Congenital paraplegia. A complication of multifetal pregnancy reduction?

BJOG: an International Journal of Obstetrics and Gynaecology May 2002, Vol. 109, pp. 582– 584

CASE REPORT

Congenital paraplegia. A complication of multifetal pregnancy reduction? Mary Paradisisa, William Tarnow-Mordia, Neil Athaydea, Nadia Badawib,* Case report A 31 year old woman was admitted to a tertiary level perinatal centre in preterm labour at 26 weeks of gestation. This was an in vitro fertilisation pregnancy following an eight-year history of infertility. At implantation there were four viable conceptuses. At ten weeks of gestation there had been an attempt at multifetal pregnancy reduction, with the aim of reducing the quadruplet pregnancy to a twin pregnancy. Both the in vitro fertilisation and selective reduction procedures had been performed overseas, and it was not possible to obtain further details of these. Her first local antenatal visit was at 14 –15 weeks of gestation. Ultrasonography at that time recorded the presence of three viable fetuses and one non-viable fetus who appeared anencephalic. Ultrasound examinations at 22 and 25 weeks of gestation showed that one of the three viable fetuses had oedema and talipes of both feet. It is presumed the fourth fetus with anencephaly had been resorbed. Following the onset of spontaneous preterm labour at 26 weeks the mother was given antenatal steroids. At 28 weeks she had an emergency caesarean section for unsuppressed labour. Three live born infants were delivered, two girls and one boy. Their birthweights were appropriate for gestational age. Triplet one was found to have fixed flexion contractures of her hips, knees and ankles (Fig. 1). Her hips were widely abducted and her ankles were in the equinovarus position. There was no spontaneous movement of her lower limbs and no response to noxious stimuli. Her lower limbs were wasted and arreflexic; however, there was no abnormality of her upper limbs. Her buttocks were wasted and a sacral ‘dimple’ was evident, the anus was patulous, and there was

constant dribbling of urine. A sensory level was approximated at T10. She was not dysmorphic, and her head circumference was on the 90th centile. The other two infants were normal. Her neonatal course was complicated by respiratory distress syndrome requiring exogenous surfactant, and she was intubated for two days. She had apnoea of prematurity and was on continuous positive airways pressure until day 35. A patent ductus arteriosus was closed with indomethacin and she was treated with phototherapy for hyperbilirubinaemia. Ultrasound examination of her head and kidneys was normal. Ultrasound examinations of her spine showed a 2 mm  3 mm  5 mm cystic lesion in the cord at thoracic vertebrae T10– 11 level. There was no bony abnormality of the vertebrae and sacrum, thus excluding spina bifida and sacral agenesis. A skeletal survey showed a scoliosis, there being eleven ribs on the right with fusion of ribs five and six. There were no other bony abnormalities. Magnetic resonance imaging of the spine revealed a thin dysplastic cord caudally from T5 –7. Cystic areas were confirmed at T10 –11 and lumbar vertebrae L2– L3. The spinal cord was tethered at L5– S1. Her placental pathology showed a pale underperfused placental plate with focal amnionitis. The placenta was trichorionic and triamniotic. Serology for toxoplasmosis, rubella and cytomegalovirus and herpes simplex was negative.

a

Westmead Hospital, Departments of Neonatal Medicine and Obstetrics, Wentworthville, Australia b The Children’s Hospital at Westmead, Department of Neonatology, New South Wales, Australia * Correspondence: Dr N. Badawi, Department of Neonatology, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales, NSW 2145, Australia. D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S 1 4 7 0 - 0 3 2 8 ( 0 2 ) 0 1 6 6 2 - 2

