Appropriately Grown Baby With Multiple Congenital Abnormalities: A Case Report

Abstract

We present the case of a full-term baby girl (Baby A) born with multiple congenital abnormalities that were suggested by prenatal scans. The mother had declined further antenatal diagnostic testing. Postnatal chromosomal analyses revealed the karyotype of the baby to be trisomy 18. After detailed, compassionate discussions with the parents, it was decided to provide palliative care in the best interest of the baby, who died on day 15 of life. This case illustrates ethical difficulties in the care of neonates with congenital anomalies with poor prognoses, such as trisomy 18. Recommending palliative care and “do not resuscitate” orders to optimistic parents is extremely difficult and needs to be done in the most sensitive manner possible.

Introduction

Trisomy 18 (Edwards syndrome) is the second most common chromosomal anomaly after Down syndrome, with a prevalence of 1.29 in 10,000 live births. These babies have multiple physical congenital abnormalities. Of the 10% of babies who survive the first year of life, all have mental retardation.

Case Report

Mrs. A is a 37-year-old Somali woman. She had no significant medical or surgical history, took no medications regularly during her pregnancy, and remained well throughout. She does not smoke or drink alcohol and has never abused drugs.

At presentation, she was gravida 11, para 7, with 3 prior miscarriages. Routine laboratory tests showed that she was blood group A, Rhesus-positive. She was negative for syphilis, HIV, and hepatitis B and C and was positive for rubella antibodies.

The fetal anomaly scan at 24⁺⁶ weeks was grossly abnormal: A large irregular cyst in the brain, possible dextrocardia, abnormal great vessels of the heart, and an atrioventricular septal defect were found. The fetus was rescanned at a specialist cardiology unit at 25⁺³ weeks and was found to have a perimembranous ventricular septal defect and dysmorphic atrioventricular valves. Mrs. A. was offered the opportunity for invasive testing considering the high likelihood of a chromosomal or genetic abnormality and future physical and mental handicap. Mrs. A. refused any invasive testing on religious grounds.

Subsequently, Mrs. A underwent further fetal scans at 32⁺⁴, 36⁺⁴, and 39⁺⁴ weeks. At no scan was fetal growth found to be compromised. The scan at 32⁺⁴ weeks revealed a right porencephalic cyst (31.0 mm × 19.0 mm × 15.0 mm), a posterior fossa cyst (13.0 mm × 48.0 mm × 15.0 mm), and a dilated cisterna magna. At this stage, bilateral overlapping fingers were also noted. The stomach was found to be collapsed.

Not having a diagnosis makes it extremely difficult for the pediatrician-in-charge to plan any immediate care for the baby after birth. Mr. and Mrs. A. were counseled by the consultant neonatologist, and it was decided that if the baby was born in poor condition, he/she should not be resuscitated and should instead be given to the mother to cuddle. However, if the baby was crying and well, he/or she should be taken to the neonatal unit for further management.

Because of the unstable lie of the fetus, polyhydramnios, and cord presentation, Baby A was born by elective lower-segment cesarean section at gestation 40⁺³ weeks.

Baby A was a girl, with a birth weight of 3.25 kg (25th percentile), and was born in reasonably good condition. The APGAR scores were 6 at 1 minute, 9 at 5 minutes, and 10 at 10 minutes of age. The cord blood gases were within the normal range. In view of the multiple anomalies, Baby A was transferred to the neonatal unit in a transport incubator.

On examination, Baby A looked pink and well-perfused, was breathing on her own, and had oxygen saturation of 90% to 99% in 60% head box oxygen. Her heart rate was 162 beats per minute, blood pressure was 68/49 mm Hg, and her heart sounds were normal with no added sounds or murmurs. Her respiratory rate was 60 breaths per minute. Her abdomen was soft, nondistended, and nontender. Neurologically, Baby A was active and the anterior fontanel was soft and not bulging.

