Longterm Outcomes_10.16.13


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  • Every year, millions of women risk their lives giving birth; nearly half of all maternal deaths and one-third of stillbirths occur during childbirth. Improving maternal and child health is essential for the sustainable health of families and communities.
  • In developed nations, most low-birthweight infants are preterm. In under-developed nations, the proportion of term low-birthweight infants is higher due to the greater prevalence of malnutrition.
    The relative influences
    of gestational age and fetal growth
    are difficult to disentangle completely
    because of correlation
    In the U.S., two-thirds of low-birthweight infants are preterm (<37 weeks), and half of preterm infants weigh less than 2,500 grams. This is explained on the next slide.
  • Advances in neonatal intensive care means that more infants are surviving with disabilities and adverse developmental outcomes
    A real concern, especially for resource constrained settings
    Shifting from a pregnancy comlication to a developmental complication
  • Accounts for 1/3 of infant deaths in USA, 45% cerebral palsy, 35% vision impairment, and 25% cognitive or hearing impairment, 75% of perinatal mortality
    Risk of complications increases with increasing immaturity
    The likelihood of perinatal death decreases substantially as the gestational age at birth increases, especially between 24 and 28 weeks of gestation. The data in this slide comes from a population-based cohort of 8,523 infants born in 1997-98 in Memphis (Mercer BM, 2003) and is typical of national data.
    Preterm infants born before 32 weeks have a substantially increased risk of long-term disability and death: 19 percent of infants born before 32 weeks die within the first year of life, compared with 1 percent of infants born at 32–36 weeks, and 0.2 percent of infants delivered at 37–41 weeks (Mathews TJ, MacDorman MF, 2006).
    Dose response effect of prematurity
  • Majority of PTB are moderate to late preterm
    Organ maturation is still occuring in this critical time period
    Difficult to parse out the effect of prematurity per se
  • The brain of a preterm infant at 35 weeks weighs only 2/3 of what it will weigh at full term. That means a lot of important things are happening in the brain in those last few weeks. These include growth and alignment of the brain cells, and creating billions of connections that form the functional units that will process messages in the brain. If the baby is born early, the brain continues to grow and develop, but may not develop normally.
    Growth of the cerebellum: muscles and coordination of movement
    Pattern of dendritic connections between neurons
    Cerebellum is one of the most vulnerable areas for preemies because it has a spurt of growth at 30-32 weeks gestation and is complete by 12 months of age
    When born prematurely, the dendritic connections are developing under different circumstances where nutrition and metabolic are key
  • 1/3 of late preterms displayed school problems including ADD and hyperactivity (19%), poor performance in fine motor skills and writing (32%)
  • Preterm & LBW infants have higher systolic blood pressure later in life
  • Left ventricle- equals the effect assocaited with a 9kg/m2 BMI increase
    Aortic- an effect that exceeds that of smoking during pregnancy
  • The effect of prematurity on LV mass equaled the effect that can be associated with a 9 to 10 point higher BMI
  • Retrospective cohort study of children born between 34 and 42 weeks monitored from birth to 18 months
  • Affects parent child interactions- May increase difficulities in maternal bonding
    Mothers of preemies report more negative experience of birth even six years later and negative experience of first contact with infant
    Feeling that baby did not belong to them. Mothers with brief contact had better bonding with newborn
    Mothers who display PTSD symptoms tend to view their children as more difficult and less easily soothed
    Parents of preemies may continue to view child as vulnerable resulting in rigid, overprotective parenting styles
  • Health-care costs
    e.g., monetary value related to use of community health services
    Educational costs
    e.g., additional assistance (such as special education) required as a result of school failure & learning problems
    Social service costs
    e.g., utilization of developmental services such as day care programs, case management & counselling, or respite care & residential care
    Out-of-pocket expenses
    e.g., additional travel costs related to going to health & social care providers or accommodation expenses
    This slide identifies the various sources for additional long-term care costs associated with premature and low-birthweight (LBW) infants. Economic studies examining the long-term care costs of premature infants are limited. In a 2001 review article by Petrou et al., the authors examined the existing literature and provided some long-term care cost estimates associated with premature and low-birthweight infants. The authors categorized costs and economic consequences related to health care, education, social services and out-of-pocket expenses following the infants’ initial discharge from the neonatal unit. While they acknowledge the differing methodologies used in studies, the review showed higher long-term care costs for preterm or LBW compared to term infants. The authors also note that some studies were based on British cohorts and may not be generalizable to infants born in the U.S. health-care system. A more recent study in England compared the “mean societal costs” of 241 preterm children (20-25 weeks of gestation) against 160 term children during their sixth year after birth. The authors linked unit costs associated with use of health, social and other services or resources for each child during a 12-month period and found a statistically significant higher mean cost difference of $10,600 (converted to U.S. dollars) per preterm child. Again, one of the authors’ conclusions was that extreme preterm birth was “a strong predictor of high societal costs” (Petrou S et al., 2006).