Fig. 1. Congenital paraplegia with flexion contractures. www.bjog-elsevier.com

CASE REPORT

Discussion A preterm infant with congenital paraplegia and a dysplastic spinal cord with normal vertebrae is described. The baby was one of triplets conceived following in vitro fertilisation. During the pregnancy multifetal pregnancy reduction was attempted. We hypothesise that the paraplegia in this infant was most likely a result of direct trauma during the selective reduction procedure and is an important complication which parents should be warned about. This is the first case of congenital paraplegia following a pregnancy where multifetal reduction was attempted. This distressing case has potential implications for in vitro fertilisation and multifetal reduction, especially as the development and widespread application of assisted reproduction technologies has resulted in dramatic increase in the number of multifetal pregnancies1,2. The incidence of assisted pregnancies in New South Wales, Australia is now 1% of all deliveries1. Congenital paraplegia apart from that due to spina bifida is a rare event2, as is paraplegia acquired in the neonatal period. The rarity of paraplegia in the newborn period is evidenced by the sporadic case reports in the literature, and the lack of studies examining causation and outcome. It is such an uncommon finding that it is not listed as a notifiable birth defect2. We identified only this one case of congenital paraplegia admitted to Westmead Hospital from January 1992 to January 2001. A comprehensive search of the hospital database was done using the terms congenital or infantile paralysis (excluding spina bifida). The incidence of congenital paraplegia is approximately 1:40,000, given that Westmead Hospital has 4500 deliveries per year 2. Possible aetiological factors for the paraplegia in this infant include direct trauma from the multifetal reduction procedure, intrauterine crowding, an antepartum hypoxic or ischaemic event, or an otherwise defined complication of in vitro fertilisation, with the result being segmental cord atrophy with paraplegia and contractures of both lower limbs. Multifetal reduction is usually done in the first trimester between eleven and twelve weeks of gestation as it is technically more difficult before then3,4. This infant was born with a dysplastic spinal cord, normal vertebrae and paraplegia with contractures of the lower limbs. We speculate that the paralysis may be caused by the attempted fetal reduction at ten weeks of gestation and the spinal cord atrophy may be a direct result of this. She has a spinal dimple in the lumbosacral area, which corresponds to the underlying pathology. The ‘dimple’ may be seen as the point of entry of the needle and subsequent injection. Although multifetal reduction increases the chance of a successful outcome of the pregnancy, a major risk associated with it is the loss of the ‘non-reduced’ fetuses4 usually four or more weeks after the procedure4,5. In selective reductions done in the first trimester the overall fetal losses D RCOG 2002 Br J Obstet Gynaecol 109, pp. 582 – 584

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up to 24 weeks is 7% – 16%4,6,7. There is no evidence in the literature that the procedure causes direct damage to the non-reduced fetuses3,4,6. Inadvertent damage to the surviving non-reduced fetus during selective termination can theoretically occur. Loss rates of the remaining fetuses increase with the greater starting and finishing numbers of the fetuses3,4,6 which may be related to the number of needle insertions and also to the quantity of non-viable fetal tissue remaining6. Perhaps of relevance to this case, is the fact that multifetal reduction is associated with a higher incidence of periventricular leukomalacia in infants whose mothers underwent the procedure8. Adjusted for in vitro fertilisation and twin pregnancy the odds ratio is 8.5 (95% CI 1.7– 42.2)8. Fetal death and retained non-viable tissue may cause an intrauterine inflammatory response and may initiate the production and release of vasoactive inflammatory cytokines such as interleukin-1, interleukin-6, tumour necrosis factor and interferon8,9 interleukin-6 is increased in amniotic fluid in women who have experienced fetal death after midtrimester amniocentesis10. These substances can lead to fluctuations in the fetal blood pressure with hypotension, resulting in reduced cerebral blood flow, initiating periventricular leukomalacia9. If this process is extrapolated the inflammatory process with episodes of hypotension may also cause hypoxic –ischaemic to the fetal spinal cord. In nearly all cases the multifetal reduction procedure is performed by a trans-abdominal approach done under ultrasound guidance, with injection of potassium chloride into the fetal heart4,5. While the literature suggests that this is generally a safe procedure3 – 5 it is possible the fetus with the anencephaly may have had direct trauma to the cranium, and the fetus with the paraplegia had direct trauma to the spinal cord. The question that remains unanswered is whether the procedure was performed by a qualified person and with ultrasound guidance. Direct trauma to the fetal spinal cord is described following penetrating injury to the mother’s abdomen11. To date there is no evidence of injury to the fetal spinal cord following amniocentesis or attempted fetal reduction; however, direct injury to the skin, chest, eyeball and limbs have been reported from the amniocentesis needle12,13. Birth defects are also known to occur more often in infants from multiple pregnancies but this is often confined to monozygous multiples14. In infants which are not monozygous, the birth defects tend to be positional in origin, and are probably related to reduced intrauterine space14. However, evidence is mounting that in vitro fertilisation and intracytoplasmic sperm injection are associated with increased risks of birth defects14. In the Western Australian study of birth defects with intracytoplasmic sperm injection, 7.4% of infants born from intracytoplasmic sperm injection are classified as having a major birth defect, which is twice as likely as the general population14. It may be hypothesised that in vitro fertilisation may have a role to play in this baby’s paraplegia, although paraplegia is

