Craen, Margarita

De Praeter, Claudine

Smets, Koenraad

Vanhaesebrouck, Piet

Verstraete, Alain

Zecic, Aleksandra

English

Ghent University Academic Bibliography

ORIGINAL PAPERPiet Vanhaesebrouck Æ Alain G. VerstraeteClaudine De Praeter Æ Koenraad SmetsAlexandra Zecic Æ Margarita CraenTransplacental passage of a nonionic contrast agentReceived: 4 January 2005 / Accepted: 16 February 2005 / Published online: 30 March 2005 Springer-Verlag 2005Abstract We report the presence of iopromide in thebowel and urine of a preterm infant, born 10 days afterintravenous administration of the nonionic monomer tohis mother. Excessive urinary iodine excretion andborderline hyperthyrotropinaemia were observed in theinfant. Moreover, crossing of the fetal blood-brainbarrier was demonstrated by detection of the angio-graphic material in CSF and thus direct fetal neurotoxiceﬀects cannot be excluded. Conclusion: These widelyused contrast media may cross the placenta and accu-mulate in various fetal tissues in signiﬁcant amountscausing possible neonatal toxicity. Therefore the peri-natal safety of these diagnostic agents should at least bequestioned.Keywords Iopromide Æ Nonionic monomer Æ Thyroid ÆTransplacental passage Æ Urinary iodineIntroductionAlthough the newer nonionic contrast media used forconventional X-ray and MRI studies are well-toleratedin humans, very little is known about placental transferand the possible eﬀects on the fetus [7]. In two animalmodels no placental passage of nonionic compoundscould be detected [2,16]; however, animal studies are notalways predictive of human response and adequate, well-controlled studies in humans have not been done. In onerecently published report, placental transfer of iohexol(Omnipaque) within 24 h was demonstrated postnatallyby fetal gut opaciﬁcation in a human twin pregnancy[13]. We report the presence of iopromide not only in thebowel but also in urine and CSF together with transientmild thyroid dysfunction in a preterm infant afterintravenous administration of the contrast medium tothe mother 10 days before birth.Case reportAn obese (body weight 107 kg) 26-year-old primiparawas transferred to the maternity ward at 27 weeks ofgestation because of threatening preterm labour. Toc-olysis was initiated. Two days later, because of acutedyspnoea and low oxygen saturation, the attendantradiologist deemed the performance of pulmonary CTangiography necessary to exclude pulmonary embolism.A high dose of the nonionic, iodinated contrast mediumiopromide (200 ml Ultravist-370, Schering) was givenintravenously. No lung embolism could be detected. Tendays after the CT angiogram, membranes rupturedspontaneously and 1 h later a preterm boy was bornvaginally at 29 weeks’ gestation. Apgar scores were 7and 9 at 1 and 5 min, respectively. Birth weight was1491 g. The baby had only mild respiratory distress. Nogoitre was observed. A plain abdominal X-ray ﬁlmperformed on day 1 showed intraluminal gastrointesti-nal opaciﬁcations consistent with the presence ofradiographic contrast material. This unexpected ﬁndingwas conﬁrmed by a lateral view ﬁlm (Fig. 1). Convul-sions or abnormal neurological behaviour were notobserved. The iopromide level was 0.13 ng/ml in a urinesample on day 8. Iopromide concentration in CSF onday 9 was 0.1 ng/ml. The contrast monomer was nolonger detectable in a urine sample on day 12. Iopromidewas determined in CSF and urine by a method modiﬁedP. Vanhaesebrouck (&) Æ C. De Praeter Æ K. Smets Æ A. ZecicDepartment of Neonatology,Ghent University Hospital, De Pintelaan 185,9000 Ghent, BelgiumE-mail: piet.vanhaesebrouck@UGent.beTel.: +32-9-2403527Fax: +32-9-2406105A. G. VerstraeteDepartment of Clinical Biochemistry,Ghent University Hospital, Ghent, BelgiumM. CraenDepartment of Paediatric Endocrinology,Ghent University Hospital,Ghent, BelgiumEur J Pediatr (2005) 164: 408–410DOI 10.1007/s00431-005-1659-2from those of Hirsch et al. [10] and Putschew et al. [14].Liver