The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants

Abstract Background Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues) in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants. Methods and design Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals, and are randomly assigned to the experimental (Cues) intervention or to an attention control (Care) condition. The Cues intervention teaches mothers to attend to their own physiological, cognitive, and emotional cues that signal anxiety and worry, and to use cognitive-behavioural strategies to reduce distress. Mothers are also taught to understand infant cues and to respond sensitively to those cues. Mothers in the Care group receive general information about infant care. Both groups have 6 contacts with a trained intervener; 5 of the 6 sessions take place during the infant's hospitalization, and the sixth contact occurs after discharge, in the participant mother's home. The primary outcome is maternal symptoms of anxiety, assessed via self-report questionnaire immediately post-intervention. Secondary outcomes include maternal sensitive behaviour, maternal symptoms of posttraumatic stress, and infant development at 6 months corrected age. Discussion The Cues and Care trial will provide important information on the efficacy of a brief, skills-based intervention to reduce anxiety and increase sensitivity in mothers of very low birthweight infants. A brief intervention of this nature may be more readily implemented as part of standard neonatal intensive care than broad-based, multi-component interventions. By intervening early, we aim to optimize developmental outcomes in these high risk infants. Trial Registration Current Controlled Trials ISRCTN00918472 The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infant

Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and Prolactin Knockout Mice.

Prolactin (PRL) is well characterized for its roles in initiation and maintenance of lactation, and it also suppresses stress-induced responses. Feeding a high-fat diet (HFD) disrupts activity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether PRL regulates HPA axis activation under HFD feeding is not clear. Male and female wildtype (WT) and PRL knockout (KO) mice were fed either a standard low-fat diet (LFD) or HFD for 12 weeks. Circulating corticosterone (CORT) levels were measured before, during, and after mice were subjected to an acute restraint stress or remained in their home cages as no stress controls. HFD feeding increased leptin levels, but the increase was lower in KO than in WT mice. All stressed female groups and only LFD-fed stressed males had elevated CORT levels compared to their no stress same-sex counterparts regardless of genotype. These results indicated that HFD consumption blunted the HPA axis response to acute stress in males but not females. Additionally, basal hypothalamic CRH content was lower in HFD than LFD males, but was similar among female groups. Furthermore, although basal CORT levels were similar among KO and WT groups, CORT levels were higher in KO mice than their WT counterparts during stress, suggesting that loss of PRL led to greater HPA axis activation. Basal PRL receptor mRNA levels in the choroid plexus were higher in HFD than LFD same-sex counterparts, suggesting activation of central PRL's action by HFD feeding in both males and females. Current results confirmed PRL's roles in suppression of the stress-induced HPA axis activation. Although HFD feeding activated central PRL's action in both sexes, only the male HPA axis was dampened by HFD feeding

Plasma corticosterone levels.

<p>Circulating corticosterone (CORT) levels of male wildtype (WT) and prolactin knockout (KO) mice fed with a low-fat diet (LFD) (A) or a high-fat diet (HFD) (B), and WT and KO males fed with a LFD (C) or a HFD (D), during 30 min restraint stress (S) or no stress control (NS). Circulating CORT levels of female WT and KO mice fed with a LFD (E) or a HFD (F), and WT and KO females fed with a LFD (G) or a HFD (H), during 30 min restraint stress (S) or no stress control (NS). A, B, E, F: * Different between genotypes with the same stress condition. † Different between stress conditions with the same genotype. C, D, G, H: § Different between diets with the same stress condition. † Different between stress conditions with the same diet. Male: WT LFD/NS n = 13; LFD/S n = 15; HFD/NS n = 13; HFD/S n = 13. KO LFD/NS n = 17; LFD/S n = 15; HFD/NS n = 14; HFD/S n = 16. Female: WT LFD/NS n = 12; LFD/S n = 13; HFD/NS n = 14; HFD/S n = 15. KO LFD/NS n = 13; LFD/S n = 15; HFD/NS n = 12; HFD/S n = 14.</p

Prolactin receptor mRNA levels in the choroid plexus.

<p>Prolactin receptor (PRLR) mRNA levels in the choroid plexus of male (A) and female (B) wildtype (WT) or prolactin knockout (KO) mice fed with a low-fat diet (LFD) or a high-fat diet (HFD). * Different between diets with the same genotype. † Different between genotypes with the same diet.</p

Body weight and caloric intake.

<p>Body weight of male (A) and female (B) and caloric intake of male (C) and female (D) wildtype (WT) or prolactin knockout (KO) mice fed with a low-fat diet (LFD) or a high-fat diet (HFD). * Different from LFD-fed males with the same genotype at the same time points. Male: WT chow n = 28; WT HFD n = 26; KO chow n = 32; KO HFD n = 30. Female: WT chow n = 25; WT HFD n = 29; KO chow n = 28; KO HFD n = 26.</p

Hypothalamic corticotrophin releasing hormone levels.

<p>Hypothalamic corticotrophin releasing hormone (CRH) levels of male (A) and female (B) wildtype (WT) or prolactin knockout (KO) mice fed with a low-fat diet (LFD) or a high-fat diet (HFD). * Different between diets with the same genotype.</p

Body composition and plasma leptin levels.

<p>Body fat mass of male (A) and female (B), lean mass of male (C) and female (D), and circulating leptin levels of male (E) and female (F) wildtype (WT) or prolactin knockout (KO) mice fed with a low-fat diet (LFD) or a high-fat diet (HFD). A: * Different from LFD-fed groups with the same genotype. C: * Different between LFD-fed KO males and HFD-fed KO males at the same time points. E, F: * Different from LFD-fed groups with the same sex and same genotype. † Different from levels in WT groups with the same sex and diet.</p