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CASE REPORT

not a birth defect that has been described with assisted conceptions2. Impairment of the vascular supply to the fetal spinal cord can result in infarction of the cord and subsequent limb paralysis. Hypoxic – ischaemic events that may be associated with this are periods of prolonged maternal hypotension15, severe in utero crowding in multiple pregnancy15,16, and a perinatal asphyxial event. Paraplegia in three twin and one triplet pregnancies has been reported16 and in all four infants the level of spinal cord injury was at the thoracolumbar region, as is in our infant. However, it is not clear whether all the infants that were affected belonged to the same pregnancy, and the possible aetiology was not elaborated. Ischaemic neonatal paraplegia has been reported to be associated with perinatal asphyxia17 – 19. Evidence of acute hypoxic –ischaemic spinal cord injury is seen most often in the lumbosacral segment, as was present here. While there was no evidence of acute intrapartum hypoxia there were antenatal risk factors, such as the history of infertility, the multiple pregnancy and abnormal fetal presentation. It is becoming increasingly evident that not all hypoxic ischemic encephalopathy occurs in the intrapartum period, and there are often antenatal causes, both maternal and fetal, that are contributory20,21. In conclusion, with the increasing utilisation of assisted conception, multifetal reduction may become more prevalent. The obstetric literature has tended to report on fetal loss rates and there has been little mention of potential complications such as periventricular leucomalacia or other complications such as the spinal cord abnormality in this baby.

References 1. Hurst T, Shafir E, Lancaster P. Assisted Conception Australia and New Zealand, 1997. Sydney: Australian Institute of Health and Welfare National Perinatal Statistics Unit: Assisted Conception Series No 4. AIHW Cat No. PER 10, 1999. 2. NSW Public Health Bulletin Supplement (No 2, Dec 1998). Mothers and Babies Report 1997.

3. Berkowitz RL, Lynch L, Chitkara U, Wilkins IA, Mehalek KE, Alvarez E. Selective reduction of multifetal pregnancies in the first trimester. N Engl J Med 1988;318:1043 – 1047. 4. Evans M, Dommergues M, Wapner RJ, et al. Efficacy of transabdominal multifetal reduction: collaborative experience among the world’s largest centres. Obstet Gynecol 1993;82:61 – 66. 5. Tabsh KMA. A report of 131 cases of multifetal pregnancy reduction. Obstet Gynecol 1993;82:57 – 60. 6. Evans M, Dommergues M, Timor-Tritsch I, et al. Transabdominal versus transvaginal multifetal pregnancy reduction: international collaborative experience of more than one thousand cases. Am J Obstet Gynecol 1994;170:902 – 909. 7. Ansen RPS. Unfinished feticide. J Med Ethics 1990;16:61 – 65. 8. Geva E, Lerner-Geva L, Stavorovsky Z, et al. Multiple pregnancy reduction: a possible risk factor for periventricular leukomalacia in premature newborns. Fertil Steril 1998;69:845 – 850. 9. Leviton A. Preterm birth and cerebral palsy: is tumor necrosis factor the missing link? Dev Med Child Neurol 1993;35:549 – 558. 10. Romero R, Munoz H, Gomez R, et al. Two thirds of spontaneous abortions/fetal deaths after genetic midtrimester amniocentesis are the result of a preexisting subclinical inflammatory process of the amniotic cavity. Am J Obstet Gynecol 1995;173:261. 11. Amine A. Spinal cord injury in a fetus. Surg Neurol 1976;6:369 – 370. 12. Holmes L. Severe malformation in one foot from amniocetesis needle injury. Clin Dysmorphol 1997;6:273 – 280. 13. Epley SL, Hanson JW, Cruikshank DP. Fetal injury with midtrimester amniocentesis. Obstet Gynecol 1979;53:77 – 80. 14. Kurinnczuk JJ, Bower C. Birth defects in infants conceived by intracytoplasmic sperm injection: an alternative hypothesis. BMJ 1997; 315:1260 – 1265. 15. Suri S, Salfield S, Baxter P. Congenital paraplegia following maternal hypotension. Dev Med Child Neurol 1999;41:273 – 274. 16. Ruggieri M, Smarason A, Pike M. Spinal cord insults in the prenatal, perinatal, and neonatal periods. Dev Med Child Neurol 1999;41: 311 – 317. 17. Singer R, Joseph K, Gilai A, Meyer S. Non traumatic, acute neonatal paraplegia. J Pediatr Orthoped 1991;11:588 – 593. 18. Clancy RR, Sladky JT, Rorke LB. Hypoxic ischaemic spinal cord injury following perinatal asphyxia. Ann Neurol 1989;25:185 – 189. 19. Sladky JT, Rorke LB. Perinatal hypoxic/ischaemic spinal cord injury. Pediatr Pathol Lab M 1986;6:87 – 101. 20. Badawi N, Kurinczuk JJ, Keogh JM, et al. Antepartum risk factors for newborn encephalopathy: the Western Australian case control study. BMJ 1998;317:1549 – 1553. 21. MacLennan A, for the international Cerebral Palsy Task Force. A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement. BMJ 1999;319:1054 – 1059. Accepted 1 August 2001

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