published_or_final_version / Community Medicine / Master / Master of Philosophy

Most neonates and infants acquire HIV-1 infection as a result of mother-to-infant (vertical) transmission and are infected with the minor genotype with macrophage-tropic (R5) phenotype of the mother. Several studies suggest that infected infants have a higher viral load and develop AIDS more rapidly than infected adults, but the mechanisms of this differential HIV-1 infection are not known. The hypothesis of my dissertation is that viral determinants and differential cellular gene expression profiles influence differential HIV-1 replication and disease progression seen in neonates vs. adults. This work includes characterization of viral determinants, including reverse transcriptase (RT) and envelope gp120, and host determinants, including cellular transcription factors and cytokines that may be associated with differential HIV-1 replication in infants and adults. The characterization of HIV-1 RT gene from five mother-infant pairs following vertical transmission revealed a low degree of viral heterogeneity and a high conservation of intact open reading frames comprising functional domains and CTL epitopes. Biological characterization of HIV-1 subtype C envelope gp120 from infected patients from India was performed by constructing chimeras with HIV-1 subtype B. Infection of cell lines and primary cells with chimeric subtype C/B virus showed that the subtype C env gp120 from patients contributed to an increased rate of virus entry, which correlated with higher replication efficiencies and virus production in subtype C env chimeras compared with subtype B env chimeras and subtype B primary isolates. Higher level of viremia with subtype C infection compared with subtype B may be responsible for its rapid disease progression and spread. The mechanisms of HIV-1 replication in neonatal and adult cells was determined and found that differential HIV-1 replication in neonatal and adult cells is influenced at the level of HIV-1 gene expression. Evaluation of cellular gene expression profile of neonatal and adult mononuclear cells performed by microarray analysis identified several factors, including transcription factors, cytokines and matrix metalloproteinases that may be associated with increased HIV-1 gene expression and replication in neonates and infants. Taken together, these results provide new insights into the understanding of mecahnsims of HIV-1 vertical transmission, pathogenesis and disease progression in infected neonates and infants.

This research is part of an ongoing program, Nutrition Screening Tool for Every Preschooler (NutriSTEP®). NutriSTEP® is a valid and reliable 17-item, parent-administered, questionnaire for nutritional risk in preschoolers (3-5 years of age). Due to an expressed need across Canada, the specific objective of this research was to create a draft toddler (18-35 month) NutriSTEP®. Based on results from a comprehensive literature review, focus groups (n=6) with 48 parents of toddlers, and input from 13 pediatric nutrition experts, many questions from the original preschooler NutriSTEP® questionnaire were refined or removed, and novel questions were added. Basic changes included combining separate fruit and vegetable intake questions, and adding breast milk and formula as examples of dairy products. In conclusion, a 19 item Toddler NutriSTEP® was created to reflect the differences in nutritional risk between preschoolers and toddlers. Next steps in the development process include refinement, test-retest reliability and criterion validation. / Canadian Institutes of Health Research

Both intermittent oral gavage tube placement(0G) and indwelling nasogastric tube placement (NG) are acceptable methods for feeding preterm infants. A randomized controlled pilot study was conducted to examine the impact of OG versus NG placement on premature infant feeding transition. Twenty healthy premature infants were enrolled and thirteen completed the study. The results were not statistically significant. Age at last tube feed averaged 35 weeks gestational age (GA) for the intermittent group and 35+4 weeks GA for the indwelling group (p=0.181). Infants in both groups were discharged at an average of 36 weeks GA (p=.836) and averaged suckled volumes at 35 weeks GA was 134.4cc/kg/day for the intermittent group versus 111.8cc/kg/day for the indwelling group (p=0.240). Infant feeding patterns were analyzed descriptively and found to be consistently variable. The lack of consistency in feeding development has implications for feeding plan development and feeding transition care.

