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Impact of prenatal diagnosis on neonatal surgery
Semin Neonato11996; 1:177-184
Impact of prenatal diagnosis on neonatal surgery Evelyn H. Dykes and Ross M. Fisher
South East Thames Congenital Malformation Registry, Children's Hospital, Lewisham, London, UK
Key words: prenatal diagnosis, ultrasound, neonatal surgery, congenital abnormality
Prenatal ultrasound diagnosis has radically altered neonatal surgical practice. Advance warning of severe structural malformations allows time for detailed parental counselling by neonatal surgeons in conjunction with obstetricians and neonatologists, so that the parents of an infant with an abnormality may be adequately prepared for the investigations and surgery which will be required after birth. Prenatal diagnosis also creates opportunities for interventions during pregnancy such as fetal karyotyping, in-utero transfer and planned delivery in a perinatal centre where neonatal surgical and anaesthetic expertise is readily available. Selective termination of fetuses found to have chromosomal abnormalities or such severe abnormalities that survival is unlikely, results in relatively 'good-risk' populations presenting to neonatal surgeons after birth. Consequently, survival rates after surgery have improved in many conditions. Neonatal surgeons should be informed of any prenatal diagnosis of a surgical abnormality and should be actively involved in parental counselling and perinatal management.
Introduction The increasing use of high resolution fetal sonography in routine antenatal care or as an adjunct following demonstration of raised maternal serum c~-fetoprotein has resulted in the early identification of many surgically correctable fetal malformations. Advance warning of these conditions has radically altered neonatal surgical practice with respect to parental information, patient populations and outcome after surgery. In the past, neonatal surgeons only became aware of an infant with an abnormality after delivery. In most cases the baby was delivered in a district hospital, necessitating an urgent transfer to the neonatal surgical centre for assessment and surgery. In many instances the parents, particularly the mother, were unable to accompany the baby and often did not meet the surgeon until any urgent surgery was completed. In some tragic situations, notably diaphragmatic hernia, the baby died before specialist surgical consultation could be obtained. Correspondence:E.H.Dykes,Departmentof PaediatricSurgery.Children's ttospital. Lewisham.LondonSE136LILUK. 1084-2756/96/030177+ 08 $12.00/00
Nowadays it is unusual for such unsatisfactory situations to occur. The majority of severe structural malformations are identified before birth and in optimal circumstances, the parents will have met a neonatal surgeon at an early stage of the pregnancy to discuss the nature of the malformation, postnatal management (including investigations and surgery) and likely outcome, taking into account factors such as chromosome abnormalities or multiple anomalies. Furthermore, for infants with malformations which may require immediate or urgent surgery, arrangements for planned delivery in a neonatal surgical centre can be made well in advance, permitting optimal perinatal management as well as parental presence throughout. Contingency plans for unexpected preterm labour can also be made and discussed with the local obstetricians and paediatricians. Good communication throughout is paramount, since, if the best outcome for the infant and family is to be achieved, all clinicians involved (including the general practitioner, local obstetrician and local neonatologist, as well as fetal medicine specialists, neonatologists and surgeons in the tertiary centre) must be kept informed of any decisions. Parents of © 1996 W.B. Saunders Company Ltd
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a baby with a surgical condition requiring neonatal intensive care often find it helpful to visit the perinatal centre in advance of the birth to familiarize themselves with the location, layout and staff of the unit concerned. Perhaps the most important factor in planning the optimal neonatal surgical care of an infant with a prenatally-diagnosed surgical malformation is a knowledge of the likely accuracy of the prenatal diagnosis. Inevitably this varies, depending on the condition and organ system in question and on the expertise and experience of the sonographer. It is essential that all fetuses with a suspected surgical anomaly are referred to a specialist fetal medicine unit for confirmation and most such units incorporate multidisciplinary diagnostic and counselling facilities. Even there however, a specific diagnosis may not be assured. Appreciation of the limitations of prenatal diagnosis is important for both clinicians and parents. In order to evaluate the accuracy and impact of prenatal ultrasound diagnosis, a number of population-based registries have been established [1-3]. The benefit of such registries is that they do not rely on single centre reports which, although valuable, do not reflect the experience of the population as a whole. Data on interventions and outcomes of each pregnancy are also held by registries. Knowledge of local prenatal diagnostic accuracy rates and outcomes for different malformations gives an up-to-date perspective on the current status of prenatal diagnosis and provides important information for those involved in counselling and postnatal care. The data reported below are derived from the experience of the South East Thames Congenital Malformation Registry from I992-I995 and reflect the impact of prenatal diagnosis in selected surgical conditions based on a population of 3.5 million with an annual birth rate of 52 000.
South East Thames Congenital Malformation Registry The South East Thames Congenital Malformation Registry was established in April 1992 as the result of an initiative supported by the Regional Medical Audit Committee. Notification of all identified cases of major congenital structural abnormalities diagnosed pre- or postnatally is requested from all obstetric, fetal medicine, paediatric and pathology
E. H. Dykes & R. M. Fisher
Figure 1. Fetal ultrasound of diaphragmatic hernia at 18 weeks gestation showing the stomach next to the heart which is shifted to the right side.
units in the region. Once notified of a case, the registry co-ordinator collects data on the time and method of diagnosis, any prenatal interventions, time and place of delivery, nature of abnormalities and ultimate outcome up to I year after birth. All data are collected and maintained according to the regulations of the Data Protection Act (1994).
