Extreme Prematurity - Practices, Bioethics, And The Law Part 2 potx

Bottoms et al.46,47 evaluated whether antenatal infor-mation could accurately predict the survival of ELBW infants with and without major morbidity, using data collected in 1992–1993.. T

I N F L U E N C E O F O B S T E T R I C M A N A G E M E N T

How physicians, in particular obstetricians, view and assessviability can affect perinatal survival figures In an Americanstudy(44) that examined the relationship between obstetric careduring labor and delivery and the survival of EPTIs, the authorscompared the outcomes of those who were considered viable ante-natally and those who were not The factors evaluated in the judg-

ment of viability were estimated age (> 26 weeks) and estimated weight (> 650g), lethal anomalies, and parental requests In the

total population studied, some were misclassified (usually weightestimation), or parents had requested aggressive management orthe opposite This “allowed” the authors to study the survival ofinfants who, by their standards, would have been considered non-viable but who received antenatal and perinatal care as if theywere viable Although in some groups the numbers were small,the chances of survival were strongly associated with the ante-natal assessment of viability The odds of survival for all fetusestreated as viable were 17 times the odds for those considered non-viable Birth weight alone did not explain wholly the relationshipbetween antepartum viability assessment and outcome Thus, in

I N F L U E N C E O F O B S T E T R I C M A N A G E M E N T

this study, survival of the EPTI was related to judgments of

viabil-ity that determined their care Silver et al also published similar

findings.(45) These studies, which had relatively small numbers,

do not suggest that there is no limit to fetal viability, but they

do caution the reader to take into account obstetric management

strategies when examining figures concerning the outcome of the

EPTI Obstetricians evaluate antenatal data to make decisions

concerning the management of an anticipated extremely preterm

delivery Bottoms et al.(46,47) evaluated whether antenatal

infor-mation could accurately predict the survival of ELBW infants with

and without major morbidity, using data collected in 1992–1993

The reported findings were that the willingness of an obstetrician

to perform a cesarean section at 24 weeks’ gestation was

associ-ated with an improvement in survival from 33% to 57%, but the

risk of serious morbidity doubled from 20% to 40% Survivals, and

survival without disability, were significantly better when birth

resulted from active medical management, compared to a passive

approach, with or without cesarean section The use of prepartum

ultrasonographic data could not reliably distinguish who would

survive without serious morbidity, although there was a threshold

below which no survivors were found

of an EPTI may not be a good indicator of viability or later come.(52) Jankov, Asztalos, and Skidmore evaluated whether vig-orous resuscitation of ELBW infants at birth improved survival

out-or increased the chances of majout-or neurodevelopmental disability

They reported the outcome of a group of infants born weighing

E F F E C T O F R E S U S C I T A T I O N I N T H E D E L I V E R Y R O O M

750g or less who received CPR (positive pressure ventilation,

car-diac compression,+/− adrenaline) in the delivery room About

57% survived, and 88% were free of major neurodevelopmental

disability at follow-up.(53) Similar findings have been published

by several other authors(54–56) and it does appear that CPR in

the delivery room for the EPTI does not necessarily lead to a large

decrease in survival or an increase in major neurologic sequelae

compared to those who survived following only intubation and

positive pressure ventilation

N AT I O N A L C O M PA R I S O N S

Outcomes for the EPTI may differ from country to try; the reasons include economic resources and access tosophisticated technological care in developing countries and vary-ing attitudes and perceptions in the more developed countries

coun-The latter will be discussed later in this chapter, but here I brieflydocument findings concerning the Netherlands and survival insome developing countries Lorenz et al.(22) reported on the out-come of EPTIs born less than 26 weeks in two population-basedcohorts, New Jersey (NJ), United States and the Netherlands, whoreceived systematically different approaches to their care duringthe mid-1980s In the NJ cohort, almost all babies received inten-sive care, whereas the policy was more selective in the Nether-lands Assisted ventilation was more commonly used in NJ, 95%

versus 64%, and almost all the difference resulted from the use ofassisted ventilation in infants who subsequently died Mortality

at 28 days was about 46% in NJ and 73% in the Netherlands

No infant less than 25 weeks’ gestation survived to 28 days inthe Netherlands Survival to 2 years in NJ was twice that in the

