Neurophysin I is an analytically robust surrogate biomarker for oxytocin.

Oxytocin is a pleiotropic neuropeptide that plays roles in biological processes ranging from birth, lactation, and social bonding to immune function, cardiovascular repair, and regulation of appetite. Although measurements of endogenous oxytocin concentrations have been performed for more than 50 years, the ability to measure oxytocin accurately poses notable challenges. One potential solution for overcoming these challenges involves measurement of oxytocin's carrier molecule - neurophysin I (NP-1) - as a surrogate biomarker. NP-1 is secreted in equimolar concentrations with oxytocin but has a longer half-life, circulates in higher concentrations, and can be measured using a sandwich immunoassay. We report experiments that 1) analytically validate a commercially available NP-1 sandwich immunoassay for use with human plasma and urine samples, 2) confirm the specificity of this assay, based on detection of NP-1 in plasma from wild-type but not oxytocin knockout mice, 3) demonstrate that NP-1 concentrations are markedly elevated in late pregnancy, consistent with studies showing substantial increases in plasma oxytocin throughout gestation, and 4) establish strong correlation between NP-1 and plasma oxytocin concentrations when oxytocin is measured in extracted (but not non-extracted) plasma. The NP-1 assay used in this study has strong analytical properties, does not require time-intensive extraction protocols, and the assay itself can be completed in < 2 h (compared to 16-24 h for a competitive oxytocin immunoassay). Our findings suggest that much like copeptin has become a useful surrogate biomarker in studies of vasopressin, measurements of NP-1 have similar potential to advance oxytocin research.

Relationship between mother-infant mutual dyadic responsiveness and premature infant development as measured by the Bayley III at 6 weeks corrected age.

BACKGROUND: The quality of mother-preterm infant interaction has been identified as a key factor in influencing the infant's later development and language acquisition. The relationship between mother-infant responsiveness and later development may be evident early in infancy, a time period which has been understudied. AIM: Describe the relationship between mother-infant mutual dyadic responsiveness and premature infant development. DESIGN: This study employed a secondary analysis of data from the 6-week corrected age (CA) follow-up visit of the Hospital-Home Transition: Optimizing Prematures' Environment (H-HOPE) study, a randomized clinical trial testing the efficacy of a mother- and infant- focused intervention for improving outcomes among premature infants. SUBJECTS: Premature infants born between 29 and 34 weeks gestational age and their mothers who had social-environmental risks. OUTCOME MEASURES: At 6-weeks corrected age, a play session was coded for the quality of mutual responsiveness (Dyadic Mutuality Code). Development was assessed via the Bayley Scales of Infant and Toddler Development, 3rd edition. RESULTS: Of 137 mother-infant dyads, high, medium and low mutual responsiveness was observed for 35.8%, 34.3% and 29.9%, respectively. Overall motor, language and cognitive scores were 115.8 (SD = 8.2), 108.0 (7.7) and 109.3 (7.9). Multivariable linear models showed infants in dyads with high versus low mutual responsiveness had higher scores on the motor (ß = 3.07, p = 0.06) and language (ß = 4.47, p = 0.006) scales. CONCLUSION: High mutual responsiveness in mother-premature infant dyads is associated with significantly better language development and marginally better motor development.

Maternal weight status and responsiveness to preterm infant behavioral cues during feeding.