Prenatal diagnosis of selected neonatal surgical abnormalities Congenital diaphragmatic hernia Congenital diaphragmatic hernia remains one of the commonest and most controversial surgical abnormalities. Prenatal diagnosis is based on visualization of the fetal stomach above the diaphragm beside the heart, often in association with demonstrabte fetal lung hypoplasia and mediastinal shift (Fig. 1). Polyhydramnios may be present (possibly as a result of impaired fetal swallowing secondary to oesophageal compression) and part of the liver may also be seen within the chest. It was previously held that infants with a prenatal diagnosis of a congenital diaphragmatic hernia had a poorer prognosis than those not identified prenatally [4]. However, recent experience suggests that prenatal diagnosis may not alter the outcome; data from the South East Thames Congenital Malformation Registry shows that the 1-year survival rate for the 43 infants with prenatally diagnosed diaphragmatic hernia equalled that for the 16 with unsuspected lesions (69.8%
Impact of Prenatal Diagnosis on Neonatal Surgery
179
Table 1. Prenatal diagnosis and outcome in selected surgical malformations reported to South East Thames Congenital Malformation Registry during a three year period (1992-1995) Malformation
Diaphragmatic hernia Cystic lung lesions Oesophageal atresia Duodenal atresia AnorectaI atresia Exomphalos Gastroschisis Bladder exstrophy Posterior urethral valves Myelomeningocoele
Confirmed cases
73 21 43 20 79 40 40 5 41 77
Prenatal diagnoses (%)
52 19 6 11 0 39 38 2 35 61
(71) (90) (14) (55) (0) (98) (95) (40) (85) (79)
versus 68.7%), while for isolated diaphragmatic hernias (n=49), 1-year survival in the prenatally diagnosed group was 79% compared with 73% for infants with unsuspected hernias. Gestational age at diagnosis does not appear to be relevant to outcome; there was no difference between survivors and deaths in this respect. Approximately 30% of infants in each group were diagnosed before 20 weeks gestation. It is likely that more refined prenatal diagnosis contributes to a greater proportion of cases being identified prenatally, with the result that earlier apparent differences in outcome are now insignificant. However, in view of the significant incidence of associated malformations (particularly cardiac) which may adversely affect survival [5] a careful prenatal search for other abnormalities is essential. In infants with multiple anomalies, the prognosis may be so poor that the parents opt for termination of the pregriancy. Consequently, fetuses surviving to delivery may be a selected 'low-risk' group, whose survival depends entirely on the degree of lung hypoplasia and may in fact be better than that seen previously in 'all-comers' (Table 1). Additionally, prenatal diagnosis permits optimal planning of delivery and neonatal resuscitation, which may independently improve survival.
Cystic abnormalities of the lung Congenital cystic abnormalities of the lung include cystic adenomatoid malformations, isolated lung cysts and pulmonary sequestrations. Although it is possible to demonstrate cysts within the fetal lung
Terminated
I1 2 4 1 17 23 2 2 3 55
Live-born (%)
59 18 38 16 50 14 34 3 38 7
(81) (86) (88) (80) (63) (35) (85) (60) (93) (9)
Alive at I year (% live births)
41 (70) 17 (94) 34 (89) 15 (94) 47 (94) 11 (79) 33 (97) 3 (100) 36 (95) 7 (100)
on sonography, it is rarely possible to be specific about a precise diagnosis prenatally [6]. Persistent large lesions causing mediastinal shift are most likely to require urgent neonatal surgery, but even in such cases the clinical symptoms after delivery may be mild. A significant proportion of prenatally diagnosed lung cysts regress during pregnancy and some have been seen to disappear completely [6]. Consequently, caution is required when making a prognosis on such anomalies prenatally. If a cystic lung abnormality is detected, serial scans are helpful in following the progression of the lesion. Those which persist to delivery will require further investigation, and the need for surgical removal must be considered. Of 21 confirmed cystic lung lesions identified from the South East Thames Congenital Malformation Registry during a 3-year period, 19 (90%) were identified prenatally and 17 (94% of live births) were alive at one year of age (Table 1). These results suggest that the spectrum of disease being identified prenatally is wide and is likely to include minor malformations which might previously have remained undiagnosed. Certainly the symptoms in this group are significantly different from those reported in previous studies of postnatally identified congenital cystic adenomatoid malformation (CCAM) [7]; in our experience, most infants with prenatally diagnosed CCAM have no symptoms at birth and may in fact have normal chest X-rays for several months. A previous report has highlighted the difficulties in distinguishing between CCAM and other cystic lung lesions in the fetus [6]; caution should be exercised when making precise prenatal diagnoses in such malformations.
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E.H. Dykes & R. M. Fisher
Oesophageal atresia Oesophageal atresia results in impaired swallowing of amniotic fluid by the fetus, and consequently may give rise to polyhydramnios. Sonographic demonstration of the fetal oesophagus is difficult if not impossible, and the diagnosis is usually made on circumstantial evidence. In some cases (without a tracheo-oesophageal fistula) absence of the normally visible fetal stomach in the presence of polyhydramnios may raise the possibility of an atresia. However, since the most common form of oesophageal atresia is associated with a fistula between the trachea and the distal oesophagus [8], fetal breathing movements may allow amniotic fluid to pass into the stomach, which thus appears sonographically normal. It is not surprising therefore, that currently, the majority of oesophageal atresias remain undetected until after delivery (Table 1). In cases suspected prenatally, it is wise to consult the local neonatal surgical centre, since urgent surgery is likely to be required (particularly in cases with an associated fistula to the trachea), and delivery at a perinatal centre may be advised. Oesophageal atresia is often associated with other malformations [8], and a prenatal sonographic search for anomalies of the heart, skeleton and kidneys is essential. Chromosome abnormalities are infrequent (approximately 10%) but if oesophageal atresia is suspected, fetal karyotyping may be helpful for prognostic purposes.
Duodenal obstruction Duodenal obstruction may be caused by atresia, stenosis, annular pancreas or malrotation. In the fetus, duodenal obstruction results in distension of the stomach with secondary polyhydramnios; it is rarely possible to distinguish the cause of the obstruction prenatally. Occasionally the characteristic postnatal double-bubble' sign is seen sonographically (Fig. 2). The commonest malformation is duodenal atresia, which is associated with Down's syndrome in 30% of patients [9]. The presence of polyhydramnios in association with other sonographic markers of karyotype abnormality may lead to a suspicion of duodenal atresia; conversely, a diagnosis of fetal duodenal obstruction should trigger a sonographic search for other markers of chromosome anomaly and fetal karyotyping is advisable.
Figure 2. Fetal ultrasound of duodenal atresia at 20 weeks gestation showing 'double-bubble' appearance of gastric and duodenal dilatation.