N A T I O N A L C O M P A R I S O N S

Netherlands The prevalence of disabling cerebral palsy was 17.2%

among survivors in NJ and 3.4% in the Netherlands In the NJ

cohort, 1,820 ventilator days were expended per 100 live births

compared to 448 days in the Netherlands, but the difference in

nonventilator days was not statistically different In summary, the

management approach in NJ resulted in 24 additional survivors

per 100 live births, 7 additional cases of disabling cerebral palsy

per 100 live births, and at a cost of 1,372 additional ventilator

days per 100 live births.(22) That there is a significant difference

in approach to the management of the EPTI in the Netherlands

compared to NJ that is of great consequence is clear How this

is accomplished can be found in an article by Van der Heide and

associates published in 1997.(57) They reported on end of life

deci-sions for neonates in the Netherlands, and although only some of

the babies were EPTIs, it does reflect attitude and practice In the

report, they stated that 57% of all infant and neonatal deaths had

been preceded by a decision to forego life-sustaining treatment,

and was accompanied by the administration of potentially

life-shortening drugs to relieve pain or other symptoms in 23% and

by the administration of drugs with the explicit aim of hastening

death in 8% Parents were involved in 79% of decisions.The most

common reason for not involving parents was stated as “it was so

obviously the only correct decision.”(57)

The rates for neonatal mortality differ between developing anddeveloped countries, as does the practice of neonatal care Most

worldwide neonatal deaths occur in the developing world, and at

least one-third of these are in preterm infants.(58,59) In a study

published in 2003,(58) the mortality rate for infants born at 28–

29 weeks was 478 per 1,000 live births in a geographically diverse

group of developing countries (Brazil, Colombia, Thailand, India,

and the Philippines) compared to 83 in two developed countries

T H E E X T R E M E L Y P R E T E R M I N F A N T

(United States, Ireland) In the developing countries, tions such as surfactant, ventilators, blood gases, and oximetrywere variable, and several physicians considered pregnancies lessthan 28 weeks nonviable How physicians judge viability affectsperinatal interventions and mortality not only in developed coun-tries but also in developing ones

P R E D I C T I O N O F O U T C O M E

There can be substantial error rate when physicians estimate

outcome for the EPTI.(60–63) Tyson and associates(30)reported error rates of 52% and 21% in the prediction of death

and survival for infants weighing 501–800g at birth Despite the

requirement that physicians practice according to the best

avail-able evidence, this may not always be the case, and in such

circum-stances they may incorrectly estimate the chances of death and

disability,(64) which affects their decisions as well as the

counsel-ing of parents.(44,60)

In 2001, it was reported that at the University Medical Center

in Leiden, a leading center for the the treatment of preterm infants

in the Netherlands, a decision, in principle, was taken to stop

active intensive treatment of babies born less than 25 weeks’

ges-tation.(65) However, the head of neonatology at the center stated

that, “infants born before 25 weeks would still be given ‘vigorous

support’ if the parents wished and the medical team considered

the infant viable at birth.”(65) The decision was made because,

in their study of premature births from 1996 through 1997, 66%

of those born at 23 and 24 weeks died, and half the survivors had

severe physical or mental handicaps.(65)

L I M I T O F V I A B I L I T Y

Although there is no sharp demarcation point, over time thelimit of viability has become progressively lower, from a birthweight of 1,500g before 1940, to 1,000g and 28 weeks’ gestation

by the 1970s.(20) Survival is now common for infants of lessthan 750g and for those of 25 weeks’ gestation The lower limit

of viability appears, at present, to be approximately 22–23 pleted weeks of gestation, with survival and morbidity improvingmarkedly with each later week of gestation It is now governed bytechnological capacity, medical intervention, and the attitudes ofthe medical profession.(63,66)

M O R B I D I T Y

Extremely preterm birth is associated with several

morbidi-ties ranging from the very severe to the relatively mild, andthe risk increases as gestational age decreases.(67) The morbidi-

ties include cerebral palsy, mental retardation, learning and

lan-guage disability, disorders of attention and behavior, visual and

hearing impairment, chronic lung disease, gastrointestinal

dys-function, and poor growth.(68–74) Furthermore, survivors may

require prolonged hospital stays, in-home nursing and

technolog-ical services, and societal and state support, all of which add to

emotional and financial family burdens.(75,76) Although there

is some relationship between disorders of higher brain

func-tion and psychosocial, socioeconomic, and environmental

fac-tors,(77,78) there is now substantial evidence that

neurodevelop-mental disability arises from poor brain development apart from

frank parenchymal brain injury Former EPTIs have been reported

to show decreased regional brain volumes, compared to term

con-trols, including reduced volumes of cortical gray matter, the

hip-pocampi, and corpus callosum, in addition to an increase in the

out-be variability in the results both within and out-between countries.

