretical construct, the authors strive to unite their analyses into it. The authors touch upon the concept of coregulation. However, they limit discussion to regulation of the infants by their mothers. In fact, the infant also regulates the mother’s physiology (e.g. suckling-related oxytocin release, skin temperature during skin-to-skin holding, physiological responses to crying). Co-regulation between mother and infant in close physical contact during nurture activities, such as holding and nursing, has survival advantage and serves to maintain homoeostasis in both. Clinical observations during family nurture interventions led me to the conclusion that the static psychological constructs of ‘bonding’ do not adequately describe the normal, dynamic mother–infant relationship. Rather, I view biological co-regulation as underlying the formation and maintenance of an emotional connection between the two. In this light, I was able to understand dysregulated behaviour as being related to the absence of co-regulation, and thereby formulate a clear path to its remedy. Mothers can be ‘bonded’ to their infants, but not necessarily spend significant time in states of co-regulation and emotional connectedness. This leaves the child vulnerable to dysregulation. Despite identifying the existence of co-regulation of the infant by the mother, bonding theorists place an emphasis on self-regulation, a state that too often dissolves into dysregulation, which interferes with energy homoeostasis, optimal learning and interrelating. Morelius posits that shared environment increases concordance of the pair’s hypothalamic pituitary adrenal (HPA) axis reactivity (2). Nonetheless, sharing an environment does not in itself guarantee co-regulation of physiological states. In our randomised control NICU trial of the Family Nurture Intervention, many mothers were judged to be emotionally disconnected (e.g. visibly removed or distracted from the infant during skin-to-skin contact). However, asking the mothers to express their emotional upset directly to their infants was repeatedly observed to result in dramatic changes in behavioural states in both infant and mother. Hearing the mother’s expression of upset emotion, infants often became alert and made eye contact. The mothers typically responded with enlivened engagement and expressed feeling a deep connection, often for the first time. More useful to NICU neonatologists, nurses and parents are three questions: (i) Are the mother and infant coregulating and emotionally connected? (ii) Upon emotional upset, how easily do the mother and infant regain this connection? (iii) How can a mother–infant pair achieve/ maintain emotional connection? Meeting one another’s needs is key to emotional connection. Our hypothesis is that infants with met needs have increased co-regulation with their mothers and less dysregulation when the mother is absent. Establishment of a Calming Cycle routine, during which the pair achieves a state of mutual calm and co-regulation, is the target of Family Nurture Intervention. The nurture science field struggles to explain mother– child interactions within Bowlby’s psychological, central nervous system framework. It is clear that early experiences can affect the hypothalamic–pituitary–adrenal axis, but we may better understand the underlying mechanisms by studying early life experiences at the level of subcortical, hormonal and autonomic nervous system (ANS) activities. Kommers and co-authors cite Hofer’s ‘hidden regulators’ (3) and the licking and grooming methylation research of Meaney and colleagues (4) to explain the nurture phenomenon. I agree that these are examples of basic behavioural and molecular mechanisms that underlie the powerful effects of nurture. However, I believe these mechanisms exert their actions at the subcortical rather than psychological cortical levels. Thepowerful physiological effects ofNICUhospitalisation on themother and baby, as documented byGrunau et al. (5), are best understood in the context of subcortical emotional connection and co-regulation. Fundamentally, the evolutionarily conserved Pavlovian-conditioning mechanism effects on bodily functions result in high/low survival and adaptive/maladaptive behaviours. This conditioning mechanism, which begins in utero and continues after birth, assures survival and adaptive behaviour. Pavlovian conditioning may be the foundational mechanism underlying

Colostrum oxytocin modulates cellular stress response, inflammation, and autophagy markers in newborn rat gut villi

Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase). We also measured two inflammation-signaling proteins NF-κB and its inhibitor IκB. To test the impact of colostrum on autophagy, we measured a marker of autophagy initiation, LC3A. Colostrum increased inactive p-eIF2a, p-PKR and IκB and reduced p-IκB, BiP and LC3A. LPS increased and OT decreased p-IkB. BiP (GRP78) was higher in unprimed than primed villi. Together, these data suggest that colostrum OT attenuates the impact of inflammation on postnatal gut villi and that OT enhances autophagy to protect against amino acid insufficiency-induced stress during the interval between birth and the first feeding.

Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis

Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Genetic deletion of the 5-HT transporter (SERT), which increases and prolongs effects of 5-HT, was found to increase the severity of systemic manifestations, intestinal inflammation, and associated hepatotoxicity of experimental NEC. In contrast, genetic deletion of tryptophan hydroxylase 1 (TPH1), which is responsible for 5-HT biosynthesis in enterochromaffin (EC) cells of the intestinal mucosa, and TPH inhibition with LP-920540 both decrease the severity of experimental NEC in the small intestine and liver. These observations suggest that 5-HT from EC cells helps to drive the inflammatory damage to the gut and liver that occurs in the murine NEC model. Administration of OT decreased, while the OT receptor antagonist atosiban exacerbated, the intestinal inflammation of experimental NEC. Data from the current investigation are consistent with the tested hypotheses-that the enteric signaling molecules, 5-HT (positively) and OT (negatively) regulate severity of inflammation in a mouse model of NEC. Moreover, we suggest that mucosally restricted inhibition of 5-HT biosynthesis and/or administration of OT may be useful in the treatment of NEC.NEW & NOTEWORTHY Serotonin (5-HT) and oxytocin reciprocally regulate the severity of intestinal inflammation and hepatotoxicity in a murine model of necrotizing enterocolitis (NEC). Selective depletion of mucosal 5-HT through genetic deletion or inhibition of tryptophan hydroxylase-1 ameliorates, while deletion of the 5-HT uptake transporter, which increases 5-HT availability, exacerbates the severity of NEC. In contrast, oxytocin reduces, while the oxytocin receptor antagonist atosiban enhances, NEC severity. Peripheral tryptophan hydroxylase inhibition may be useful in treatment of NEC.

Family nurture intervention for preterm infants facilitates positive mother–infant face-to-face engagement at 4 months.

Although preterm infants are at risk for social deficits, interventions to improve mother–infant interaction in the neonatal intensive care unit (NICU) are not part of standard care (SC). Study participants were a subset from a randomized controlled trial of a new intervention for premature infants, the Family Nurture Intervention (FNI), designed to help mothers and infants establish an emotional connection. At infants’ 4 months corrected age, mother–infant face-to-face interaction was filmed and coded on a 1-s time base for mother touch, infant vocal affect, mother gaze, and infant gaze. Time-series models assessed self- and interactive contingency. Comparing FNI to SC dyads, FNI mothers showed more touch and calmer touch patterns, and FNI infants showed more angry-protest but less cry. In maternal touch self-contingency, FNI mothers were more likely to sustain positive touch and to repair moments of negative touch by transitioning to positive touch. In maternal touch interactive contingency, when infants looked at mothers, FNI mothers were likely to respond with more positive touch. In infant vocal affect self-contingency, FNI infants were more likely to sustain positive vocal affect and to transition from negative to positive vocal affect. In maternal gaze interactive contingency, following infants’ looking at mother, FNI mothers of male infants were more likely to look at their sons. In maternal gaze self-contingency, following mothers’ looking away, FNI mothers of male infants were more likely to look at their sons. Documentation of positive effects of the FNI for 4-month mother–infant face-to-face communication is useful clinically and has important implications for an improved developmental trajectory of these infants.

The Welch Emotional Connection Screen: validation of a brief mother-infant relational health screen

The Welch Emotional Connection Screen (WECS), assesses mother–infant Emotional Connection in clinical settings. It includes: Attraction, Vocal Communication, Facial Communication, Sensitivity/Reciprocity and clinical decision of Emotional Connection (yes/no). We tested concurrent and construct validity of the WECS and associations with behavioural and physiological measures in preterm infants.

Increased trophoblast inclusions in placentas from prematurely born infants: A potential marker of risk for preterm neurodevelopmental outcomes

Trophoblast inclusions (TIs) are placental abnormalities of the trophoblast bilayer. Present in 2-8% of full-term placentas, they are associated with poor neurodevelopment, including autism. Although previously unstudied, examination of chorionic villi from 108 preterm births revealed a ∼4 fold increase in the frequency of TIs (30.5%). Frequency of TIs was inversely related to gestational age (GA); 43% of placentas <30 weeks and 20% of placentas ≥32 weeks had TIs (χ2xa0=xa04.41, pxa0=xa00.036). This increased prevalence in preterm infants suggests that TIs may indicate adverse intrauterine processes or undetected genetic abnormalities and could identify infants at risk for poor neurodevelopment.

Mother/Infant Emotional Communication Through the Lens of Visceral/Autonomic Learning

Introduction: The benefits of early mother/infant vocal communication are widely acknowledged, but the mechanisms underlying the phenomenon remain unclear.