Approximately 55% of infants with duodenal atresia were diagnosed prenatally in South East Thames between 1992 and 1995. Surprisingly, only I case was terminated in this series and the majority of live-born infants were alive at 1 year of age.
Anorectal atresia Anomalies of the hindgut are much more difficult to diagnose prenatally than those of the foregut. Obstruction of the colon, rectum or anus leads to some colonic distension, but this will not usually become apparent until late in gestation, by which time routine antenatal scans are complete. Of 79 confirmed cases of anorectal atresia reported to the South East Thames Congenital Malformation Registry, none was identified or suspected before birth (Table 1). The observation of fetal hydronephrosis in association with intestinal dilatation may provide a clue for the astute sonographer, since anorectal malformations are frequently associated with urological abnormalities, particularly vesico-ureteric reflux [10]. Anorectal malformation is also a component of the VACTERL syndrome [10], and should be considered in fetuses presenting with other visceral abnormalities, including suspected oesophageal atresia.
Exomphalos In exomphalos, the abdominal wall defect is situated in the midline around the point of insertion of
Impact of Prenatal Diagnosis on Neonatal Surgery
the umbilical cord and is covered by a membranous sac similar in constitution t o the coverings of the cord. The intraperitoneal viscera, predominantly liver and intestine, herniate to a greater or lesser degree and are readily visible in the fetus sonographically. Some idea of the operative difficulty which is likely to be encountered in the postnatal closure of the defect may be gained by comparison of the sonographic measurements of the fetal abdominal cavity and the dimensions of the hernial saC.
Additional abnormalities are common in association with exomphalos [11-14] and whenever this condition is identified or suspected prenatally, an immediate and detailed sonographic search for other structural malformations should be undertaken. Cardiac, renal and chromosome abnormalities are particularly common and often dictate an adverse outcome; fetal cardiac scan and karyotyping are required in all cases in order to provide information regarding prognosis. Nowadays, the majority of cases with multiple abnormalities are terminated, and consequently the outlook for liveborn infants with isolated exomphalos is much improved (Table 1). The size of the sac alone should not be considered an indication for termination, since small infants with a large defect have been successfully closed on many occasions. While delivery in a neonatal surgical centre may facilitate surgical planning, infants with isolated exomphalos may be delivered locally and transferred for surgery without hazard, provided the covering sac remains protected and intact.
Gastroschisis The abdominal wall defect in gastroschisis is usually small and situated to the right side of the insertion of the cord. In this abnormality there is no covering sac and on fetal sonography, the herniated viscera can be seen floating freely in the amniotic cavity. The sonographic appearances of gastroschisis vary depending on the gestational age and the condition of the extruded bowel. On early scans (before 16 weeks) the bowel may appear as a small bunch of grape-like cysts close to the insertion of the cord. Later in gestation, the loops of bowel may become more prominent as they dilate due to partial obstruction of the lumen by the sides of the defect. Thickening of the bowel wall may be observed on serial scans [15], and more
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severe complications such as volvulus, atresia and ischaemia may result in massive dilatation. Associated malformations are much less common in gastroschisis than in exomphalos and chromosomal abnormalities are rare, making fetal karyotyping less important than in exomphalos [14]. Nevertheless, a detailed sonographic examination should be performed, since up to 13% of fetuses with gastroschisis are reported to have abnormalities outwith the gastrointestinal tract [3]. Serial sonography is helpful in gastroschisis [16], primarily to give the surgical team early warning of possible atresia or other intestinal complications which may be difficult to identify in matted bowel at operation. Intestinal obstruction secondary to atresia or luminal constriction by the edges of the defect may result in polyhydramnios; preterm labour in such circumstances is not uncommon and parents should be warned of this possibility. The majority of infants with gastroschisis are identified prenatally (Table 1) and few are terminated. Regardless of the sonographic appearances, there are few if any advantages in elective preterm delivery or caesarean section. In-utero transfer and delivery in a neonatal surgical centre is likely to be advantageous in reducing perinatal morbidity, although many deliveries planned for 37 weeks are overtaken by spontaneous labour at an earlier stage. Survival for live-born infants is good; mortality is usually related to complications arising from long-term parenteral nutrition required for prolonged ileus or short bowel syndrome secondary to intestinal ischaemia.
Bladder and cloacal exstrophy Bladder exstrophy is rare and cloacal exstrophy even rarer [17, 18]. In the normal fetus, bladder development takes place between the 5th and 9th weeks of gestation [19] and the bladder should be visible as a fluid filled sac by the end of the first trimester. Cloaca[ exstrophy is accompanied by exomphalos in 90% cases [18]; it is the latter defect which is likely to command sonographic attention and the bladder and hindgut anomaly may go undetected if detailed evaluation of the pelvic organs is overlooked. In all suspected cases of exomphalos, the presence of a normal bladder should be documented. Structural abnormalities of the upper urinary tract and other systems are common in association with cloacaI exstrophy (75-95% cases) [18] but are uncommon in isolated
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Figure 3. Fetal ultrasound at 17 weeks gestation showing grossly dilated bladder and oligohydramnMs due to posterior urethral valves.
bladder exstrophy [20]; karyotype anomalies are rare in both conditions. Only 5 cases of bladder exstrophy and none of cloacal exstrophy were reported in South East Thames between 1992 and 1995 (Table 1). Since optimal outcome in both anomalies demands immediate postnatal assessment and a complex longterm programme of surgery, prenatal diagnosis and parental counselling are highly desirable, but regrettably few cases have been identified before birth (Table 1). Failure to visualize the bladder at the time of a routine second trimester antenatal scan (14-16 weeks) should alert sonographers to the possibility of exstrophy. As pregnancy progresses, failure to have visualized the bladder at any time must be a cause for concern. Any prenatal suspicion of bladder or cloacal exstrophy should trigger immediate consultation with a multidisciplinary specialist team including paediatric surgeons and urologists, a full sonographic fetal structural survey and detailed parental counselling.