Baby A's eyes appeared deep set, with narrow palpebral fissures bilaterally. Her mouth was small, with a central notch in the upper gums and an intact palate. Her ears appeared normal. Her neck appeared to be short, and her chest was broad, with widely spaced nipples (Figure 1a). The posterior folds of the neck were excessive. No masses were felt in the abdomen, and genitalia appeared normal. Hip examination was normal. Her fingers were kept closed, with the second and fifth fingers overlapping the third and fourth fingers, respectively (Figure 1b). The fingers were all hyperextendable. The right hand had a single palmar crease. The right foot had a calcaneal valgus deformity (Figure 1c). The toes were abnormal with a short big toe, and partial syndactyly of the second and third toes of the right foot. The characteristic “rocker-bottom” deformity of the feet was also noted (Figure 1d).

Figure 1.

Physical features of Baby A: (a) short neck, broad chest, and widely spaced nipples; (b) characteristic overlapping fingers seen in trisomy 18; (c) calcaneal valgus deformity; (d) rocker-bottom foot.

These photographs have been provided after explicit consent from Baby A's parents.

Baby A received 10% dextrose infusion for 48 hours of life. Nasogastric tube enteral feed was started on day 1, and she was tolerating total enteral feeds by day 3. Intravenous benzylpenicillin and gentamicin were started because of maternal group B Streptococcus combined with the baby's oxygen requirement. Antibiotics were stopped on day 3 as blood cultures remained negative.

On day 2 of life, Baby A was stable with no apneic episodes, and her oxygen requirement was reduced to 24%. Cranial ultrasonography was done and revealed 2 cysts. The cerebellum could not be visualized. A preliminary karyotype by fluorescence in situ hybridization (FISH) on day 3 of life revealed 3 copies of chromosome 18, consistent with Edwards syndrome, and this was confirmed by further chromosome analysis.

Discussion

Trisomy 18 (also known as Edwards syndrome) was first described in 1960 by Edwards and colleagues.[1] Among liveborn children, trisomy 18 is the second most common autosomal trisomy after trisomy 21 (Down syndrome).[2] Pont and coworkers[2] estimated the prevalence of trisomy 18 as 1.29/10,000 live births. Although, there is no racial predilection,[3] females are 3 times more likely to be affected than males. Like Down syndrome, the incidence increases with advancing maternal age. Full trisomy 18 is responsible for 95% of Edwards syndrome cases, and mosaicism and translocations are responsible for the remainder of cases.[4]

Prenatal screening for trisomy 18 between 10 and 13 weeks, using a combination of pregnancy-associated plasma protein A and beta-human chorionic gonadotropin, has a detection rate of 60% and a false-positive rate of 0.1%.[5] Since most cases of Edwards syndrome have characteristic and detectable structural abnormalities, routine prenatal ultrasonography may suggest the possibility that the fetus is affected. Common anomalies in fetuses with Edwards syndrome include persistent abnormal position of fetal fingers (89%), choroid plexus cysts (43%), 2-vessel umbilical cord (40%), cardiac defects (37%), intrauterine growth retardation (29%), omphalocele (20%), neural tube defects (9%), cystic hygroma or lymphangiectasia (14%), abnormalities of amniotic fluid volume (12%), and renal defects (9%). Prenatal diagnosis with amniocentesis testing (at 14 to 16 weeks of gestation) for a chromosomal disorder is 99.5% accurate; with chorionic villus sampling (at 10–13 weeks of gestation) accuracy increases to 96% to 98%.[6]

Advances in prenatal diagnostics have greatly improved the possibility of early detection of chromosomal anomalies. This has allowed an opportunity to plan and thus improve perinatal care but also offers the option to terminate the pregnancy for cases in which the prognosis is likely to be very poor. Therefore, it is important for both healthcare providers and families to have accurate and detailed knowledge of survival, disease course, and quality of life so that they can make fully informed decisions regarding care.

