College of Nursing Premature Infants & Their Development to Adulthood

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1 College of Nursing Premature Infants & Their Development to Adulthood Mary C. Sullivan, PhD, RN, FAAN Professor, University of Rhode Island, College of Nursing RI Nursing Educa;on Center 350 Eddy Street Providence, RI

College of Nursing When you re a nurse you know that every day you will touch a life or a life will touch yours Premature Infants & Their Development to Adulthood Mary C.

before 37 weeks gestation 70% of premature infants spend time in neonatal intensive care (NICU) (Holsti et al.

the US, 15 million worldwide (NCHS 2014; WHO 2016) v Annual cost ~ $26 billion (Behrman & Stith Butler 2007) v Preterm infants are at risk - especially when prematurity is coupled with neonatal

2 College of Nursing When you re a nurse you know that every day you will touch a life or a life will touch yours Premature Infants & Their Development to Adulthood Mary C. Sullivan, PhD, RN, FAAN Our gra'tude to the Par'cipants & Families NIH NICHD 19195; NIH NINR R01 NR Background Most intense experiences of adversity for infants is premature birth delivery before 37 weeks gestation 70% of premature infants spend time in neonatal intensive care (NICU) (Holsti et al.,2005; MOD 2011) Multiple jeopardy: immature body/organ system + NICU environment + medical/neuro illness + maternal separation Scope v Each year 1 in 10 babies are premature; >450,000 per year in the US, 15 million worldwide (NCHS 2014; WHO 2016) v Annual cost ~ $26 billion (Behrman & Stith Butler 2007) v Preterm infants are at risk - especially when prematurity is coupled with neonatal illness (Anderson, 2014; Saigal, 2014; Breeman et al., 2017). v Poorer physical & mental health, lower cognition, academic, social, behavioral problems (e.g., Taylor 2017; Wolke 2016; Saigal et al., 2016) v New problems can emerge at later ages Purpose of Longitudinal Study 1. Examine developmental outcome of premature infants categorized by neonatal illness 2. Understand and predict outcomes using theoretical models that incorporated environmental context. 3. Understand the effects of neonatal morbidity, environmental context, and cumulative effects on salient developmental outcomes. 1

3 Objectives 1. Describe a nursing research program on the developmental outcomes of premature infants led by nurse scientists 2. Explain the theoretical perspective of Developmental Origins of Health & Disease 3. List 2 research findings from the longitudinal study of premature infants Theoretical Framework Cumulative Risk Medical Risk Environmental Risk {birth, 1m, 18m, 30m, 4y, 8y, 12y, 17y} Cumulative Protection Family Protect Individual Protect {18m, 30m, 4y, 8y, 12y, 17} Trajectories Birth Age 4 Age 8 Age 12 Age 17 Developmental Outcomes Sample at Birth Prospec've, longitudinal 5-group design N=215 recruited at birth and followed in 9 waves to age 23y Infancy Birth, 1m, 3m, 9m, 18m, 30m N = 215 PRETERM GROUPS (<37 weeks gesta<on) Preterm Groups Full Term Infants Healthy Preterm Medical Preterm Neurological Preterm Small for Gesta<onal Age Neonatal Criteria Full Term; medically & neurologically healthy no medical/neurological complica<ons neonatal medical illness (BPD, RDS, NEC, sepsis) neonatal neurological illness (Grade III & IV IVH, meningi<s, shunted hydrocephalus) birth weight for gesta<onal age < 10 th percen<le Recruitment Physiology/cry acoustics Motor Skills Neurobehavior (NBAS) Risk Biological, Environmental Protect Maternal, Family Home Visit HOME environment Preschool Study Age 4 N = 184 School Age Study Age 8 N = 191 Motor Skills Visual-Motor Integration Socioemotional Competence Mastery, Problem Solving Home Visit HOME environment Cognition Language Skills Risk Biological, Environmental Protect Maternal, Family Motor Skills Problem Behaviors Socioemotional Competence, Home Visit Risk Biological, Environmental Protect Maternal, Family HOME environment Visual-Perceptual Skills Social Skills School Visit Cognition Academic Achievement School Record Review Peer Observation Teacher Questionnaires 2