Posterior urethral valves Lower urinary tract obstruction in males is most commonly due to posterior urethral valves and may be detected sonographically in the fetus from early in the second trimester [21]. Signs suggestive of urethral obstruction are a large, thick-walled bladder which does not empty and oligohydramnios (Fig. 3). Posterior urethral dilatation may be seen and bilateral hydronephrosis may be present. In severe cases of complete obstruction however,
E. H. Dykes & R. M. Fisher
the kidneys may be small and dysplastic; the absence of fetal hydronephrosis does not exclude obstruction. The prognosis in posterior-urethral valves is dependent on renal and pulmonary function after birth. Although several techniques have been developed for bypassing the urethral obstruction in utero [21], there is little, if any, evidence that the long-term outcome is altered. If a fetal obstructive uropathy is identified, multidisciplinary counselling involving a paediatric surgeon or urologist should be offered immediately. In many cases the outlook is so poor that parents may opt for termination. Discussion of the various options for fetal surgical intervention (e.g. vesico-amniotic shunt) should emphasize that, while this may improve the short-term outcome and allow lung maturation, the benefits on longterm renal function are not clear. It should not be forgotten that the child with posterior urethral valves usually also has significant bladder damage which may require complicated surgery and intermittent self-catheterization to achieve continence. The early and accurate diagnosis of this condition is important in allowing parents the greatest number of options. Between 1992 and 1995, 41 cases of posterior urethral valves were reported in South East Thames (Table 1). Only two cases were precisely diagnosed prenatally, but a further 33 were suspected on the basis of bilateral hydronephrosis and a large bladder in male fetuses. Although 95% of live-born infants were alive at 1 year, longer follow-up is necessary before the real effects of early diagnosis and intervention can be assessed.
Spina bifida Perhaps the earliest structural abnormality to be identified prenatally, and previously one of the most common, is spina bifida with associated myelomeningocoele. Recent reports suggest that the overall incidence of this condition is decreasing, but whether this is a result of improved maternal nutrition or other factors is not clear [22]. In South East Thames only 77 cases were identified over a 3-year period (Table 1), of which 61 (79%) were prenatally diagnosed and 5.5 (90% of prenatal diagnoses) were terminated. Only 7 cases (the majority with minor defects) were live-born, and all survived to one year of age. As a consequence of this decreasing clinical incidence, postnatal
Impact of Prenatal Diagnosis on Neonatal Surgery
experience of this condition is decreasing; referral to a multidisciplinary specialist unit is essential if optimal long-term function is to be achieved.
Conclusions Prenatal diagnosis affords opportunities for delineation of the defect, parental counselling and intervention in the pregnancy, as well as providing time in which to plan optimal perinatal management of surgically correctable malformations. The role of in-utero surgical intervention is controversial. Dramatic reports of success in various surgical conditions including diaphragmatic hernia, cystic adenomatoid malformation, obstructive uropathy and spina bifida receive much media attention, but the risks to the mother (and fetus) should not be underestimated. Careful case selection is required and one of the current problems is a lack of consensus on the criteria which would justify in-utero surgery. Additionally, in most conditions, intervention would need to be undertaken at a prohibitively early stage of gestation to have any significant effect on outcome, with the correspondingly increased risk of preterm labour. Nevertheless, the technology is now available and offers a valuable tool for experimental studies of fetal and maternal physiology [23]. Prenatal diagnosis also affects the clinical prevalence and outcome of some conditions, often as a result of selective termination of those with lethal or multiple anomalies, but doubtless also as a result of the planned perinatal care which occurs. An appreciation of the accuracy of prenatal diagnosis is dependent on population based studies and reliable follow-up, including postmortem examination of spontaneous and therapeutic abortions. Neonatal surgeons should be informed of any prenatal diagnosis of a surgical abnormality and should be actively involved as part of a multidisciplinary team in parental counselling and perinatal management.
Acknowledgements The South East Thames Congenital Malformation Registry is funded by the South Thames Regional Health Authority. The authors wish to thank Ms Ann Partington (Registry Co-ordinator) and all reporting specialists and units in the South Thames (east) Region for their contributions to the collection of data reported in this paper.
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References 1 Northern Regional Survey Steering Group. Fetal abnormality; an audit of its recognition and management. Arch Dis Child 1992; 67: 770-774. 2 Owens JR, Simpkin JM, McGuinness L e t al. The Liverpool Congenital Malformation Register. Paediatr Perinat Epidemiol 1988; 21: 240-252. 3 Fisher R, Attah A, Partington A et al. Impact of antenatal diagnosis on incidence and prognosis in abdominal wall defects. ] Pediatr Surg 1996; 31: 538-541. 4 Harrison MR. The fetus with a diaphragmatic hernia: pathophysiology, natural history and surgical management. In: Harrison MR, Golbus MS, Filly RA (eds) Tlle Unborn Patient. Philadelphia: W.B. Saunders, 1990; 295313. 5 Sweed Y, Purl P. Congenital diaphragmatic hernia: influence of associated malformations on survival. Arch Dis Child 1993; 69: 68-70. 6 McCullagh M, McConnachie I, Garvie D et al. Accuracy of prenatal diagnosis of congenital cystic adenomatoid malformation. Arch Dis Child 1994; 71: FIll-F113. 7 Nishibayashi SW, Andrassy RJ, Woolley MM. Congenital cystic adenomatoid malformation: a 30 year experience. ] Pedialr Surg 1981; 16: 704-706. 8 Spitz L, Hitchcock RJ. Oesophageal atresia and tracheooesophageal fistula. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) Surgend of the Newborn. London: Churchill Livingstone, 1994; 353-373. 9 Menardi G. Duodenal atresia, stenosis and annular pancreas. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) Surgery of tlle Newborn. London: Churchill Livingstone, 1994; I07-115. 10 Freeman NV. Anorectal malformations. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) Surgeny of the Nezoborn. London: Churchill Livingstone, 1994; 171-199. 11 Moore TC, Nur K. An international survey of gastroschisis and omphalocoele (490 cases). I: Nature and distribution of additional malformations. Pediatr Surg h# 1986; 1: 46-50. 12 Gilbert WM, Nicolaides KH. Fetal omphalocoele: associated malformations and chromosomal defects. Obstet Gynecol 1987; 70: 633-635. 13 Nicolaides KH, Snijders RJM, Cheng HH et al. Fetal gastrointestinal and abdominal wall defects: associated malformations and chromosomal abnormalities. Fetal Diagn Tiler 1992; 7: 102-115. 14 Bax NMA. Exomphalos and gastroschisis. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) Surgery of tile l\¥zoborn. London: Churchill Livingstone, 1994; 301-320. 15 Langer JC, kongaker MT, Crombleholme TM et al. Etiology of bowel damage in gastroschisis. I: Effects of amniotic fluid exposure and bowel constriction in a fetal lamb model. ] Pediatr Surg 1989; 24: 992-997. 16 Langer JC, Khanna J, Caco C et al. Prenatal diagnosis of gastroschisis: development of objective sonographic criteria for predicting outcome. Obstet Gynecol 1993; 81: 53-56. 17 International Clearinghouse for Birth Defects Monitoring Systems. Epidemiology of bladder exstrophy and epispadias. Teralology I987; 36: 221-227.