BACKGROUND: Parental obesity is highly predictive of child obesity, and preterm infants are at greater risk of obesity, but little is known about obese and non-obese mothers' responsiveness to preterm infant cues during feeding. The relationship between maternal weight status and response to preterm infant behavioral cues during feeding at 6-weeks corrected age was examined. METHODS: This secondary analysis used data from a randomized clinical trial. Maternal weight was coded during a play session. Mother-infant interaction during feeding was coded using the Nursing Child Assessment Satellite Training Feeding Scale (NCAST). We used multivariate linear regressions to examine NCAST scores and multivariate logistic regressions for the two individual items, satiation cues and termination of feeding. RESULTS: Of the 139 mothers, 56 (40.3%) were obese, two underweight women were excluded. Obese mothers did not differ from overweight/normal weight mothers for overall NCAST scores, but they had higher scores on response to infant's distress subscale (mean = 10.2 vs. 9.6, p = 0.01). The proportion of infants who exhibited satiation cues did not differ by maternal weight. Obese mothers were more likely than overweight/normal weight mothers to terminate the feeding when the infant showed satiation cues (82.1% vs. 66.3%, p = 0.04, adjusted OR = 2.31, 95% CI = 0.97, 5.48). CONCLUSIONS: Limitations include lack of BMI measures and small sample size. Additional research is needed about maternal weight status and whether it influences responsiveness to preterm infant satiation cues. Results highlight the need for educating all mothers of preterm infants regarding preterm infant cues. TRIAL REGISTRATION: NCT02041923 . Feeding and Transition to Home for Preterms at Social Risk (H-HOPE). Registered 15 January 2014.

A Test of Kangaroo Care on Preterm Infant Breastfeeding.

OBJECTIVE: To test the effects of kangaroo care (KC) on breastfeeding outcomes in preterm infants compared with two control groups and to explore whether maternal-infant characteristics and the mother's choice to use KC were related to breastfeeding measures. DESIGN: Secondary analysis of a multisite, stratified, randomized three-arm trial. The treatment groups used KC, auditory-tactile-visual-vestibular (ATVV) intervention, or received preterm infant care information. SETTING: Neonatal intensive care units from 4 hospitals in the United States from 2006 to 2011. PARTICIPANTS: Racially diverse mothers (N = 231) and their preterm infants born weighing less than 1,750 g. METHODS: Mothers and their infants were enrolled once the infants were no longer critically ill, weighed at least 1,000 g, and could be safely held outside the incubator by parents. Participants were instructed by study nurses; those allocated to the KC or ATVV groups were asked to engage in these interactions with their infants for a minimum of 3 times a week in the hospital and at home until their infants reached age 2 months adjusted for prematurity. RESULTS: Feeding at the breast during hospitalization, the duration of postdischarge breastfeeding, and breastfeeding exclusivity after hospital discharge did not differ statistically among the treatment groups. Regardless of group assignment, married, older, and more educated women were more likely to feed at the breast during hospitalization. Mothers who practiced KC, regardless of randomly allocated group, were more likely to provide their milk than those who did not practice KC. Breastfeeding duration was greatest among more educated women. CONCLUSION: As implemented in this study, assignment to the KC group did not appear to influence the measured breastfeeding outcomes.

Beyond Cervical Length: A Pilot Study of Ultrasonic Attenuation for Early Detection of Preterm Birth Risk.

The purpose of this study was to determine whether cervical ultrasonic attenuation could identify women at risk of spontaneous preterm birth. During pregnancy, women (n = 67) underwent from one to five transvaginal ultrasonic examinations to estimate cervical ultrasonic attenuation and cervical length. Ultrasonic data were obtained with a Zonare ultrasound system with a 5- to 9-MHz endovaginal transducer and processed offline. Cervical ultrasonic attenuation was lower at 17-21 wk of gestation in the SPTB group (1.02 dB/cm-MHz) than in the full-term birth groups (1.34 dB/cm-MHz) (p = 0.04). Cervical length was shorter (3.16 cm) at 22-26 wk in the SPTB group than in the women delivering full term (3.68 cm) (p = 0.004); cervical attenuation was not significantly different at this time point. These findings suggest that low attenuation may be an additional early cervical marker to identify women at risk for SPTB.

Relationships among psychosocial factors, biomarkers, preeclampsia, and preterm birth in African American women: a pilot.