Background: Unmitigated immunization pain in infants has the potential to impact long-term health outcomes. Teaching parents in the prenatal period may increase utilization of pain management (PM) strategies in clinical practice. Objective: To assess the efficaciousness of teaching parents in the prenatal environment and its impact on the number of analgesic PM strategies utilized during the 2-month immunization appointment. Methods: This partially blinded cluster randomized controlled trial enrolled mothers from prenatal classes at Mount Sinai Hospital. Classes were randomized to receive a presentation on either immunization PM or general immunization information. Results: One hundred and ninety-seven mothers from 28 classes participated in this study. There was a statistically significant increase (p<0.01) in the use of one or more analgesic interventions in the group that received a presentation on immunization PM compared to those who received general immunization information. Conclusions: Prenatal classes are a suitable environment to educate parents about immunization PM.

Background: Unmitigated immunization pain in infants has the potential to impact long-term health outcomes. Teaching parents in the prenatal period may increase utilization of pain management (PM) strategies in clinical practice. Objective: To assess the efficaciousness of teaching parents in the prenatal environment and its impact on the number of analgesic PM strategies utilized during the 2-month immunization appointment. Methods: This partially blinded cluster randomized controlled trial enrolled mothers from prenatal classes at Mount Sinai Hospital. Classes were randomized to receive a presentation on either immunization PM or general immunization information. Results: One hundred and ninety-seven mothers from 28 classes participated in this study. There was a statistically significant increase (p<0.01) in the use of one or more analgesic interventions in the group that received a presentation on immunization PM compared to those who received general immunization information. Conclusions: Prenatal classes are a suitable environment to educate parents about immunization PM.

