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Keywords:

  • Disability;
  • guidelines;
  • preterm delivery;
  • treatment;
  • viability

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Guidelines
  5. Acknowledgements
  6. References

Due to ever-improving medical technology over the course of the last century, the limit of viability has been lowered from around 32 weeks of gestation, first to 28 weeks and, in recent decades, to as low as less than 24 weeks. Long-term follow-up studies (Project on Preterm and Small-for-Gestational-Age Infants, Leiden Follow-up Project on Prematurity, Epidemiological Project for ICU Research and Evaluation, Étude Epidémiologique sur les Petits Ages Gestationnels, Extremely Preterm Infants in Belgium), however, have shown high percentages of deaths and/or disabilities at lower gestational ages in surviving children. Many parents and children are burdened with lifelong iatrogenic disabilities. As a result, the Dutch Paediatric Association and the Dutch Society of Obstetrics and Gynaecology have laid down joint rules for the management of expected/threatened preterm delivery.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Guidelines
  5. Acknowledgements
  6. References

Over the last century, the ‘limit of viability’ of newborn infants has changed enormously. Due to the uncertainty about gestational age, birthweight was the main indicator of maturity well into the 1980s, even in the western world. The limit of viability was considered until that time to be birthweight around 800–1000 g. In recent decades, gestational age has become feasible as a measure of maturity, even in societies where the majority of pregnancies are not planned, due to reasonably accurate estimates of the expected date of delivery based on first-trimester ultrasound.

In the 1980s, the limit of viability was considered to be 26 weeks, although some infants survived at even lower gestational ages. Follow-up results from that era in the Netherlands show few or no survivors for gestational age below 26 weeks,1 and in other western countries, only a few percent survived. Since then, advancing technology has enabled survival of ‘micronates’, ‘micropreemies’ and ‘nanonates’. Short-term and long-term follow-up studies have shown high percentages of disabilities in surviving children of 26–31 weeks of gestation born in the 1980s and 1990s.2–7

Recent follow-up studies to 19 years of age showed around 30% of moderate or severe problems in surviving adolescents born at 30–32 weeks, increasing to 40% for those born at 25–26 weeks (Table 1) (S. P. Verloove-Vanhorick, pers. comm.). Higher rates of disability in survivors have been found in recent studies on extremely preterm infants, from 22 to 26 weeks of gestation.8,9 In order to survive, these infants have to be subjected to a long period of very intensive, stressful and often painful treatment.10 Their associated healthcare and educational costs over the ensuing years (including hospital services, social services and educational services) is generally high, implying complex problems in later life.10

Table 1.  Project on preterm and small-for-gestational-age infants in the Netherlands, 1983; follow-up results at 19 years of age
Gestational age (weeks)Percentage of moderate or severe problems in overall outcome
≥3231.1
3128.6
3032.0
2934.1
2835.2
2729.1
25–2639.9

Of preterm infants born at gestational ages of 25 and 26 weeks in the 1980s, only 5% survived without problems, another 5% had one to three mild problems in several areas and 10% had one or more moderate or severe problems; 80% had died, mainly in the neonatal period. With increasing gestational age, these figures gradually improve (Figure 1) (S. P. Verloove-Vanhorick, pers. comm.).

image

Figure 1. Project on preterm and small-for-gestational-age infants in the Netherlands, 1983. Relation between total overall outcome (including mortality) at 19 years of age and gestational age (<32 weeks) in liveborn infants.

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Data from more recent studies in the Netherlands show increased survival but similar or more disabilities (Figure 2).5–7,11 Comparable studies in Western countries show similar results.

image

Figure 2. Project on preterm and small-for-gestational-age infants in the Netherlands, 1983 (POPS 83); Leiden follow-up project on prematurity, 1996–1997 (LFUPP 96–97); condition at discharge from the hospital.