The causes include variable perinatal and neonatal practices; caseascertainment and attrition rates; gestational age limits and birthweight restrictions; age at follow-up; diagnoses sought; criteria fordisability with differing definitions and inclusions; and the use ofdifferent methodologies when assessing outcome, including a fail-ure to use concurrent norms.(20,31,88–93) But despite a plethora

of outcome studies, there is a relative dearth of reports on thefunctional outcome of disabilities and their effect on quality oflife.(31,94) The characteristics of different national populationsstudied, and the conduct of their health delivery systems, may alsoappear to affect the statistics reported, even when these popula-tions are geographically close Field and colleagues(95) comparedthe neonatal intensive care services of two European countries, the

UK and Denmark, during the period 1994–1995; these countrieshave different approaches to neonatal intensive care The popu-lations compared were live born infants 22–27 weeks’ gestation

or less than 1,000g The British services were more centralizedand specialist based, but they had higher rates of prematurity andsicker babies with worse outcomes, despite the delivery of moreintensive care The authors rejected the notion that this was theresult of systematically worse care and suggested it was “a reflec-tion of innate reproductive health in the two countries” and socialcircumstances, as the teenage pregnancy rate was about four timeshigher in the UK,(96) as well as the lower social spending perhead of population.(97)

El-Metwally et al.(21) determined neonatal morbidity ratesfor infants born in Rhode Island, United States, during the 1990s,

M O R B I D I T Y

at 22 to 25 weeks’ gestation The rate of severe

intraventricu-lar hemorrhage or periventricuintraventricu-lar leukomalacia was 27% but was

higher at lower gestational ages Chan and associates(34) reported

the neonatal morbidity for babies born less than 26 weeks, in 17

Canadian centers, during 1996 and 1997 Major neonatal

mor-bidity, defined by the authors as grades III or IV intraventricular

hemorrhage, stage 3 or worse retinopathy of prematurity (ROP),

chronic lung disease, and necrotizing enterocolitis, was found in

some form in 77% The percentage was 89% at 22 weeks and 71%

at 25 weeks As with survival, there was wide intercenter

vari-ation with survival without major early morbidity ranging from

0% to 26% Vohr and associates, in a U.S multicenter cohort

study,(98) reported the outcome of 1,151 ELBW infants at a

cor-rected age of 18 to 22 months This number represented only 78%

of the total survivors, which could represent an underestimate of

the disability rate.(91) Abnormal neurologic examinations were

found in 25% and an abnormal Bayley Mental and Psychomotor

Developmental Index of less than 70 in 37% and 29% respectively

Vision impairment occurred in 9%, hearing impairment in 11%,

and cerebral palsy in 17% The probability of abnormal

neurolog-ical findings increased as birth weight decreased – 25% for birth

weights 901–1,000g and 43% for those weighing 401–500g The

risk of cerebral palsy also increased with decreasing birth weight –

15% for 901–1,000g and 29% for 401–501g In a prospective

population-based study from the UK and Ireland, Wood et al.(42)

published the outcome of infants born less than 26 weeks’

ges-tation during a 10-month period, beginning in March 1995, who

were admitted to a NICU The survivors were assessed at a median

age of 30 months after the expected date of delivery The mean

Bayley Mental Developmental Index was 84 +/− 12, and the

mean Psychomotor Developmental Index was 87+/− 13

Nine-teen percent of the children had scores more than 3 standard

T H E E X T R E M E L Y P R E T E R M I N F A N T

deviations below the mean and were classified as severely disabled

There were 11% who scored between 2 and 3 standard deviationsbelow the mean (“other disability”) Interestingly, the scores didnot vary substantially with gestational age, but boys had signif-icantly lower psychomotor scores than girls Cerebral palsy wasdiagnosed in 18%, and in about one-half of these it was charac-terized as severe Again there were no differences related to ges-tation About 2% were blind, and 3% had uncorrectable hearingloss Overall, 23% were reported to have severe disability in thedevelopmental, neuromotor, sensory, or communication domains

In a multicenter study involving NICUs in Canada, the UnitedStates, Australia, and Hong Kong,(99) on infants born weighing500–999g between 1996 and 1998, 18% developed cerebral palsy,26% had cognitive impairment, 2% had hearing loss requiringamplification, and 2% had bilateral blindness In San Francisco,Piecuch et al.(100) reported on 24- to 26-week gestation survivors

About 25% had a developmental quotient of less than 70, and 14%

had cerebral palsy When the same group reported on a larger ber of infants of ELBW born between 1979 and 1991, and reported

num-on in 1997,(101) about 14% were reported to have cerebral palsy,1% were blind, 0.2% were deaf, and 14% had cognitive dysfunc-tion Other reports have placed the risk of cerebral palsy at earlyfollow-up as between 7% and 18%.(102–106)