and renal function tests, ionogram, as well asclotting screening tests were all normal. Urinary iodineconcentration on day 8 of life was 880 lg/l (normalreference value <200 lg/l). Iodine containing solutionswere not used in the delivery room or during neonatalcare. Serum FT4 levels were 1.1 and 1.2 ng/dl on days 7and 31 of life, respectively (reference range 0.9–1.7 ng/dl). The corresponding levels of TSH were 2.7 and6.2 mU/l (95% age-speciﬁc conﬁdence intervals 0.45–4.12 mU/l). Apart from a persistent apnoea syndrome,the further hospital course was uneventful. On follow-upat the corrected age of 4 months, the child showednormal neurodevelopment, although some axial hyper-extensive posturing was suspected. At that time, cerebralultrasound and thyroid function were normal (serumFT4 1.3 ng/dl and TSH 2.3 mU/l).DiscussionTransplacental passage and fetal uptake of an ionicagent such as diatrizoate has been demonstrated in earlyhuman pregnancy [5]. Neonatal intestinal opaciﬁcationsecondary to transplacental passage of an ionic contrastmedium (Renograﬁn-60) after maternal excretory urog-raphy was ﬁrst documented by Kelleher et al. in 1979[11].In rodent and non-rodent animal models, nonionicmonomers such as iobitridol, iohexol and iopromideadministered in comparable doses as used clinically inconventional X-ray imaging studies were shown to berapidly excreted with no clear passage across the pla-centa and no retention in amniotic ﬂuid nor fetal tissues[2,16]. However, one recent report documented placentaltransfer of a nonionic contrast medium by the radio-graphic appearance of contrast material in the intestinesof preterm twin fetuses after intravenous administrationof iohexol to the pregnant mother for angiography 17 hbefore birth [13]. The present report conﬁrms thetransplacental passage of another nonionic monomeradministered to a pregnant mother 10 days before birth.The contrast agent can pass across the placenta into thefetal circulation, be excreted by the fetal kidneys into theamniotic ﬂuid and can be swallowed by the fetus.Alternatively, contrast medium from the maternal cir-culation may equilibrate directly into the amniotic ﬂuidby passive intramembranous diﬀusion and this ﬂuid isthen also swallowed by the fetus [9].Iopromide is reported not to pass the blood-brainbarrier (Schering documentation); however, in our pa-tient, iopromide could still be detected in CSF 20 daysafter contrast administration to the mother. It is knownthat intravascular contrast agents can occasionally causeselective osmotic disruption of the blood-brain barrierand may induce signs of direct neurotoxicity such astransitory cortical blindness, convulsions, apnoea andsedation [15]. Iopromide is not indicated for intrathecaluse. When the agent is given intrathecally, serious ad-verse reactions have occurred, including death, convul-sions, cerebral haemorrhage and coma [3].Previous studies have shown that preterm infants arevery sensitive to an iodine load with a signiﬁcant risk ofhypothyroidism [12]. Ares et al. [1] reported that thyroidcomplications due to iodine exposure should be sus-pected in those premature infants with urinary iodineconcentrations greater than 200 lg/l. The iodine over-load and mild, albeit transient, neonatal hyperthyro-tropinaemia put our patient at risk of subclinicalhypothyroidism at a critical age for the normal devel-opment of the nervous system in later infancy [4].However, it is reassuring that (transient) hypothyroid-ism or hyperthyrotropinaemia were not detected in thepatients of Dembinski et al. [6] receiving iopromidepostnatally for diagnostic imaging of non-radio-opaquecentral silastic catheters. Degradation of iopromideproduces about 0.06 mg of free readily absorbable io-dide per 100 ml contrast medium, which is signiﬁcantlyless than ionic and also most other nonionic agents. Themother is also at risk for hypothyroidism due to theWolﬀ-Chaikoﬀ eﬀect (blockade of iodide absorption bythe thyroid gland) induced by the acute iodine overload.Iodine-containing contrast media can induce transientsubclinical hypothyroidism in adult euthyroid patientsFig. 