4 Early Adolescent Study Age 12 N = 186 Late Adolescent Study Age 17 N = 180 Motor Skills Problem Behaviors Home Visit HOME environment Visual-Perceptual Skills Social Skills Socioemotional Competence Risk Peer Interaction Biological, Environmental Protect Maternal, Family School Visit School Record Review Teacher Questionnaires Functional Performance Executive Function Cognition School Visit School Record Review Academic Achievement Risk Problem Behaviors Biological, Environmental Risky Behaviors Social Skills Protect Maternal, Family Theoretical Framework Developmental Origins Theory of Health & Disease BIRTH AGE 23 ADULT OUTCOMES FETAL PROGRAMMING Prematurity Neonatal stress Sullivan et al., 2008 HPA DYSREGULATION ALLOSTATIC LOAD Cumulative Risk Biological Environmental Cumulative Protect Family Individual HEALTH CARDIOVASCULAR FUNCTION FUNCTIONAL PERFORMANCE EMOTIONAL INTELLIGENCE EXECUTIVE FUNCTION WORK COMPETENCE Home Visit Blood Glucose, Lipids Diurnal Cortisol & saa Health Behaviors Health Related Quality of Life Work Competence Emotional Intelligence Diet Preterm Infant to Adult Study Age 23 N = 180 Executive Function Heart Center Visit Cardiac Function Pulmonary Function Functional Performance Risk Problem Behaviors Biological, Environme Risk Taking Behaviors Protect Maternal, Fa Self Cortisol & Salivary Alpha-Amylase Stress Reactivity RESULTS Longitudinal Sample Retention Birth N=215 Age 4 N=184 Age 8 N=191 Age 12 N=186 Age 17 N=180 Age 23 N=180 89% 99% 98% 97% 99% 88% 87% 85% 85% 3

No group differences on HS graduation rates 50% had Post Secondary educa'on vocational

school 1.8% 5 levels of SES equally distributed within each neonatal group.

years [χ²(4,167)=3.71, p=.45] Occupation [χ²(12,169)=15.41, p=.

technician,semiprofessional 14% management, administrative, executive 23% students 31%

5 Sample at Age 23 Years (M=23.2, SD =1.0) Young Adult Educa<on 92% completed high school (n = 152) NS, but wide variability No group differences on HS graduation rates 50% had Post Secondary educa'on vocational 6%, community college 4%, college 38%, (Neuro PT had lowest completion) graduate school 1.8% 5 levels of SES equally distributed within each neonatal group. Young Adult Employment & Occupa<on Young Adult Financial Support 69% employed at 23 years [χ²(4,167)=3.71, p=.45] Occupation [χ²(12,169)=15.41, p=.22] 36% unskilled, semiskilled occupations 27% skilled, sales/clerical, technician,semiprofessional 14% management, administrative, executive 23% students 31% unemployed Financial Support [χ²(16,169)=17.74, p=.34] 66% self 24% par'al parents 5% spouse 4% disability, workers compensa'on Males have CVD risk at 23 years Females have CVD risk at 23 years 4

-0.507-0.261 0.449-0.191 0.639 Hobel -0.944 LOS BW 0.854 0.929 GA -0.947 med1mo 0.823 NEC 0.254 BPD 0.543 O2dur 0.911 neuro1mo 0.970 IVH shunt 0.307 0.

752 neuro4 neuro8 0.725 neuro12 0.875 neuro17 med4 med8 med12 med17 0.668 0.568 0.419 0.413 0.592 0.642 Birth (Factor 1) Toddler (Factor 2) 0.479 0.

Awakening 2. 45 minutes after awakening 3. 4 hours after awakening 4. 8 hours after awakening 5.

