904

of putative and committed bone cells of the distractioncallus are different from either those of fracture callusor of normal bone. It then follows that the balancebetween the various factors controlling the phenotypeof connective tissue cells, and even the factors

themselves, will likewise be different.If we can unravel the mechanisms involved in this

particular type of new bone formation, our

understanding of the control of osteogenesis, and byimplication our ability to influence it, would beincreased. Techniques that allow the biochemistry ofsingle cells to be explored within their natural

environment—eg, immunohistochemistry and in-situhybridisation—are clearly the way forward.

1. Paterson D. Leg lengthening procedures: a historical review. Clin OrthopRel Res 1990; 250: 27-33.

2. Ilizarov GA. Clinical application of the tension-stress effect for limblengthening. Clin Orthop Rel Res 1990; 250: 8-26.

3. Macdonald BR, Gowan M. Cytokines and bone. Br J Rheumatol 1992;31: 149-55.

4. Joyce ME, Jingushi S, Bolander ME. Transforming growth factor beta inthe regulation of fracture repair. Orthop Clin N Am 1990; 21: 199-209.

5. Andrew JG, Hoyland JA, Andrew SM, Freemont AJ, Marsh DR.Demonstration of TGFbeta mRNA by in situ hybridisation in humanfracture callus. Calcif Tissue Int (in press).

6. Kojimoto H, Yasui N, Goto T, Matsuda S, Shimomura Y. Bonelengthening in rabbits by callus distraction: the role of periosteum andendosteum. J Bone Joint Surg 1988; 70B: 543-50.

7. Deloye C, Delefortrie G, Coutelier L, Vincent A. Bone regeneration incortical bone during distraction lengthening: an experimental study.Clin Orthop Rel Res 1990; 250: 34-42.

8. Aronson J, Good B, Stewart C, Harrison B, Harp J. Preliminary studiesof mineralisation during distraction osteogenesis. Clin Orthop Rel Res1990; 250: 43-49.

9. Shearer JR, Roach HI, Parsons SW. Histology of a lengthened humantibia. J Bone Joint Surg 1992; 74B: 39-44.

10. Hoyland JA, Hopkinson I, Odedra R, Freemont AJ. Detection of type Icollagen mRNA in routine bone biopsies. Matrix 1990; 10: 241.

Clinical management of trisomy 18How should one manage a sick newborn infant with

multiple malformations? The paediatrician who isconfronted by distraught parents and an ill baby withunclear diagnosis and uncertain prognosis is in a mostunenviable position. The report by Bos and colleagueson p 913 focuses specifically on the dilemmas that arisewhen a baby suspected of having trisomy 18

(Edwards’ syndrome) presents at or shortly after birthwith a life-threatening malformation.The natural history of trisomy 18 makes gloomy

reading. The live-born incidence is about 1 in

3000-5000, although in centres where detailed

ultrasonography for fetal anomalies is routinelyavailable many affected babies will be detected duringthe second trimester. For those born alive the outlook,both qualitative and quantitative, is poor. In 1967 itwas estimated that median life expectancy was about 2months.1 More recently, values of 2-5-6 days havebeen obtained; 90% of babies with full-blown trisomy18 die within 3 months of birth. Affected babies whosurvive beyond infancy are invariably very severelyhandicapped.5,6

It is against this backdrop that the neonatal team hasto decide how best to care for an infant in whom this

diagnosis is suspected. Management decisions aremade even more difficult if, as is likely, the baby has alife-threatening malformation such as oesophagealatresia or diaphragmatic hernia. Early confirmation ofthe diagnosis will at least enable the paediatrician, withthe help of surgical, nursing, and pastoral colleagues,to provide accurate and objective information andcounselling. As Bos et al indicate, bone marrowkaryotyping will usually provide an answer within afew hours, although the poor quality of chromosomepreparations obtained with this approach will

preclude the diagnosis of all but the most grosschromosome abnormalities. At least 24 and moreoften 48-72 h must elapse for a more defmitivechromosome analysis with cultured lymphocytes.Having established the diagnosis, subsequent

management of the baby should involve full and

lengthy discussion with the parents; most

paediatricians would advise that major surgery islikely to inflict unnecessary suffering, since life

expectancy is poor whichever policy is pursued. Theoffer of a second opinion and access to relevantmedical publications may help. (In the UK, parentscan turn to SOFT UK, the Support Organisation ForTrisomy 13/18.) After counselling, parents usuallyconclude that a policy of non-intervention is in theirbaby’s best interests. However, subsequentmanagement of such a baby remains an ethical

minefield;7,8 most but not all professional carers adopta policy of keeping the infant warm, nourished,hydrated, and free from pain while awaiting theinevitable outcome.Some parents, for whatever reasons, request that

active measures be instituted to maximise their child’s

prospects for survival. In these circumstances carersshould remember that not all parents regard the birthof a handicapped baby as a tragedy and that some willderive comfort in the years to come from the

knowledge that their baby was given "every possiblechance".There will never be easy answers to such heart-

rending decisions. The best that medical and nursingstaff can do is to act in good faith and with completeopenness. If a rapid diagnosis helps ease both theirdilemma and that of the parents, this is a worthwhile

development.

1. Weber WW. Survival and the sex ratio in trisomy 17-18. Am J Hum Genet1967; 19: 369-73.

2. Young ID, Cook JP, Mehta L. Changing demography of trisomy 18.Arch Dis Child 1986; 61: 1035-36.

3. Carter PE, Pearn JH, Bell J, et al. Survival in trisomy 18. Clin Genet 1985;27: 59-61.

4. Goldstein H, Nielsen KJ. Rates and survival of individuals with trisomy13 and 18. Clin Genet 1988; 34: 366-72.

5. Mehta L, Shannon RS, Duckett DP, et al. Trisomy 18 in a 13 year oldgirl. J Med Genet 1986; 23: 256-57.

6. Smith A, Field B, Learoyd BM. Trisomy 18 at age 21 years. Am J MedGenet 1989; 34: 338-39.

7. Walters JW. Approaches to ethical decision making in the neonatalintensive care unit. Am J Dis Child 1988; 142: 825-30.

8. Miraie ED, Mahowald MB. Withholding nutrition from seriously illnewborn infants: a parent’s perspective. J Pediatr 1988; 113:262-65.