Preterm Birth, So What?Long term health outcomes of prematurity

Courtney Gravett, MPHCourtney.gravett@seattlechildrens.org

CORE Group Fall 2013

•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

Magnitude of the problem

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

Source: National Center for Health Statistics, 2003 file. Prepared by the March of Dimes Perinatal Data Center, 2006.

Overlap in LBW and Preterm Births

Among LBW: 2/3 are preterm

Among preterm: more than 43% are LBW (some preterm are not LBW))

LBW7.9%

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

PTB and disease risk throughout the lifetime

Cerebral palsy, developmental delay, higher morbidity & mortality, behavior and learning problems, asthma

~10% of birthsMothers at risk for depression, anxiety, future preterm labor

Respiratory distress syndrome, necrotizing entercolitis, intraventricular hemmorhage, retinopathy of prematurity sepsis, mortality, feeding problems

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.

Risk is directly related to degree of immaturity & modified by other factors

28 wk 32 wk 36 wk 40 wk

Prenatal exposures

Extrauterineexposures

Home Environment

Risk

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

Preterm Brain Injury: Long Term Effects

• Motor– Hypotonia (initially)– Hypertonia

• Cerebral palsy– Spastic diplegia

– Delays• Gross• Fine

• Cognitive– 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.

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

Prematurity and Developmental Disability

Preterm Birth: Causes, Consequences, and Prevention. IOM; Behram RE, Butler AS, editors. Wahington DC: National Academies Press: 2007.

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.

Behavioral and emotional problems

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.

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

.

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,

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.

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

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

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: practice-based study. 2011. Pediatrics; 128(4)

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.

Variables that affect the premature infant’s developmental trajectory

Infection

Socioeconomic status

Gestational age

Birth weight

Mechanical ventilation

Brain injury

Medical interventions

Nutrition

Smoking

Postnatalgrowth

Health Outcome

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.

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

Questions?