AIM: To explore the relationships among psychosocial factors (optimism, uncertainty, social support, coping, psychological distress), biomarkers (cortisol, cytokines), preeclampsia, and preterm birth in African American women. METHODS: Forty-nine pregnant African American women completed psychosocial questionnaires and had blood collected for biomarkers between 26 and 36 weeks of gestation. Birth outcomes were obtained from birth records. RESULTS: Women reporting higher levels of social support had lower levels of pro-inflammatory cytokines (IL-2, IL-5, and IL-6). Surprisingly, compared with low-risk pregnant women, women diagnosed with preeclampsia reported more optimism and less avoidance, and had lower levels of cortisol and IFN-γ. Similarly, compared to women with full-term birth, women with preterm birth reported higher levels of optimism and lower levels of avoidance, and had lower levels of IL-10. CONCLUSION: Psychosocial factors influence inflammation and pregnancy outcomes. Close assessment and monitoring of psychosocial factors may contribute to improved pregnancy outcomes.

Maternally administered interventions for preterm infants in the NICU: effects on maternal psychological distress and mother-infant relationship.

Although studies have examined the effects of interventions focused on preterm infants, few studies have examined the effects on maternal distress (anxiety, depressive symptoms, post-traumatic stress symptoms, parenting stress) or parenting. This study examined the effects of the auditory-tactile-visual-vestibular (ATVV) intervention and kangaroo care (KC) on maternal distress and the mother-infant relationship compared to an attention control group. 240 mothers from four hospitals were randomly assigned to the three groups. Maternal characteristics in the three groups were similar: 64.1% of ATVV mothers, 64.2% of KC mothers, and 76.5% of control mothers were African American; maternal age averaged 26.3 years for ATVV mothers, 28.1 for KC mothers, and 26.6 for control mothers; and years of education averaged 13.6 for ATVV and KC mothers, and 13.1 for control mothers. Mothers only differed on parity: 68.4% of ATVV and 54.7% of KC mothers were first-time mothers as compared to 43.6% of control mothers. Their infants had a similar mean gestational ages (27.0 weeks for ATVV, 27.2 for KC, and 27.4 for control) and mean birthweights (993 g for ATVV, 1022 for KC, and 1023 for control). Mothers completed questionnaires during hospitalization, and at 2, 6 and 12 months corrected age on demographic characteristics, depressive symptoms, state anxiety, post-traumatic stress symptoms, parenting stress, worry about child health, and child vulnerability (only at 12 months). At 2 and 6 months, 45-min videotapes of mother-infant interactions were made, and the HOME Inventory was scored. Behaviors coded from the videotapes and a HOME subscale were combined into five interactive dimensions: maternal positive involvement and developmental stimulation and child social behaviors, developmental maturity, and irritability. Intervention effects were examined using general linear mixed models controlling for parity and recruitment site. The groups did not differ on any maternal distress variable. Kangaroo care mothers showed a more rapid decline in worry than the other mothers. The only interactive dimensions that differed between the groups were child social behaviors and developmental maturity, which were both higher for kangaroo care infants. Change over time in several individual infant behaviors was affected by the interventions. When mothers reported on the interventions they performed, regardless of group assignment, massage (any form including ATVV) was associated with a more rapid decline in depressive symptoms and higher HOME scores. Performing either intervention was associated with lower parenting stress. These findings suggest that as short-term interventions, KC and ATVV have important effects on mothers and their preterm infants, especially in the first half of the first year.

Stressors, resources, and stress responses in pregnant African American women: a mixed-methods pilot study.

This research aimed to develop an initial understanding of the stressors, stress responses, and personal resources that impact African American women during pregnancy, potentially leading to preterm birth. Guided by the ecological model, a prospective, mixed-methods, complementarity design was used with 11 pregnant women and 8 of their significant others. Our integrated analysis of quantitative and qualitative data revealed 2 types of stress responses: high stress responses (7 women) and low stress responses (4 women). Patterns of stress responses were seen in psychological stress and cervical remodeling (attenuation or cervical length). All women in the high stress responses group had high depression and/or low psychological well-being and abnormal cervical remodeling at one or both data collection times. All but 1 woman had at least 3 sources of stress (racial, neighborhood, financial, or network). In contrast, 3 of the 4 women in the low stress responses group had only 2 sources of stress (racial, neighborhood, financial, or network) and 1 had none; these women also reported higher perceived support. The findings demonstrate the importance of periodically assessing stress in African American women during pregnancy, particularly related to their support network as well as the positive supports they receive.