    Sources: Petrou S, Sach T, Davidson L. The long-term costs of preterm birth and low birth weight: results of a systematic review. Child Care Health Dev. 2001;27:97-115; Petrou S, Henderson J, Bracewell M et al. Pushing the boundaries of viability: the economic impact of extreme preterm birth. Early Hum Dev. 2006;82:77-84.
  • Longterm Outcomes_10.16.13

    1. 1. Preterm Birth, So What? Long term health outcomes of prematurity Courtney Gravett, MPH Courtney.gravett@seattlechildrens.org CORE Group Fall 2013
    2. 2. Magnitude of the problem •15 million babies born preterm every year •2nd leading cause of under-5 mortality: • Preterm birth and stillbirth take more newborn lives than HIV, TB and malaria combined. •Preterm birth is the most frequent cause of infant mortality and morbidity in United States
    3. 3. What is Preterm? Classification by gestational age: • Late Preterm: 34-36 weeks • Moderately Preterm: 32-33 weeks • Very Preterm: 28-31 weeks • Extremely Preterm < 28 weeks Classification by birth weight: • Low birth weight (LBW) < 2500 g • Very low birth weight (VLBW) < 1500 g • Extremely low birth weight (ELBW) < 1000
    4. 4. Overlap in LBW and Preterm Births Among LBW: 2/3 are preterm LBW 7.9% Among preterm: more than 43% are LBW (some preterm are not LBW)) Source: National Center for Health Statistics, 2003 file. Prepared by the March of Dimes Perinatal Data Center, 2006.
    5. 5. Why it matters •Increased survival of preterms and the rise in associated long term health consequences represent a significant public health concern •The long-term medical, educational, and productivity costs borne by the individual, as well as by the family and society, are significant but not well understood. •Recent research indicates that PTB has multiple, systemic, longstanding effects on development and disease risk later in life
    6. 6. PTB and disease risk throughout the lifetime Respiratory distress syndrome, necrotizing entercolitis, intraventricular hemmorhage, retinopathy of prematurity sepsis, mortality, feeding problems ~10% of births Mothers at risk for depression, anxiety, future Cerebral preterm labor palsy, developmental delay, higher morbidity & mortality, behavior and learning problems, asthma Diabetes/insulin resistance, hypertension, reduced fertility Source: Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004.
    7. 7. Risk is directly related to degree of immaturity & modified by other factors 28 wk 32 wk 36 wk 40 wk Risk Prenatal exposures Extrauterine exposures Home Environment
    8. 8. Brain growth in the last trimester • The brain is the last major organ to develop • The baby’s brain at 35 wks weighs only 2/3 what it will weigh at term • Lots of important brain growth happens in those last few weeks Image from March of Dimes
    9. 9. Preterm Brain Injury: Long Term Effects • Motor • Cognitive – Hypotonia (initially) – Hypertonia • Cerebral palsy – Spastic diplegia – Delays • Gross • Fine – Delays – Mental retardation • Speech/Language – Delays • Expressive • Receptive Wood N, et al. Neurologic and developmental disability after extremely preterm birth: The EPICure study group. N Eng J Med. 2000; 343(6):378. Baron I, et al. Late preterm birth: A review of medical and neuropsychological childhood outcomes. Neuropsych Rev. 2012; 22:438.
    10. 10. Prematurity and Developmental Disability Prevalence per 1000 children by Gestational Age 20-23 wk 24-28 wk 29-32 wk 33-36 wk >37 wk Cerebral Palsy 49.9 49.9 16.7 3.2 1.3 Mental Retardation 76.0 60.9 27.2 12.9 6.8 Hearing Loss 14.3 6.3 1.9 1.0 0.7 Vision Impairment 11.9 16.1 2.9 1.0 0.5 Developmental disabilities by gestational age among survivors to age 3 Preterm Birth: Causes, Consequences, and Prevention. IOM; Behram RE, Butler AS, editors. Wahington DC: National Academies Press: 2007.