10 HPT & SGA groups: sharp increase in cortisol after awakening & sharp decline throughout the day 0.05 MPT & NPT groups: illustrate blunted 0.

high cortisol concentration in morning, gradual decline throughout the day Full Term Heathly PT Medical PT Neuro PT SGA PT Prematurity, Birth Weight,

6 Hobel LOS BW GA med1mo NEC BPD O2dur neuro1mo IVH shunt General (Birth) Neuro (Birth) neuro neuro med med neuro4 neuro neuro neuro17 med4 med8 med12 med Birth (Factor 1) Toddler (Factor 2) Child/Adolescent (Factor 3) Medical Index 3/17/18 Diurnal Cortisol Sampling at 23 Years l 5 samples collected during typical day: 1. Awakening minutes after awakening 3. 4 hours after awakening 4. 8 hours after awakening 5. Bedtime Mean Raw Units of Cor<sol (ug/dl) Diurnal Cortisol Pattern by Preterm Group HPT & SGA groups: sharp increase in cortisol after awakening & sharp decline throughout the day 0.05 MPT & NPT groups: illustrate blunted 0.00 response in diurnal cortisol pattern Awake 45 min 4 hours 8 hours Bed<me Time of Diurnal Cor<sol Collec<on FT group: normal diurnal pattern, with high cortisol concentration in morning, gradual decline throughout the day Full Term Heathly PT Medical PT Neuro PT SGA PT Prematurity, Birth Weight, SES Influence Cortisol Figures 1a-1d Significant Interaction of preterm group, birth weight, & SES F(4,504).3.51, p<.01, Cumulative Medical Risk Index: Birth to Age 17 Years X 2 =.246, df=1, p=.62; RMSEA=0.000, 90% CI = , NFI=.997 5

Cumulative Protection Index from Birth to Age 12 Years hometotbirth 0.796-0.336 hometot4 0.747 hometot8 0.825 Protect Factor 1 hometot12 0.760 0.892 poahtot12 0.570 poch8tot 0.

7 Cumulative Protection Index from Birth to Age 12 Years hometotbirth hometot hometot Protect Factor 1 hometot poahtot poch8tot Protect Factor 2 chs Protection Index poihstot msetot mc Protect Factor 3 mc msritot inv mcs teach Protect Factor 4 mcs X 2 =.588, df=1, p=.44 RMSEA=0.000, 90% CI = NFI=.996 qualtot mcs Winchester, S. B., Sullivan, M.C., Roberts, M.B., Bryce, C.I., & Granger, D. (Prepublished July 24, 2017). Longterm effects of prematurity, cumulative medical risk, and proximal and distal social forces on individual differences in diurnal cortisol at young adulthood. Biological Research for Nursing. DOI: / Revisit the Objectives. ü Describe a nursing research program on the developmental outcomes of premature infants led by nurse scientists ü Explain the theoretical perspective of Developmental Origins of Health & Disease ü List 2 research findings from the longitudinal study of premature infants F (5, 553). 2.31, p =.04 SUMMARY of 23 Year Outcomes ² Wide variability in education, employment, occupation at age 23 years ² Similar to FT, but slightly lower ² Not reaching markers of independent living ² More health problems than FT ² Health, including diet not optimal; early risk for CVD SUMMARY Cortisol at 23 Years Dis'nct payerns for full term and preterm groups, in par'cular, preterm groups with neonatal illness. Blunted diurnal cor'sol payerns were observed for the MPT and NPT groups Birth weight was an important contributor to diurnal cor'sol payern at age 23. SES and Protec've factors affect cor'sol rhythm 6

CONCLUSIONS Findings support HPA axis as mechanisms underlying the Developmental Origins Theory. Developmental Origins framework Ø a mechanism underlying fetal origins of adult chronic disease.