Salivary cortisol and behavioral state responses of healthy newborn infants to tactile-only and multisensory interventions.

OBJECTIVE: To compare changes in stress reactivity (measured via the biomarker salivary cortisol) and behavioral state in healthy newborn infants immediately following 1 of 2 interventions: (1) tactile-only stimulation or (2) a multisensory, auditory, tactile, visual, and vestibular stimulation with a control group. DESIGN: A randomized prospective design pilot study. SETTING: Normal newborn nurseries of 2 midwestern perinatal centers. PARTICIPANTS: Forty healthy newborn infants receiving standard nursing care. METHODS: Infants were randomly assigned to receive 15 minutes of tactile-only, auditory, tactile, visual, and vestibular, or no stimulation 30 minutes before feeding. Saliva samples were collected before, immediately following, and 10 minutes postintervention. Behavioral state was judged every minute. RESULTS: Tactile-only group infants had the largest increase in cortisol levels, followed by control group infants. In contrast, infants who received the multisensory intervention showed a significant steady decline in cortisol. Asleep was the predominant state for all 3 groups and cry was minimal. CONCLUSIONS: Tactile-only stimulation may increase infant stress reactivity while the benefit of the multisensory auditory, tactile, visual, and vestibular intervention may be in the reduction of infant stress reactivity. Interventions appeared to have minimal effect on stress reactivity based on behavioral state.

Concept clarification of neonatal neurobehavioural organization.

AIM: This paper is a report of a concept analysis of neonatal neurobehavioural organization for healthy full-term infants. BACKGROUND: The neonatal period is an opportune time for researchers and clinicians to assess and intervene for optimal neurobehavioural organization. Yet there is inconsistency and lack of clarity in a scientifically grounded definition of neonatal neurobehavioural organization. Clarification of the concept will strengthen research findings that influence practice for optimal infant development. METHOD: A concept analysis of the literature between 1939 and 2007 (n = 57) was conducted using Penrod and Hupcey's principle-based concept analysis and Morse's concept clarification. FINDINGS: The concept analysis within and across multiple disciplines revealed: (1) a view of the concept as a holistic phenomenon with multiple dimensions; (2) no agreement on the ideal instrument to operationally define the concept; and (3) consistency in implied meaning, but great variability in terminology. Neonatal neurobehavioural organization was defined as the ability of the neonate to use goal-directed states of consciousness, in reciprocal interaction with the caregiving environment, to facilitate the emergence of differentiating, hierarchical, and coordinated neurobehavioural systems, with ever-increasing resiliency and capacity to learn from complex stimuli. CONCLUSION: A clear conceptual definition will help the international community to communicate effectively within and between disciplines and to apply evidence-based research findings. It will encourage the development of valid and reliable instruments to capture the concept's multiple dimensions and direct attention to the infant's experience, which sculpts early neurobehavioural organization.

Quantitative ultrasound assessment of the rat cervix.