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18 Manzoni GM, Hunvitz RS. Cloacal exstrophy. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) S~,rgery of the Newborn. London: Churchill Livingstone, 1994; 767-780. 19 Arey LB. The Urinary System in DevelopmentalAnatomy. A Textbook and Laboratory Mammal of Embryology, 7th edn (revised). Philadelphia: W.B. Saunders, 1974; 295-314. 20 Malone PS. Bladder exstrophy and epispadias complex. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) Surgery of the Newborn. London: Churchill Livingstone, 1994; 75.5-765.
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2/ Ahmed S, Crankson SJ. Lower urinary tract obstruction. In: Freeman NV, Burge DM, Griffiths DM, Malone PSJ (eds) Surgery of the Newborn. London: Churchill Livingstone, 1994; 707-728. 22 EUROCAT Working Group. Prevalence of neural tube defects in twenty regions of Europe and the impact of prenatal diagnosis 1980-1986. ] Epidenliol Community Health 1991; 45: 52-58. 23 Harrison MR, Adzick NS. Fetal surgical techniques. Semin Pediatr Surg 1993; 2: 136-142.
Impact of prenatal diagnosis on neonatal surgery Evelyn H. Dykes and Ross M. Fisher
South East Thames Congenital Malformation Registry, Children's Hospital, Lewisham, London, UK
Key words: prenatal diagnosis, ultrasound, neonatal surgery, congenital abnormality
Prenatal ultrasound diagnosis has radically altered neonatal surgical practice. Advance warning of severe structural malformations allows time for detailed parental counselling by neonatal surgeons in conjunction with obstetricians and neonatologists, so that the parents of an infant with an abnormality may be adequately prepared for the investigations and surgery which will be required after birth. Prenatal diagnosis also creates opportunities for interventions during pregnancy such as fetal karyotyping, in-utero transfer and planned delivery in a perinatal centre where neonatal surgical and anaesthetic expertise is readily available. Selective termination of fetuses found to have chromosomal abnormalities or such severe abnormalities that survival is unlikely, results in relatively 'good-risk' populations presenting to neonatal surgeons after birth. Consequently, survival rates after surgery have improved in many conditions. Neonatal surgeons should be informed of any prenatal diagnosis of a surgical abnormality and should be actively involved in parental counselling and perinatal management.
Introduction The increasing use of high resolution fetal sonography in routine antenatal care or as an adjunct following demonstration of raised maternal serum c~-fetoprotein has resulted in the early identification of many surgically correctable fetal malformations. Advance warning of these conditions has radically altered neonatal surgical practice with respect to parental information, patient populations and outcome after surgery. In the past, neonatal surgeons only became aware of an infant with an abnormality after delivery. In most cases the baby was delivered in a district hospital, necessitating an urgent transfer to the neonatal surgical centre for assessment and surgery. In many instances the parents, particularly the mother, were unable to accompany the baby and often did not meet the surgeon until any urgent surgery was completed. In some tragic situations, notably diaphragmatic hernia, the baby died before specialist surgical consultation could be obtained. Correspondence:E.H.Dykes,Departmentof PaediatricSurgery.Children's ttospital. Lewisham.LondonSE136LILUK. 1084-2756/96/030177+ 08 $12.00/00
Nowadays it is unusual for such unsatisfactory situations to occur. The majority of severe structural malformations are identified before birth and in optimal circumstances, the parents will have met a neonatal surgeon at an early stage of the pregnancy to discuss the nature of the malformation, postnatal management (including investigations and surgery) and likely outcome, taking into account factors such as chromosome abnormalities or multiple anomalies. Furthermore, for infants with malformations which may require immediate or urgent surgery, arrangements for planned delivery in a neonatal surgical centre can be made well in advance, permitting optimal perinatal management as well as parental presence throughout. Contingency plans for unexpected preterm labour can also be made and discussed with the local obstetricians and paediatricians. Good communication throughout is paramount, since, if the best outcome for the infant and family is to be achieved, all clinicians involved (including the general practitioner, local obstetrician and local neonatologist, as well as fetal medicine specialists, neonatologists and surgeons in the tertiary centre) must be kept informed of any decisions. Parents of © 1996 W.B. Saunders Company Ltd
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a baby with a surgical condition requiring neonatal intensive care often find it helpful to visit the perinatal centre in advance of the birth to familiarize themselves with the location, layout and staff of the unit concerned. Perhaps the most important factor in planning the optimal neonatal surgical care of an infant with a prenatally-diagnosed surgical malformation is a knowledge of the likely accuracy of the prenatal diagnosis. Inevitably this varies, depending on the condition and organ system in question and on the expertise and experience of the sonographer. It is essential that all fetuses with a suspected surgical anomaly are referred to a specialist fetal medicine unit for confirmation and most such units incorporate multidisciplinary diagnostic and counselling facilities. Even there however, a specific diagnosis may not be assured. Appreciation of the limitations of prenatal diagnosis is important for both clinicians and parents. In order to evaluate the accuracy and impact of prenatal ultrasound diagnosis, a number of population-based registries have been established [1-3]. The benefit of such registries is that they do not rely on single centre reports which, although valuable, do not reflect the experience of the population as a whole. Data on interventions and outcomes of each pregnancy are also held by registries. Knowledge of local prenatal diagnostic accuracy rates and outcomes for different malformations gives an up-to-date perspective on the current status of prenatal diagnosis and provides important information for those involved in counselling and postnatal care. The data reported below are derived from the experience of the South East Thames Congenital Malformation Registry from I992-I995 and reflect the impact of prenatal diagnosis in selected surgical conditions based on a population of 3.5 million with an annual birth rate of 52 000.