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Guidelines

  1. Top of page
  2. Abstract
  3. Introduction
  4. Guidelines
  5. Acknowledgements
  6. References

Based on the evidence outlined above, the Dutch Paediatric Society has agreed in 2005 the following approach for management of expected or threatened preterm delivery:

  • • 
    Gestational age less than 24 + 0/7 weeks (23 completed weeks of gestation): no predelivery transport of pregnant women (in utero transport of fetus) to level 3 perinatal centre; no antenatal steroid treatment; caesarean section on maternal indication only and neonatal care aiming at comfort of infant and family.
  • • 
    Gestational age 24 + 0/7–24 + 6/7 weeks (24 completed weeks of gestation): predelivery transport; antenatal steroid treatment may be considered; caesarean section on maternal indication only and neonatal care aiming at comfort of infant and family, unless intensive treatment is warranted (e.g. lively infant, probably longer gestational age, parental wish).
  • • 
    Gestational age 25 + 0/7–25 + 6/7 weeks (25 completed weeks of gestation): predelivery transport; antenatal steroid treatment; caesarean section on maternal indication, seldom on fetal indication (e.g. gestational age uncertain) and intensive neonatal treatment, unless care aiming at comfort is warranted.
  • • 
    Gestational age 26 + 0/7 weeks or more (26 completed weeks of gestation or greater): predelivery transport; antenatal steroid treatment; caesarean section also on fetal indication and intensive neonatal treatment.
  • • 
    After birth: if birthweight less than 500 g: comfort care.

It is hoped that the Dutch Society of Obstetrics and Gynaecology will endorse these guidelines, albeit with an amendment for the management at 24 weeks: ‘predelivery transport may be considered for counselling’ (Table 2).

Table 2.  Current management in The Netherlands according to Dutch Paediatric Association
Gestational age (completed weeks)Predelivery transport to level 3Antenatal steroid treatmentCaesarean sectionNeonatal care (delivery room)
  • *

    Predelivery transport may be considered for counselling.

<24Maternal indicationComfort warranted
24+ (?)*May be consideredMaternal indicationComfort, unless intensive care
25++Maternal, seldom fetal indicationIntensive care, unless comfort warranted
26++++

Additional conditions that have been stated are as follows:

  • 1
    A nationwide prospective observational study should be initiated by perinatologists-obstetricians and neonatologists (the Prospective Evaluation of PREterm management at 23–27 weeks of gestation in the Netherlands: PREPRE).
  • 2
    Prospective parents should be fully informed, advised and counselled on chances of survival and risks of disability.

The parents’ views and feelings are paramount in the Netherlands. If they object to the start of intensive treatment, Dutch neonatologists will mostly respect their wishes, which is contrary to many other European neonatologists.12

In general, end-of-life decisions are considered feasible in the Netherlands in three situations:

  • 1
    Treatment is useless, the child will die.
  • 2
    Treatment is pointless, futile, not in the child’s interest, extremely poor prognosis after survival.
  • 3
    Treatment causes severe and endless suffering for child and family.13

In infants born at the limits of viability, all three situations may apply. The ethical and moral considerations follow the main Hippocratic principle: ‘nil nocere’, i.e. do no harm.14 It is argued that at gestational ages of 24 weeks and below, the amount of ‘good’ (less than 10% intact survival) does not justify the amount of ‘harm’ done (10–20% disabilities, 70–80% mortality after a period of intensive treatment). At 25 weeks and above, the balance seems to be more favourable (20–30%, 12–24% and 52–56%, respectively). At all gestational ages, however, the guidelines leave room for deviation in individual-specific cases, at the discretion of the attending doctors and according to the wishes of the parents. The guidelines provide a framework reflecting the current viewpoint of Dutch neonatologists and obstetricians, with which most Dutch parents agree.

The debate about the limit of viability continues in many countries. Similar recommendations exist in the Swiss Society of neonatology.15 In Italy, the issue is commonly discussed among neonatologists, but the prevailing principle is ‘preservation of life at all costs’, and parents views are not always taken into consideration.16

The viability of newborn infants has been an issue for many years. In 1984, Peter Dunn17 when considering the wording of the Infant life Preservation Act of 1929: ‘any person who, with intent to destroy the life of a child capable of being born alive by any wilful act causes a child to die before it has an existence independent of its mother, shall be guilty of an offence …’ wondered how the phrase ‘capable of being born alive’ should be interpreted. He argued that it must surely mean ‘having a reasonable chance of survival’ and made a plea for intensive treatment, also for newborns with gestation of less than 28 weeks, and thus for centralisation of births of such infants in maternity units with neonatal intensive care facilities.