Introduction. There is clear evidence that children raised in families affected by parental drug use are at high risk for a wide range of adverse outcomes, including; early cognitive and language delay (van Baar & de Graaff, 1994); poor school attendance and educational under-achievement (Hogan & Higgins, 2001; Steinhausen, Blattmann, & Pfund, 2007); substance abuse and psychological problems (Keller, Catalano, Haggerty, & Fleming, 2002; Kilpatrick, Acierno, Saunders, Resnick, Best, & Schnurr, 2000; Kolar, 1994; Lagasse, Hammond, Liu, Lester, Shankaran, Bada et al., 2006; Merikangas, Dierker, & Szatmari, 1998; Moss, Vanyukov, Majumder, Kirisci, & Tarter, 1995; Nunes, Weissman, Goldstein, McAvay, Beckford, Seracini et al., 2000; Nunes, Weissman, Goldstein, McAvay, Seracini, Verdeli et al., 1998; Stanger, Higgins, Bickel, Elk, Grabowski, Schmitz et al., 1999). Careful examination of the impact of parental drug use on children and the developmental mechanisms associated with risk and resilience is central to the establishment of appropriate intervention. Children born to mothers who are drug dependent and enrolled in methadone maintenance treatment during pregnancy face the “double jeopardy” of prenatal drug exposure and post-natal environmental disadvantage (Zuckerman & Brown, 1993). This research aimed to identify early developmental difficulties or differences in communicative and cognitive development, and in particular the joint attention skills, of young children born to mothers engaged in methadone maintenance treatment. Of particular interest was the way in which pre- and postnatal factors combined to influence developmental outcome at age 2 years. This prospective, longitudinal study offered the opportunity to indentify early indicators of developmental differences in this group and thus, contribute to a better understanding of the long-term mechanisms of risk. Research Methods. Sixty children born to mothers engaged in methadone maintenance treatment and 60 randomly-selected, non-exposed comparison children were followed prospectively from birth to age 2 years. During the third trimester of pregnancy, mothers completed a comprehensive maternal interview. At 18 months, children were visited at home and evaluations of the social background, family and childrearing context were completed. At age 2 years, all children underwent a developmental assessment that included the Early Social Communication Scales (ESCS) (Mundy, Hogan, & Doehring, 1996). The ESCS consists of a semi-structured series of activities, which assess the joint attention abilities, social skills and interactive behaviour of infants aged 8 to 30 months. The focus of this study was on children’s use of two types of communicative behaviour – requesting and affect-sharing communications. Alongside the ESCS, the Mental Development Index (MDI) and language items from the Bayley Scales of Infant Development (BSID-II) (Bayley, 1993) and the Communication and Symbolic Behaviour Scales– Developmental Profile (CSBS-DP) (Wetherby & Prizant, 1998), were used to assess concurrent cognitive and language skills. Results. The results of this study indicated that children born to mothers engaged in methadone maintenance treatment were typically growing up in single-parent families (p=<.0001) and in welfare-dependent households (p=<.0001). Methadone-exposed children were also more likely to be living in out-of-home care placements at age 18months than comparison group children (p=<.0001). Their caregivers were less likely to be accepting of (p=<.01) and responsive to their needs (p=.008) compared to parents of comparison children. At home, methadone-exposed children had fewer learning opportunities (p=<.0001) and were more likely to live in houses where the television was on for longer, compared to non-exposed children (p=<.001). Caregivers of methadone-exposed toddlers reported more depression (p=<.0001), more illicit substance use (p=<.0001) and more family stress (p=.004) than comparison caregivers. They were also more often victims of psychological aggression (p=.002) and violence from others (p=<.0001), but they also reported that they were more likely to use psychological aggression (p=<.001) and physical punishment (p=<.03) in managing their children’s behaviour than comparison caregivers. The developmental assessment at age 2 years suggested that methadone-exposed children were significantly more likely to engage in communicative behaviour, which expressed a request, than non-exposed, comparison children (p=.03). On the other hand, analysis suggested that whilst methadone-exposed children were less likely than comparison children to engage in communication, which had the goal of affect sharing, this difference did not reach significance (p=.27). Previous research links greater use of requesting behaviours with later behaviour problems (Sheinkopf, Mundy, Claussen, & Willoughby, 2004). The MDI, BSID language measure and CSBS results further indicated significant delay in both cognitive (p =<.0001) and language development (p =<.0001) in the methadone-exposed group, compared to the comparison group. Between group differences were attenuated by control for confounding social background and prenatal factors, including maternal education, gestational age, other drug exposures during pregnancy and gender, but significant differences remained. Further analysis suggested that parenting practices and family environment factors were important intervening influences on the relationship between being born to a mother engaged in methadone maintenance treatment and poorer outcomes. More specifically, the association between methadone-exposure and differences in joint attention behaviours, were explained by caregiver use of psychological aggression (p=.01), caregiver disruption (p=.07) and caregiver stress (p=.01). On the other hand, poorer cognitive and language outcomes were explained by family contextual factors, including a less child-centered home environment (p=.008), caregiver disruption (p=.001), increased use of background TV (p=.02) and fewer stimulating activities (p=.06) Discussion. The family circumstances of children born to mothers engaged in methadone maintenance treatment during pregnancy, when compared with a group of randomly-selected comparison children, showed pervasive differences and multiple disadvantage. Findings suggest that these differences in family disruption, family functioning and parenting practices explain the negative outcomes of methadone-exposed children in early cognitive and communication skills at age 2 years. These results raise concerns for the later functioning of methadone-exposed children and emphasise the key importance of early intervention for children and families affected by parental drug use.

Little literature currently exists on naps in infancy, particularly in Early Childhood Education (ECE) settings. This study follows previous research by Stuart (2011) on children attending ECE Centres. The objective of the current study was to examine the architecture of naps in infants who were transitioning to attendance at an ECE Centre. Four males and one female aged between 4 and 11 months contributed to five case studies. Digital video recordings were made of participants napping in two settings: the home and the ECE Centre. Baseline recordings were made in the home only, and recordings were made in both settings as infants transitioned to the ECE Centre, and once they were deemed to be “settled” at the centre. The recordings were then coded to determine sleep states and amount of caregiver interaction. The results showed that all infants displayed a reaction to the transition to ECE attendance. However, the transition to the ECE Centre had a minimal effect on most infants’ home naps. Overall, naps were longer and more efficient at home than at the ECE Centre, and infants engaged in more Active Sleep than Quiet Sleep in both settings. Caregiver interaction during naps also differed between the settings. This is an important area of study as attendance at ECE Centres in New Zealand is increasing (Ministry of Education, 2011b), and as such, suggestions for future research have been made.