OBJECTIVE: The purpose of this research was to detect cervical ripening with a new quantitative ultrasound technique. METHODS: Cervices of 13 nonpregnant and 65 timed pregnant (days 15, 17, 19, 20, and 21 of pregnancy) Sprague Dawley rats were scanned ex vivo with a 70-MHz ultrasound transducer. Ultrasound scatterer property estimates (scatterer diameter [SD], acoustic concentration [AC], and scatterer strength factor [SSF]) from the cervices were quantified and then compared to hydroxyproline and water content. Insertion loss (attenuation) was measured in 3 rats in each of the 6 groups. Discriminant analysis was used to predict gestational age group (cervical ripening) from the ultrasound variables SD, SSF, and AC. RESULTS: Differences were observed between the groups (SD, AC, and SSF; P < .0001). Quantitative ultrasound measures changed as the cervix ripened: (1) SD increased from days 15 to 21; (2) AC decreased from days 15 to 21; and (3) SSF was the greatest in the nonpregnant group and the least in the day 21 group. Cervix hydroxyproline content increased as pregnancy progressed (P < .003) and correlated with group, SD, AC, and SSF (P < .001). Discriminant analysis of ultrasound variables predicted 56.4% of gestational group assignment (P < .001) and increased to 77% within 2 days of the predicted analysis. Cervix insertion loss was greatest for the nonpregnant group and least for the day 21 group. CONCLUSIONS: Quantitative ultrasound predicted cervical ripening in the rat cervix, but before use in humans, quantitative ultrasound will need to predict gestational age in the later days of gestation with more precision.

Sex differences in high-risk premature infants' asymmetric movement development.

High-risk premature infants are likely to show altered patterns in the development of reflexes and postural reactions. This study used the Modified-Measure of Behavioral Laterality (M-MOBL) neonatal assessment to explore differences in reflex and postural reactions among 26 male and female high-risk, premature infants born between 23 and 26 weeks gestational age. M-MOBL scores at 33-36.5 weeks were compared to those at 36.5-40 weeks of age, shortly before hospital discharge. The M-MOBL data were analyzed using the categorical method (CATMOD) repeated measures analysis of variance (ANOVAs) to compare the development of asymmetric movement patterns in: (1) non-injured and CNS-injured high-risk, premature infants, (2) control and experimental infants who received multi-sensory stimulation, and (3) males and female infants. Consistent with previously published reports of a right-(R) bias for healthy, full-term infant's movements, we found that high-risk premature females showed R-sided biases by 35-37 weeks post-conceptional age (PCA) for head turning responses and reflexes evoked by upper-body stimulation (i.e., palmar grasp, asymmetric tonic neck reflex (ATNR), incurvation). High-risk premature males however showed no significant difference in strength and coordination between the R-side and the left (L), as measured by the M-MOBL, in most of these upper-body movements tested at 35-37 weeks PCA. Neither premature males nor females showed asymmetries in foot and leg reflexes (placing, plantar grasp, Babinski). Healthy, full-term males did not show asymmetries in these reflexes either. However, full-term females showed an R-bias. With further research, the M-MOBL may become a useful instrument for early identification of infants with atypical CNS development who later exhibit atypical laterality patterns.

Feeding readiness in preterm infants: the relationship between preterm behavioral state and feeding readiness behaviors and efficiency during transition from gavage to oral feeding.

PURPOSE: The purpose of this secondary analysis was to assess whether alert behavioral states were associated with an increased number of feeding readiness behaviors (FRBs) and whether the number of FRBs were associated with subsequent feeding efficiency in healthy premature infants born between 29 to 35 weeks gestation. STUDY DESIGN AND METHODS: The data were collected as part of a larger study designed to compare the frequency of FRBs and feeding efficiency between control and experimental groups. Data from 21 stable premature infants were included in this secondary analysis. Infants were videotaped immediately prior to each of the first three oral feedings, from which infant behavioral state (IBS) and FRBs were assessed. Feeding efficiency was determined by calculating the ratio of feeding intake to feeding duration. RESULTS: IBS was not a significant predictor of the number of FRBs. The number of FRBs was predictive of feeding efficiency (p <.05). Group assignment was a marginally significant predictor of feeding efficiency (p < .10). Infant sex (p < .05), birthweight (p < .01), gestational age at birth (p <.01), and gestational age at entry (p < .05) were identified as significant predictors of the number of FRBs. Group assignment was marginally significant (p < .10). CLINICAL IMPLICATIONS: Feeding efficiency may be predicted by the increased number of FRBs immediately prior to feeding. An infant's attributes (sex, birth-weight, and gestational age) may relate to feeding efficiency and should be assessed when instituting oral feeding. Assessment of FRBs can be easily incorporated into routine clinical practice.