South East Thames Congenital Malformation Registry The South East Thames Congenital Malformation Registry was established in April 1992 as the result of an initiative supported by the Regional Medical Audit Committee. Notification of all identified cases of major congenital structural abnormalities diagnosed pre- or postnatally is requested from all obstetric, fetal medicine, paediatric and pathology
E. H. Dykes & R. M. Fisher
Figure 1. Fetal ultrasound of diaphragmatic hernia at 18 weeks gestation showing the stomach next to the heart which is shifted to the right side.
units in the region. Once notified of a case, the registry co-ordinator collects data on the time and method of diagnosis, any prenatal interventions, time and place of delivery, nature of abnormalities and ultimate outcome up to I year after birth. All data are collected and maintained according to the regulations of the Data Protection Act (1994).
Prenatal diagnosis of selected neonatal surgical abnormalities Congenital diaphragmatic hernia Congenital diaphragmatic hernia remains one of the commonest and most controversial surgical abnormalities. Prenatal diagnosis is based on visualization of the fetal stomach above the diaphragm beside the heart, often in association with demonstrabte fetal lung hypoplasia and mediastinal shift (Fig. 1). Polyhydramnios may be present (possibly as a result of impaired fetal swallowing secondary to oesophageal compression) and part of the liver may also be seen within the chest. It was previously held that infants with a prenatal diagnosis of a congenital diaphragmatic hernia had a poorer prognosis than those not identified prenatally [4]. However, recent experience suggests that prenatal diagnosis may not alter the outcome; data from the South East Thames Congenital Malformation Registry shows that the 1-year survival rate for the 43 infants with prenatally diagnosed diaphragmatic hernia equalled that for the 16 with unsuspected lesions (69.8%
Impact of Prenatal Diagnosis on Neonatal Surgery
179
Table 1. Prenatal diagnosis and outcome in selected surgical malformations reported to South East Thames Congenital Malformation Registry during a three year period (1992-1995) Malformation
Diaphragmatic hernia Cystic lung lesions Oesophageal atresia Duodenal atresia AnorectaI atresia Exomphalos Gastroschisis Bladder exstrophy Posterior urethral valves Myelomeningocoele
Confirmed cases
73 21 43 20 79 40 40 5 41 77
Prenatal diagnoses (%)
52 19 6 11 0 39 38 2 35 61
(71) (90) (14) (55) (0) (98) (95) (40) (85) (79)
versus 68.7%), while for isolated diaphragmatic hernias (n=49), 1-year survival in the prenatally diagnosed group was 79% compared with 73% for infants with unsuspected hernias. Gestational age at diagnosis does not appear to be relevant to outcome; there was no difference between survivors and deaths in this respect. Approximately 30% of infants in each group were diagnosed before 20 weeks gestation. It is likely that more refined prenatal diagnosis contributes to a greater proportion of cases being identified prenatally, with the result that earlier apparent differences in outcome are now insignificant. However, in view of the significant incidence of associated malformations (particularly cardiac) which may adversely affect survival [5] a careful prenatal search for other abnormalities is essential. In infants with multiple anomalies, the prognosis may be so poor that the parents opt for termination of the pregriancy. Consequently, fetuses surviving to delivery may be a selected 'low-risk' group, whose survival depends entirely on the degree of lung hypoplasia and may in fact be better than that seen previously in 'all-comers' (Table 1). Additionally, prenatal diagnosis permits optimal planning of delivery and neonatal resuscitation, which may independently improve survival.
Cystic abnormalities of the lung Congenital cystic abnormalities of the lung include cystic adenomatoid malformations, isolated lung cysts and pulmonary sequestrations. Although it is possible to demonstrate cysts within the fetal lung
Terminated
I1 2 4 1 17 23 2 2 3 55
Live-born (%)
59 18 38 16 50 14 34 3 38 7
(81) (86) (88) (80) (63) (35) (85) (60) (93) (9)
Alive at I year (% live births)
41 (70) 17 (94) 34 (89) 15 (94) 47 (94) 11 (79) 33 (97) 3 (100) 36 (95) 7 (100)
on sonography, it is rarely possible to be specific about a precise diagnosis prenatally [6]. Persistent large lesions causing mediastinal shift are most likely to require urgent neonatal surgery, but even in such cases the clinical symptoms after delivery may be mild. A significant proportion of prenatally diagnosed lung cysts regress during pregnancy and some have been seen to disappear completely [6]. Consequently, caution is required when making a prognosis on such anomalies prenatally. If a cystic lung abnormality is detected, serial scans are helpful in following the progression of the lesion. Those which persist to delivery will require further investigation, and the need for surgical removal must be considered. Of 21 confirmed cystic lung lesions identified from the South East Thames Congenital Malformation Registry during a 3-year period, 19 (90%) were identified prenatally and 17 (94% of live births) were alive at one year of age (Table 1). These results suggest that the spectrum of disease being identified prenatally is wide and is likely to include minor malformations which might previously have remained undiagnosed. Certainly the symptoms in this group are significantly different from those reported in previous studies of postnatally identified congenital cystic adenomatoid malformation (CCAM) [7]; in our experience, most infants with prenatally diagnosed CCAM have no symptoms at birth and may in fact have normal chest X-rays for several months. A previous report has highlighted the difficulties in distinguishing between CCAM and other cystic lung lesions in the fetus [6]; caution should be exercised when making precise prenatal diagnoses in such malformations.