Considerable progress has been made in the ensuing 22 years. The debate has shifted from 28 to 24 weeks. Further lowering of the limit of viability seems possible only through a fundamental innovation of treatment of these infants, whose organs have not yet matured sufficiently. Until such times, the balance between ‘harm’ and ‘good’ should guide obstetricians and neonatologists as well as parents.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Guidelines
  5. Acknowledgements
  6. References

I sincerely thank Prof Louis Kollée, Prof Harrie Lafeber, Prof Joke Kok, Dr Sylvia Veen, Dr Martin de Kleine and Dr Elysée Hille for their contributions to this study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Guidelines
  5. Acknowledgements
  6. References
  • 1
    Verloove-Vanhorick SP, Verwey RA, Brand R, Bennebroek Gravenhorst J, Keirse MJCN, Ruys JH. Neonatal mortality risk in relation to gestational age and birthweight. Results of a national survey of preterm and very-low-birthweight infants in the Netherlands. Lancet 1986;1:557.
  • 2
    Walther FJ, Den Ouden AL, Verloove-Vanhorick SP. Looking back in time: outcome of national cohort of very preterm infants born in the Netherlands in 1983. Early Hum Dev 2000;59:17591.
  • 3
    Hille ETM, Den Ouden AL, Saigal S, Wolke D, Lambert M, Whitaker A, et al. Behavioural problems in children who weigh 1000 g or less at birth in four countries. Lancet 2001;357:16413.
  • 4
    Anthony S, Ouden L, Brand R, Verloove-Vanhorick P, Gravenhorst JB. Changes in perinatal care and survival in very preterm and extremely preterm infants in the Netherlands between 1983 and 1995. Eur J Obstet Gynecol Reprod Biol 2004;112:1707.
  • 5
    Rijken M, Stoelhorst GMSJ, Martens SE, Van Zwieten PHT, Brand R, Wit JM, et al. Mortality and neurologic, mental, and psychomotor development at 2 years in infants born less than 27 weeks’ gestation: The Leiden Follow-Up Project on Prematurity. Pediatrics 2003;112:3518.
  • 6
    De Kleine MJK, Den Ouden AL, Kollée LAA, Van Baar A, Nijhuis-van der Sanden MWG, et al. Outcome of perinatal care for very preterm infants at five years of age; a comparison between 1983 and 1993. Paediatr Perinat Epidemiol 2006 (in press).
  • 7
    De Kleine MJK, Den Ouden AL, Kollée LAA, Ilsen A, Van Wassenaer AG, et al. Lower mortality but higher neonatal morbidity over a decade in very preterm infants. Paediatr Perinat Epidemiol 2006 (in press).
  • 8
    Marlow N, Wolke D, Bracewell MA, Samara M; EPICure Study Group. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005;352:712.
  • 9
    Vanhaesebrouck P, Allegaert K, Bottu J, Debauche C, Devlieger H, Docx M, et al. The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium. Pediatrics 2004;114:66375.
  • 10
    Petrou S, Henderson J, Bracewell M, Hockley C, Wolke D, Marlow N, et al. Pushing the boundaries of viability: the economic impact of extreme preterm birth. Early Hum Dev 2006;82:7784.
  • 11
    Stoelhorst GM, Rijken M, Martens SE, Brand R, Den Ouden AL, Wit JM, et al. Leiden Follow-up Project on Prematurity. Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age < 32 weeks): the project on preterm and small for gestational age infants 1983 and the Leiden follow-up project on prematurity 1996–1997. Pediatrics 2005;115:396405.
  • 12
    De Leeuw R, Cuttini M, Nadai M, Berbik I, Hansen G, Kucinskas A, et al. Treatment choices for extremely preterm infants: an international perspective. J Pediatr 2000;137:60815.
  • 13
    Verhagen E, Sauer PJJ. The Groningen Protocol: euthanasia in severely ill newborns. N Engl J Med 2005;352:95962.
  • 14
    Kollee LAA. 25 weken als grens voor levensvatbaarheid van de vrucht: ethisch juist [25 weeks as limit of viability of the fetus: ethically correct]. Ned Tijdschr Geneeskd 2005;149:1938.
  • 15
    Berger TM, Büttiker V, Fauchère JC, Holzgreve W, Kind C, Largo R, et al. Swiss Society of Neonatology Guidelines. Recommendations for the care of infants born at the limit of viability (gestational age 22–26 weeks). 2002 [www.neonet.ch/assets/doc/Infants_born_at_the_limit_of_viability_-_english_final.pdf]. Accessed 16 October 2006.
  • 16
    Mesters B. Op een goudschaaltje. Italiaanse richtlijn voor de behandeling van extreme prematuren [In the balance. Italian guideline for treatment of extremely prematures]. Medisch Contact 2006;61:3525.
  • 17
    Dunn PM. Capable of being born alive? Lancet 1984;1:5534.