8 CONCLUSIONS Findings support HPA axis as mechanisms underlying the Developmental Origins Theory. Developmental Origins framework Ø a mechanism underlying fetal origins of adult chronic disease. Ø has impact on metabolic and stress response programming which effects long term physical and behavioral health. Ø offers a lifespan perspec've on preterm birth and adult outcomes, with poten'al for early iden'fica'on of those at risk for later stress-related disease. IMPLICATIONS Longitudinal follow-up of premature infants and the stress response system, such as the HPA axis, suggests a greater understanding of the role of this stress-related biomarker in adulthood. Con'nued health monitoring of prematurely born infants is important as they have higher risk for adult illness. Roles for neonatal nurses include monitoring the physiological stability of preterm infants, careful assessment of stress behaviors, and collabora've decision making for interven'ons. The ul'mate reason to understand the e'ology of long-term outcomes is iden'fica'on of possibili'es for preventa've interven'ons. Our Gratitude - to the Par'cipants & Families Funding NIH NICHD 19195; NIH NINR R01 NR Institutions University of Rhode Island, College of Nursing, Kingston, Rhode Island Women & Infants Hospital, Brown Center for Children, Providence, Rhode Island InsLtute for Interdisciplinary Salivary Bioscience Research, Arizona State University, Arizona State University, Tempe, AZ University of Chicago, Pritzker School of Medicine/Comer & Larabida Children s Hospital Baby Talk: Unlocking the Secrets of the Infant Brain RI PBS on youtube hyps:// Thanks to the Team Project Director: Suzy Winchester Barry Lester, Margaret McGrath Co-investigators: William Oh, Betty Vohr, Ron Seifer, Michael Msall, Doug Granger, Biostatisticians: Mark Pueker, David Ahern, Steve Farrone, Mary Roberts Research Assistants: Bernai Manna, Christine Andrade, Kelli Rocherolle, Jennifer Verrill, Marni Gonzales, Courtney Clark, Allison Hitte, April Duffy. Erin Hunt, Sarah Inlow, Doreene Carr, Karen Murphy, Lea Lockwood, Laura Moon, Tom Doyle, Manuela Barcelos, Jennifer DePalma, Melissa MacNeill, Ryan Sawyer, Erica Oliviera, Matt Straub, Jennifer DePalma CON Graduate Assistants: Katheleen Hawes, Linda Sacco, Irene Lang, Jane Gallagher, Christina Poore, Maribeth Welesko Research Nurses: Francine Brem, Nicole Smith, Sherry Matook, Jo Ann Stengel, Heather Comerford, Robin Miller 7

9 Publications from the RI Premature Infant Cohort Mary Sullivan University of Rhode Island, College of Nursing Providence, RI Book chapters Lester, B.M., McGrath, M.M., Garcia-Coll, C.T., Brem, F.S., Sullivan, M.C., & Mattis, S.B. (1994). Relationship between risk and protective factors, developmental outcome and the home environment at 4-years of age in term and preterm infants. In H. Fitzgerald (Ed.), Children in Poverty: Research, Health Care, and Policy (pp ). New York: Garland Press. McGrath, M.M., Lester, B.M., Boukydis, C.F.Z., & Sullivan, M.C. (1994). Predicted validity of repeated Neonatal Behavioral Assessment Scale (NBAS) Exams in 4-year-old term and preterm infants. In C. Garcia-Coll (Chair), Arousal and self regulation in preterm and full term infants. Infant Behavioral & Development: Special ICIS Issue (Vol. 9). Norwood, NY: Ablex Publishing Corp. Msall, M. E., Sullivan, M., Park, J. (2010). Pathways of risk and resiliency after prematurity: Role of socioeconomic status. In C. Nosarti, R. Murray, M. Hack (Eds). Neurodevelopmental outcomes of preterm birth: from childhood to adult life. New York: Cambridge University Press. PMCID # NIHMSID # Winchester, S. B., Sullivan, M. C., & Msall, M. E. (2014). Executive function in infants born preterm with varying birth weights and morbidities at emerging adulthood. In K. P. Bennett (Ed.), Executive functioning: Role in early learning processes, impairments in neurological disorders and impact of cognitive behavior therapy (CBT) (pp ). Hauppauge, NY: Nova Science Publishers. Msall, M.E., Sobatka, S.A., Dmowska, A., Hogan, D. & Sullivan, M. (2018). Life course health development outcomes after prematurity: Developing a community, clinical, and translational research agenda to optimize health, behavior, and functioning. In Halfon, N., Forrest, R.M., Lerner, R.M., & Faustman, E.M. (Eds). Handbook of Life Course Health Development (pp ). Open Access: Springer. DOI / _14. Peer-reviewed Publications Lester, B.M. Developmental outcome prediction from acoustic cry analysis in term and preterm infants. Pediatrics, 80(4), , Rapisardi, G., Vohr, B., Cashore, W., Peucker, M., & Lester, B.M. Assessment of infant cry variability in high risk infants. Journal of Pediatric Otorhinolaryngology, 17, , Lester, B.M., Boukydis, C.F.Z., Garcia-Coll, C.T., Hole, W., & Peucker, M. Infantile colic: Acoustic cry characteristics, maternal perception of cry, and temperament. Infant Behavior and Development, 15, 15-26, McGrath, M.M., Lester, B.M., & Boukydis, C.F.Z. Determinants of maternal self-esteem in the neonatal period. Infant Mental Health Journal, 14(1), 35-48, Meyer, E.C., Zeanah, C.H., Boukydis, C.F.Z., & Lester, B.M. A clinical interview for parents of high-risk infants: Concept and applications. Infant Mental Health Journal, 14(3), , Lester, B.M., Boukydis, C.F.Z., Garcia-Coll, C.T., Peucker, M., McGrath, M.M., Vohr, B.R., Brem, F., & Oh, W. Developmental outcome as a function of the goodness of fit between the infant's cry characteristics and the mother's perception of her infant's cry. Pediatrics, 95(4), , Lester, B.M., Boukydis, C.F.Z., & LaGasse, L. Cardiorespiratory reactivity during the Brazelton Scale in term and preterm infants. Journal of Pediatric Psychology, 21(6), , Boukydis, C.F.Z. & Lester, B.M. Infant crying, risk status and social support in families of preterm and term infants. Early Development and Parenting, 7, 31-39, Bigsby, R., Coster, W., Lester, B.M., & Peucker, M.R. Motor behavioral cues of term and preterm infants at 3 months. Infant Behavior and Development, 19, , McGrath, M.M., Sullivan, M.C., Brem, F., & Coduri-Rocherolle, K. (1995). Mastery motivation and cognitive development in 4-year-old term and preterm children. Journal of Pediatric Nursing, 10 (5), McGrath, M.M., & Sullivan, M.C. (1998). Maternal interaction patterns and preschool outcomes in high-risk children. Nursing Research, 47(6), McGrath, M.M. (1997). Estimating risk indexes and protective factors in high risk children. Clinical