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Oesophageal atresia Oesophageal atresia results in impaired swallowing of amniotic fluid by the fetus, and consequently may give rise to polyhydramnios. Sonographic demonstration of the fetal oesophagus is difficult if not impossible, and the diagnosis is usually made on circumstantial evidence. In some cases (without a tracheo-oesophageal fistula) absence of the normally visible fetal stomach in the presence of polyhydramnios may raise the possibility of an atresia. However, since the most common form of oesophageal atresia is associated with a fistula between the trachea and the distal oesophagus [8], fetal breathing movements may allow amniotic fluid to pass into the stomach, which thus appears sonographically normal. It is not surprising therefore, that currently, the majority of oesophageal atresias remain undetected until after delivery (Table 1). In cases suspected prenatally, it is wise to consult the local neonatal surgical centre, since urgent surgery is likely to be required (particularly in cases with an associated fistula to the trachea), and delivery at a perinatal centre may be advised. Oesophageal atresia is often associated with other malformations [8], and a prenatal sonographic search for anomalies of the heart, skeleton and kidneys is essential. Chromosome abnormalities are infrequent (approximately 10%) but if oesophageal atresia is suspected, fetal karyotyping may be helpful for prognostic purposes.
Duodenal obstruction Duodenal obstruction may be caused by atresia, stenosis, annular pancreas or malrotation. In the fetus, duodenal obstruction results in distension of the stomach with secondary polyhydramnios; it is rarely possible to distinguish the cause of the obstruction prenatally. Occasionally the characteristic postnatal double-bubble' sign is seen sonographically (Fig. 2). The commonest malformation is duodenal atresia, which is associated with Down's syndrome in 30% of patients [9]. The presence of polyhydramnios in association with other sonographic markers of karyotype abnormality may lead to a suspicion of duodenal atresia; conversely, a diagnosis of fetal duodenal obstruction should trigger a sonographic search for other markers of chromosome anomaly and fetal karyotyping is advisable.
Figure 2. Fetal ultrasound of duodenal atresia at 20 weeks gestation showing 'double-bubble' appearance of gastric and duodenal dilatation.
Approximately 55% of infants with duodenal atresia were diagnosed prenatally in South East Thames between 1992 and 1995. Surprisingly, only I case was terminated in this series and the majority of live-born infants were alive at 1 year of age.
Anorectal atresia Anomalies of the hindgut are much more difficult to diagnose prenatally than those of the foregut. Obstruction of the colon, rectum or anus leads to some colonic distension, but this will not usually become apparent until late in gestation, by which time routine antenatal scans are complete. Of 79 confirmed cases of anorectal atresia reported to the South East Thames Congenital Malformation Registry, none was identified or suspected before birth (Table 1). The observation of fetal hydronephrosis in association with intestinal dilatation may provide a clue for the astute sonographer, since anorectal malformations are frequently associated with urological abnormalities, particularly vesico-ureteric reflux [10]. Anorectal malformation is also a component of the VACTERL syndrome [10], and should be considered in fetuses presenting with other visceral abnormalities, including suspected oesophageal atresia.
Exomphalos In exomphalos, the abdominal wall defect is situated in the midline around the point of insertion of
Impact of Prenatal Diagnosis on Neonatal Surgery
the umbilical cord and is covered by a membranous sac similar in constitution t o the coverings of the cord. The intraperitoneal viscera, predominantly liver and intestine, herniate to a greater or lesser degree and are readily visible in the fetus sonographically. Some idea of the operative difficulty which is likely to be encountered in the postnatal closure of the defect may be gained by comparison of the sonographic measurements of the fetal abdominal cavity and the dimensions of the hernial saC.
Additional abnormalities are common in association with exomphalos [11-14] and whenever this condition is identified or suspected prenatally, an immediate and detailed sonographic search for other structural malformations should be undertaken. Cardiac, renal and chromosome abnormalities are particularly common and often dictate an adverse outcome; fetal cardiac scan and karyotyping are required in all cases in order to provide information regarding prognosis. Nowadays, the majority of cases with multiple abnormalities are terminated, and consequently the outlook for liveborn infants with isolated exomphalos is much improved (Table 1). The size of the sac alone should not be considered an indication for termination, since small infants with a large defect have been successfully closed on many occasions. While delivery in a neonatal surgical centre may facilitate surgical planning, infants with isolated exomphalos may be delivered locally and transferred for surgery without hazard, provided the covering sac remains protected and intact.
Gastroschisis The abdominal wall defect in gastroschisis is usually small and situated to the right side of the insertion of the cord. In this abnormality there is no covering sac and on fetal sonography, the herniated viscera can be seen floating freely in the amniotic cavity. The sonographic appearances of gastroschisis vary depending on the gestational age and the condition of the extruded bowel. On early scans (before 16 weeks) the bowel may appear as a small bunch of grape-like cysts close to the insertion of the cord. Later in gestation, the loops of bowel may become more prominent as they dilate due to partial obstruction of the lumen by the sides of the defect. Thickening of the bowel wall may be observed on serial scans [15], and more
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severe complications such as volvulus, atresia and ischaemia may result in massive dilatation. Associated malformations are much less common in gastroschisis than in exomphalos and chromosomal abnormalities are rare, making fetal karyotyping less important than in exomphalos [14]. Nevertheless, a detailed sonographic examination should be performed, since up to 13% of fetuses with gastroschisis are reported to have abnormalities outwith the gastrointestinal tract [3]. Serial sonography is helpful in gastroschisis [16], primarily to give the surgical team early warning of possible atresia or other intestinal complications which may be difficult to identify in matted bowel at operation. Intestinal obstruction secondary to atresia or luminal constriction by the edges of the defect may result in polyhydramnios; preterm labour in such circumstances is not uncommon and parents should be warned of this possibility. The majority of infants with gastroschisis are identified prenatally (Table 1) and few are terminated. Regardless of the sonographic appearances, there are few if any advantages in elective preterm delivery or caesarean section. In-utero transfer and delivery in a neonatal surgical centre is likely to be advantageous in reducing perinatal morbidity, although many deliveries planned for 37 weeks are overtaken by spontaneous labour at an earlier stage. Survival for live-born infants is good; mortality is usually related to complications arising from long-term parenteral nutrition required for prolonged ileus or short bowel syndrome secondary to intestinal ischaemia.