When a woman discovers that she is pregnant, she begins a process of internal work to develop her mother role. This process has been outlined in the literature for the delivery of a healthy full-term baby, however little is known about the process for mothers of medically fragile babies. A threatened pregnancy and subsequent delivery of a medically fragile baby involves a different process of internal work by the mother to prepare for her role. Mothers with a baby in the Neonatal Intensive Care Unit (NICU) experience stress, uncertainty, and anxiety potentially causing a permanent impact on the successful development of her role. It is the purpose of this dissertation to explore the process of mother role development among those first-time mothers having a baby in the NICU. This study was conducted using a qualitative grounded theory method. Data collection consisted of personal journals, in-person interviews, researcher notes and observation. The specific aims include (1) describing the disruption in the individual’s preconceived idea of being a mother, (2) exploring specific strategies that support the mother in the development of her role while in the NICU, (3) describing the mother’s perception of her role during physiologic changes in her baby, (4) examining the mother’s evaluation of her mother-role success, (5) developing a deeper understanding of the process of developing the role of mother while in the NICU, and (6) constructing a theoretical model to illustrate the process of becoming a mother while in the NICU.

The purposes of this study were to describe the attitudes of parents toward parenting and infant learning and to determine the effect of a parenting program on those attitudes.Subjects of the study consisted of fifty-five mothers and fathers. There were thirty-one mothers and twenty-four fathers. The sample included all males and females with their infants who enrolled in six parent-infant classes. Sessions, each lasting sixty minutes, were held once a week from December 1976 through February 1977. No data was gathered on the infants in the program. There were six classes used in the study. One of the six was taught by the researcher as a pilot class from September 1976 through November 1976. A pretest was administered in the first session of every class and the same test was given in the last session of every class.One instrument was employed in the study. The Personal Reaction Scale was chosen as a measuring instrument to gather data on attitudes of subjects in the study. It was specifically designed by the researcher for the study as adapted from Osgood's Semantic Differential.Five null hypotheses were tested in the study:1) there will be no statistically significant difference in the attitudes of mothers with respect to each of twelve stimulus statements and the attitudes of fathers with respect to the same twelve stimulus statements, as recorded by the Personal Reaction Scale, 2) there will be no statistically significant difference in the attitudes of parents of one child with respect to each of twelve stimulus statements and the attitudes of parents of more than one child with respect to the same stimulus statements, as recorded by the test instrument, 3) there will be no statistically significant difference in the attitudes of parents 25 years-of-age and younger with respect to twelve stimulus statements and the attitudes of parents 26 years-of-age and older with respect to the same twelve statements, 4) there will be no statistically significant difference in the attitudes of parents who report reading one article or book with respect to twelve stimulus statements and the attitudes of parents who report reading more than one article or book with respect to the same twelve statements, 5) there will be no statistically significant difference in the attitudes of parents on a pretest with respect to twelve stimulus statements and parents on a posttest after completion of an educational program with respect to the same statements, as recorded on the test instrument.A null hypothesis of no difference between the mean vectors of the groups was rejected if the computed statistics, the F ratio from a multivariate analysis exceeded the appropriate tabled value for the .05 level of confidence.A statistically significant difference was not found to exist between mothers' and fathers' attitudes, between those parents' attitudes with one child and those with more than one child, between the attitudes of parents 26 years-of-age and older and parents 25 years-of-age and younger, and between parents who reported reading one book or article on parenting or infant learning and parents who reported reading more than one book or article. A statistically significant difference was found to exist between the attitudes of parents at the beginning of the parent educational program and the parents' attitudes at the completion of the program.The following inferences may he drawn from this study and from related research the implied behavior need aid parents in determining child rearing practices, 2) the roles of parents are important in the development of the young child and attitudes are important determinants of parental behavior in development of parenting patterns.