10 Effectiveness in Nursing, 1, Sullivan, M.C., & McGrath, M.M. (1999). Proximal and distal correlates of maternal control style. Western Journal of Nursing Research, 21(3), McGrath, M.M., & Sullivan, M.C. (1999). Medical and Ecological Factors in Estimating Motor Outcomes of Preschool children. Research in Nursing and Health, 22, McGrath, M. M., Sullivan, M. C., Lester, B. M., & Oh, W. (2000). Longitudinal follow-up study of very low birth weight infants with various neonatal morbidities. Pediatrics, 106(6), McGrath, M.M.& Sullivan, M. C. (2002). Birthweight, neonatal morbidities, and school age outcomes in full term and preterm infants. Issues in Comprehensive Pediatric Nursing, 25(4), Sullivan, M. C. & McGrath, M. M. (2003). Perinatal morbidity, mild motor delay, and later school outcomes. Developmental Medicine & Child Neurology, 45, McGrath, M.M. & Sullivan, M. C. (2003). Testing proximal and distal protective processes in preterm high risk Children. Issues in Comprehensive Pediatric Nursing. 26, Leffers, J.M., Martins, D.C., McGrath, M.M., Brown, D.G., Mercer, J., Sullivan, M.C., Viau, P. (2004). Development of a theoretical construct for risk and vulnerability from six empirical studies. Research and Theory for Nursing Practice: An International Journal, 18: (1), McGrath, M.M., Sullivan, M.C., Devin, J., Fontes-Murphy, M., Barcelos, S., DePalma, J., Faraone, S. (2005). Early precursors of low attention and hyperactivity in a preterm sample at age four. Issues in Comprehensive Pediatric Nursing, 28, Sullivan, M.C. & Msall, M.E. (2007). Functional performance in preterm children at age 4.Journal of Pediatric Nursing, 22 (4), doi: /j.pedn PMCID: PMC NIHMSID: NIHMS Sullivan, M.C. & Hawes, K. (2007). A decade comparison of preterm motor performance at age 4. Research in Nursing and Health, 30, Sullivan, M.C., Hawes, K., Barcelos Winchester, S., & Miller, R.J. (2008). Developmental origins theory: Prematurity to adult disease. Journal of Obstetric, Gynecologic & Neonatal Nursing, 37, doi: /j x PMCID: PMC NIHMSID: NIHMS Sullivan, M.C., McGrath, M.M., Hawes, K., & Lester, B.M. (2008). Growth trajectories of preterm infants: Birth to 12 years. Journal of Pediatric Health Care, 22, doi: /j.pedhc NIHMSID # Miller, R.J., Sullivan, M. C., Hawes, K., & Marks, A. K. (2009). The effects of perinatal morbidity and environmental factors on health status of preterm children at age 12. Journal of Pediatric Nursing, 24(2), doi: /j.pedn NIHMS Barcelos Winchester, S., Sullivan, M.C., Marks, A.K., Doyle, T., DePalma, J., & McGrath, M. (2009). The effects of risk and protective processes at age 12 on school performance of preterm infants. Western Journal of Nursing Research, 31(7), doi: / PMCID # NIHMSID # Sullivan, M.C., Mitchell, P.A., Miller, R. J., Winchester, S. B., & Ziegler, J. W. (2011, September). Cardiopulmonary outcomes in young adults born prematurely with varying birth weights. Pediatric Work Physiology conference, University of Exeter, England. Sullivan, M. C., Msall, M. E., & Miller, R. J. (2012). 17-Year outcome of preterm infants with diverse neonatal morbidities: Part 1, Impact on physical, neurological, and psychological health status. Journal for Specialists in Pediatric Nursing, 17, doi: /j x NIHMS# Sullivan, M. C., Miller, R.J. & Msall, M. E. (2012). 17-Year outcome of preterm infants with diverse neonatal morbidities: Part 2, Impact on activities & participation. Journal for Specialists in Pediatric Nursing, 17, doi: /j x NIHMS Sullivan, M. C., Winchester, S.B., Parker, J. G, & Marks, A. K. (2012). Characteristic processes of close peer friendships of preterm infants at age 12. Scientifica, 2012, Article Retrieved from NIHMS Winchester, S. B., Sullivan, M.C., Roberts, M.B., & Granger, D. (2016). Prematurity, birth weight, and socioeconomic status are linked to atypical diurnal hypothalamic-pituitary-adrenal axis activity in young adults. Research in Nursing and Health, 39, DOI: /nur Sharafi, M., Duffy, V, B., Miller, R. J., Winchester, S. B., Heudo-Medina, T., & Sullivan, M. C. (2016). Dietary behaviors of adult born prematurely may explain future risk of cardiovascular disease. Appetite, 99, doi.org/ /j.appet Scott, A., Winchester, S. B., & Sullivan, M. C. (2017). Trajectories of problem behaviors from 4 to 23 years in