Bladder and cloacal exstrophy Bladder exstrophy is rare and cloacal exstrophy even rarer [17, 18]. In the normal fetus, bladder development takes place between the 5th and 9th weeks of gestation [19] and the bladder should be visible as a fluid filled sac by the end of the first trimester. Cloaca[ exstrophy is accompanied by exomphalos in 90% cases [18]; it is the latter defect which is likely to command sonographic attention and the bladder and hindgut anomaly may go undetected if detailed evaluation of the pelvic organs is overlooked. In all suspected cases of exomphalos, the presence of a normal bladder should be documented. Structural abnormalities of the upper urinary tract and other systems are common in association with cloacaI exstrophy (75-95% cases) [18] but are uncommon in isolated
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Figure 3. Fetal ultrasound at 17 weeks gestation showing grossly dilated bladder and oligohydramnMs due to posterior urethral valves.
bladder exstrophy [20]; karyotype anomalies are rare in both conditions. Only 5 cases of bladder exstrophy and none of cloacal exstrophy were reported in South East Thames between 1992 and 1995 (Table 1). Since optimal outcome in both anomalies demands immediate postnatal assessment and a complex longterm programme of surgery, prenatal diagnosis and parental counselling are highly desirable, but regrettably few cases have been identified before birth (Table 1). Failure to visualize the bladder at the time of a routine second trimester antenatal scan (14-16 weeks) should alert sonographers to the possibility of exstrophy. As pregnancy progresses, failure to have visualized the bladder at any time must be a cause for concern. Any prenatal suspicion of bladder or cloacal exstrophy should trigger immediate consultation with a multidisciplinary specialist team including paediatric surgeons and urologists, a full sonographic fetal structural survey and detailed parental counselling.
Posterior urethral valves Lower urinary tract obstruction in males is most commonly due to posterior urethral valves and may be detected sonographically in the fetus from early in the second trimester [21]. Signs suggestive of urethral obstruction are a large, thick-walled bladder which does not empty and oligohydramnios (Fig. 3). Posterior urethral dilatation may be seen and bilateral hydronephrosis may be present. In severe cases of complete obstruction however,
E. H. Dykes & R. M. Fisher
the kidneys may be small and dysplastic; the absence of fetal hydronephrosis does not exclude obstruction. The prognosis in posterior-urethral valves is dependent on renal and pulmonary function after birth. Although several techniques have been developed for bypassing the urethral obstruction in utero [21], there is little, if any, evidence that the long-term outcome is altered. If a fetal obstructive uropathy is identified, multidisciplinary counselling involving a paediatric surgeon or urologist should be offered immediately. In many cases the outlook is so poor that parents may opt for termination. Discussion of the various options for fetal surgical intervention (e.g. vesico-amniotic shunt) should emphasize that, while this may improve the short-term outcome and allow lung maturation, the benefits on longterm renal function are not clear. It should not be forgotten that the child with posterior urethral valves usually also has significant bladder damage which may require complicated surgery and intermittent self-catheterization to achieve continence. The early and accurate diagnosis of this condition is important in allowing parents the greatest number of options. Between 1992 and 1995, 41 cases of posterior urethral valves were reported in South East Thames (Table 1). Only two cases were precisely diagnosed prenatally, but a further 33 were suspected on the basis of bilateral hydronephrosis and a large bladder in male fetuses. Although 95% of live-born infants were alive at 1 year, longer follow-up is necessary before the real effects of early diagnosis and intervention can be assessed.
Spina bifida Perhaps the earliest structural abnormality to be identified prenatally, and previously one of the most common, is spina bifida with associated myelomeningocoele. Recent reports suggest that the overall incidence of this condition is decreasing, but whether this is a result of improved maternal nutrition or other factors is not clear [22]. In South East Thames only 77 cases were identified over a 3-year period (Table 1), of which 61 (79%) were prenatally diagnosed and 5.5 (90% of prenatal diagnoses) were terminated. Only 7 cases (the majority with minor defects) were live-born, and all survived to one year of age. As a consequence of this decreasing clinical incidence, postnatal
Impact of Prenatal Diagnosis on Neonatal Surgery
experience of this condition is decreasing; referral to a multidisciplinary specialist unit is essential if optimal long-term function is to be achieved.
Conclusions Prenatal diagnosis affords opportunities for delineation of the defect, parental counselling and intervention in the pregnancy, as well as providing time in which to plan optimal perinatal management of surgically correctable malformations. The role of in-utero surgical intervention is controversial. Dramatic reports of success in various surgical conditions including diaphragmatic hernia, cystic adenomatoid malformation, obstructive uropathy and spina bifida receive much media attention, but the risks to the mother (and fetus) should not be underestimated. Careful case selection is required and one of the current problems is a lack of consensus on the criteria which would justify in-utero surgery. Additionally, in most conditions, intervention would need to be undertaken at a prohibitively early stage of gestation to have any significant effect on outcome, with the correspondingly increased risk of preterm labour. Nevertheless, the technology is now available and offers a valuable tool for experimental studies of fetal and maternal physiology [23]. Prenatal diagnosis also affects the clinical prevalence and outcome of some conditions, often as a result of selective termination of those with lethal or multiple anomalies, but doubtless also as a result of the planned perinatal care which occurs. An appreciation of the accuracy of prenatal diagnosis is dependent on population based studies and reliable follow-up, including postmortem examination of spontaneous and therapeutic abortions. Neonatal surgeons should be informed of any prenatal diagnosis of a surgical abnormality and should be actively involved as part of a multidisciplinary team in parental counselling and perinatal management.
Acknowledgements The South East Thames Congenital Malformation Registry is funded by the South Thames Regional Health Authority. The authors wish to thank Ms Ann Partington (Registry Co-ordinator) and all reporting specialists and units in the South Thames (east) Region for their contributions to the collection of data reported in this paper.
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