    11. 11. Significant delays seen even in moderate to late preemies Increased long-term developmental delays and decreased IQ for babies born at even 35 - 37 weeks compared to 39 weeks Kerstjens J, et al. Developmental delay in moderately preterm born children at school entry. J Pediatr. 2011; 159:92.
    12. 12. Behavioral and emotional problems Child Behavior Problems Odds ratio Total problems 1.84* Externalizing problems 1.69* Internalizing problems 2.40* Emotionally reactive 1.70 Anxious/depressed 2.50 Somatic complaints 1.92* Withdrawn 1.38 Sleep problems 1.88 Attention problems 1.80 Aggressive behavior 2.03 Risk for clinical problem scores in moderately preterm vs term children at preschool age *indicate significance Potijk M, et al. Higher rated of behavioral and emotional problems at preschool age in children born moderately preterm. Arch Dis Child. 2012:97:112.
    13. 13. Prematurity and Chronic Disease • Preterm birth is a risk factor for: – Cardiovascular disease – Respiratory problems – Psychological problems – Metabolic syndrome – Chronic kidney disease . Goyal 2011, Crump 2011,
    14. 14. Preterm birth and Cardiovascular Health • Preterm birth is an emerging risk factor for – Hypertension (2.5 to 3.8mmHg higher than term) de Jong 2012 – Diabetes (Hazard ration 1.67) Kaijser 2009 – Cardiovascular disease Crump 2011 – Stroke Koupil 2005 • Cardiovascular structure and function are significantly altered after preterm birth – In young adults born preterm, the left ventricular mass is increase and left ventricle smaller – In teenagers born preterm the aortic cross sectional area is 20% smaller Norman M. Premature birth: Implications for cardiovascular health. Future Cardiol. 2013;9:293.
    15. 15. Example: Altered cardiac structure and function into young adulthood • Compared to term infants, preterm infants have – significantly increased left ventricular mass (66.5 g/m2 compared to 55.55 g/m2, p<0.001) – Reduced systolic and diastolic function • This effect was further modified the underlying etiology or prematurity – Maternal preeeclampsia was associated with further reduction in left ventricular strain • This is a clinically meaningful difference that may modify future risk for heart disease Lewandowski AJ, et al. Preterm heart in adult life: Cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry and function. Circulation. 2013; 127:197-206
    16. 16. Preterm birth and asthma • Late preterm birth (34-36 weeks) and low-normal (37-38 weeks) was associated with increased risk of: – Asthma (OR 1.68 LPT) (OR 1.34 low-normal) – Inhaled corticosteroid use (1.66) (1.39 ) low-normal – Number of acute respiratory visits (1.44 LPT) • Late-preterm and low-normal gestational ages may be a risk factor for asthma • Preterm lungs subject to insult from medical intervention Goyal NK, Fiks AG, Lorch SA. Association of late-preterm birth with asthma in young children: practicebased study. 2011. Pediatrics; 128(4)
    17. 17. Impact on mother and family • Mothers of preemies experience more psychological distress than those of term babies – Increased incidence of post-traumatic stress symptoms – At 18 months only 30% of preterm moms had secure attachment to babies, compared to 60% of term moms • Parents of preemies may continue to see children as vulnerable, even when child is no longer medically fragile • Increased economic burden on family Latva R, et al. How is maternal recollection of birth experience related to behaviorial and emotional outcome of preterm infants? Ear Hum Develop. 2008;84:587. Shaw R, et al. Prevention of posttraumatic stress in mothers with preterm infants. Issues in Mental Health Nursing. 2013;34:578.
    18. 18. Variables that affect the premature infant’s developmental trajectory Gestational age Birth weight Nutrition Smoking Socioeconomic status Medical interventions Mechanical ventilation Infection Brain injury Postnatal growth Health Outcome
    19. 19. Public Health Implications • Increased burden on health care system • Increased costs to society – – – – Healthcare costs Educational costs Social service costs Loss of productivity • Must increase awareness of providers that individuals born preterm are at increased risk of chronic disease • Better linkages between providers and social services • When possible, it is important to maintain pregnancy to full term Petrou S et al. Child Care Health Dev. 2001;27:97-115 Petrou S et al. Early Hum Dev. 2006;82:77-84.
    20. 20. Future Directions • Identify and promote protective factors for child development – e.g. close bond with a caregiver • Provider and family member education to mitigate other risk factors – e.g. discourage smoking, encourage proper nutrition • Take a coordinated approach to postpartum and neonatal care • Early detection and intervention for children with signs of delay or disability- linkage to services • Increase availability and access to known interventions across the MNCH spectrum
    21. 21. Questions?