11 former preterm infants. International Journal of Behavioral Development. Online First January 1, DOI: / Roberts MB, Sullivan MC, Winchester, S.B. (2017). Examining solutions to missing data in longitudinal nursing research. Journal for Specialists in Pediatric Nursing, 22:e doi /jspn Sullivan, M.C., Winchester, S.B., Bryce, C.I., & Granger, D.A. (2017). Prematurity and perinatal adversity effects hypothalamic-pituitary-adrenal axis reactivity to social evaluative threat in adulthood. Developmental Psychobiology, 59: DOI: /dev Winchester, S. B., Sullivan, M.C., Roberts, M.B., Bryce, C.I., & Granger, D. (2018). Long-term effects of prematurity, cumulative medical risk, and proximal and distal social forces on individual differences in diurnal cortisol at young adulthood. Biological Research for Nursing. 20 (1), DOI: / Troutman, J.A., Sullivan, M.C., Carr, G.J., Fisher, J. (Early View, March 13, 2018). Development of growth equations from longitudinal studies of body weight and height in the term and preterm neonate: From birth to four years postnatal age. Birth Defects Research Part B: Developmental and Reproductive Toxicology. DOI: /bdr2.1214

CURRICULUM VITAE Mary Cunningham Sullivan

CURRICULUM VITAE Mary Cunningham Sullivan Women & Infants Hospital Brown Center for the Study of Children at Risk 50 Holden Street Providence, R.I. 02903 Phone: 401-453-7635 Fax: 401-453-7639 Email: masullivan@wihri.org