Patients with Edwards syndrome usually have abnormalities of most body systems and organs (Table). Abnormalities may include growth deficiency, feeding and breathing difficulties, developmental delays, and mental retardation. Various gastrointestinal and genitourinary tract abnormalities have also been described.[4,7]

Table.

Various Documented Abnormalities Associated With Edwards Syndrome

Neurologic	Apnea; microencephaly/anencephaly/hydrocephaly/holoprosencephaly; cerebellar hypoplasia; meningocephalocele/myelomeningocele; Arnold-Chiari malformation; arachnoid cyst; hypoplasia/aplasia of the corpus callosum
Craniofacial	Microphthalmia; ocular hypertelorism; epicanthal folds; short palpebral fissures; cataracts; corneal clouding; abnormal retinal pigmentation; short, upturned nose; choanal atresia; micrognathia; microstomia; infrequent cleft lip; cleft palate; preauricular tags; low-set and malformed ears
Skeletal	Clenched hands with the index finger overriding the middle finger and the fifth finger overriding the fourth finger; radial hypoplasia or aplasia; thumb aplasia; syndactyly of the second and third digits; rocker-bottom feet; talipes equinovarus; short neck with excessive skin folds and short sternum
Cardiac	Ventricular septal defects; pulmonary or aortic valve defects; atrial septal defects; patent ductus arteriosus; overriding aorta; coarctation of aorta; hypoplastic left heart syndrome; tetralogy of Fallot; transposition of great arteries

Definitive diagnosis of Edwards syndrome is by detection of a complete or partial trisomy of chromosome 18 using conventional cytogenetic studies. However, chromosomal analysis can be done using FISH, which gives a rapid provisional result. Various physical anomalies can be confirmed and investigated further using echocardiography, magnetic resonance imaging for cranial anomalies, barium studies for gastrointestinal anomalies, ultrasonography for genitourinary anomalies, and skeletal radiography for skeletal anomalies.[4]

The natural history of Edwards syndrome is one of limited survival. Approximately 68% of the fetuses with an in utero diagnosis of trisomy 18 die before delivery,[7] 30% die in the first month, 50% die within 2 months, and 90% by 1 year.[8] The remaining 10% are mentally retarded.[8] The high mortality rate is usually due to the presence of cardiac and renal malformations, feeding difficulties, sepsis, and apnea caused by CNS defects.[4]

When a diagnosis is confirmed, a detailed discussion with the parents is essential. It is likely to be a difficult time for them, and they will require social support and counseling, including a risk assessment for future pregnancies.

Several ethical issues arise when Edwards syndrome and other serious congenital anomalies are discussed. The issue of the child's best interest is probably the most important. Only 10% of children survive beyond 1 year of life, and they are all mentally retarded, usually with serious physical disabilities. Is surgery for cardiac deformities ethical when it will not change the ultimate prognosis? The answer to the question is probably not, since the surgery is not likely to improve the child's quality of life. In practice, however, the situation is extremely difficult to deal with. Ideally, decisions should result from a joint partnership between parents and healthcare staff.

The other issue that arises is a consideration of the economics of care in determining life and death issues. It is true that health care resources are limited and have to be considered on a social level. Economic considerations include costs to the health service, the parents, social services, and society in general. However, although economic considerations are important, they should not be the main driving force behind decision-making on whether to institute medical treatment.[9]

The statistics and ethical arguments help to explain why treatment for patients with this syndrome is invariably palliative and focuses on quality of life for the infant. Infections are treated appropriately, nasogastric tubes or gastrostomies are used for improved nutrition when required, cardiac abnormalities are treated medically, and referrals are made when necessary to physiotherapists and occupational health workers.[3,4]

Conclusion

After an extensive discussion with Baby A's parents, it was decided that it was not in the baby's best interest to be resuscitated because of the extremely poor long-term prognosis. The medical team and the parents agreed to continue to provide facial oxygen.

Baby A received full palliative care, and her family received social support. Baby A died on day 15 of life. The parents provided informed written consent for publication of this case report.