Developmental patterns of physiological response to a multisensory intervention in extremely premature and high-risk infants.

OBJECTIVE: To compare the developmental patterns of heart rate (HR), respiratory rate (RR), and hemoglobin oxygen saturation (SaO2) of premature infants with and without central nervous system (CNS) injury, and evaluate whether a multisensory intervention altered this development. SAMPLE: Thirty-seven premature infants born at 23-26 weeks with normal head ultrasounds or at 24-32 weeks and diagnosed with periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH) were studied at 33-35 weeks postconceptional age. DESIGN: Infants were randomly assigned to control and experimental groups. The experimental group infants received auditory, tactile, visual, and vestibular (ATVV) multisensory intervention twice daily from 33 weeks postconceptional age (PCA) until hospital discharge. MAIN OUTCOME MEASURES: HR, RR, and SaO2 were continuously monitored during baseline, intervention, and the 30-minute postintervention period. RESULTS: Between 33 and 35 weeks PCA, control group infants with and without CNS injury and experimental group infants without CNS injury had a significant decrease in resting mean HR, whereas RR and SaO2 remained stable. The infants with PVL who received the intervention showed increases in HR even at rest. CONCLUSIONS: The absence of a weekly decline in HR for experimental group infants with PVL suggests that PVL may affect maturation of the autonomic nervous system and increase risk of decelerative HR changes and associated clinical compromise. Infants diagnosed with PVL should be closely monitored during procedures or interventions that may be stressful or involve handling. Further research is needed to tailor multisensory interventions for infants with PVL.

Multisensory intervention improves physical growth and illness rates in Korean orphaned newborn infants.

The purpose of this study was to evaluate the effectiveness of a multisensory intervention on the physical growth and health of Korean orphaned infants. Fifty-eight full-term infants were randomly assigned to a control (n = 28) or an experimental (n = 30) group within 14 days postbirth. In addition to receiving the routine orphanage care, infants in the experimental group received 15 min of auditory (female voice), tactile (massage), and visual (eye-to-eye contact) stimulation twice a day, 5 days a week, for 4 weeks. Compared to the control group, the experimental group had gained significantly more weight and had larger increases in length and head circumference after the 4-week intervention period and at 6 months of age. In addition, the experimental group had significantly fewer illnesses and clinic visits. These data demonstrate that multisensory intervention in conjunction with human/social contact may be effective in facilitating growth for newborn infants placed in orphanages.

Effect of auditory, tactile, visual, and vestibular intervention on length of stay, alertness, and feeding progression in preterm infants.

This study determined whether an auditory, tactile, visual, and vestibular intervention (ATVV) reduced the length of hospitalization of 37 preterm infants by increasing the proportion of alert behavioral states, thereby improving their feeding progression. Participants comprised 12 infants born between 23 and 26 weeks' gestation with normal head ultrasounds and 25 CNS-injured infants born between 23 and 31 weeks' gestation. Infants were randomly assigned to the control group (11 males, five females) or study group (seven males, 14 females) at 32 weeks' postconceptional age. ATVV intervention was administered to the study group for 15 minutes, twice daily, 5 days per week, from 33 weeks of age until discharge. The study group demonstrated increased alertness during the first 5 minutes of intervention, which was significantly correlated to length of stay (p<0.05). The proportion of nippled (teat) intake increased significantly faster for the study group (p=0.0001). Infants in the study group were discharged at a mean of 36.54 weeks, 1.6 weeks earlier than control infants (p<0.05). ATVV intervention facilitated increased alertness, faster transition to complete nipple feeding, and decreased length of hospitalization.