1 Anteroposterior (A) andlateral view (B) X-ray ﬁlms ofthe abdomen on day 1 of lifeshowing the presence ofcontrast material (arrows)409[8]. Therefore our patient and his mother will be rou-tinely monitored.The potential hazards of fetal exposure to radio-graphic non-ionic contrast agents should be furtherinvestigated and for the time being their perinatal safetyshould still be questioned. In the absence of speciﬁcstudies, it is recommended that when no safer alternativeexists, these products should be used very cautiously inpregnant women.References1. Ares S, Pastor I, Quero J, Morreale de Escobar G (1995)Thyroid complications, including overt hypothyroidism, re-lated to the use of non-radiopaque silastic catheters for par-enteral feeding in prematures requiring injection of smallamounts of an iodinated contrast medium. Acta Paediatr 84:579–5812. Bourrinet P, Dencausse A, Havard P, Violas X, Bonnemain B(1995) Transplacental passage and milk excretion of iobitridol.Invest Radiol 30: 156–1583. Caille´ JM, Allard M (1988) Neurotoxicity of hydrosoluble io-dine contrast media. Invest Radiol 23: S210–S2124. Calaciura F, Motta RM, Miscio G, Fichera G, Leonardi D,Carta A, Trischitta V, Tassi V, Sava L, Vigneri R (2002)Subclinical hypothyroidism in early childhood: a frequentoutcome of transient neonatal hyperthyrotropinemia. J ClinEndocrinol Metab 87: 3209–32145. Dean PB (1977) Fetal uptake of an intravascular radiologiccontrast medium. Fortschr Geb Rontgenstrahlen NuklearmedErganzungsbd 127: 267–2706. Dembinski J, Arpe V, Kroll M, Hieronimi G, Bartmann P(2000) Thyroid function in very low birth weight infants afterintravenous administration of the iodinated contrast mediumiopromide. Arch Dis Child Fetal Neonatal Ed 82: F215–F2177. Faykus MH, Cope C, Athanasoulis C, Druy EM, Hedgcock M,Miller FJ, Bron K (1994) Double-blind study of the safety,tolerance, and diagnostic eﬃcacy of iopromide as comparedwith iopamidol and iohexol in patients requiring aortographyand visceral angiography. Invest Radiol 29: 98–1018. Gartner W, Weissel M (2004) Do iodine-containing contrastmedia induce clinically relevant changes in thyroid functionparameters of euthyroid patients within the ﬁrst week? Thyroid14: 521–5249. Gilbert WM, Eby-Wilkens E, Tarantal AF (1997) The missinglink in rhesus monkey amniotic ﬂuid volume regulation: in-tramembranous absorption. Obstet Gynecol 89: 462–46510. Hirsch R, Ternes TA, Lindart A, Haberer K, Wilken RD(2000) A sensitive method for the determination of iodinecontaining diagnostic agents in aqueous matrices using LC-electrospray-tandem-MS detection. Fres J Anal Chem 366:835–84111. Kelleher J, Feczko PJ, Radkowski MA, Griscom NT (1979)Neonatal intestinal opaciﬁcation secondary to transplacentalpassage of urographic contrast medium. Am J Roentgenol 132:63–6512. L’Allemand D, Gruters A, Beyer P, Weber B (1987) Iodine incontrast agents and skin disinfectants is the major cause forhypothyroidism in premature infants during intensive care.Horm Res 28: 42–4913. Moon AJ, Katzberg RW, Sherman MP (2000) Transplacentalpassage of iohexol. J Pediatr 136: 548–54914. Putschew A, Schittko S, Jekel M (2001) Quantiﬁcation of tri-iodinated benzene derivatives and X-ray contrast media inwater samples by liquid chromatography-electrospray tandemmass spectrometry. J Chromatog A 930: 127–13415. Schulte-Altedorneburg G, Ru¨b K, Scheglmann K (2004)Simultaneous ischemic and neurotoxic brain damage aftercoronary angiography. Neurol Res 26: 79–8216. Tauber U, Mutzel W, Schulze P (1989) Whole body autora-diographic distribution studies on nonionic X-ray contrastagents in pregnant rats. Fortschr Geb Ro¨ntgenstrahlenNuklearmed Erga¨nzungsbd 128: 215–219410

Transplacental passage of a nonionic contrast agent

https://biblio.ugent.be/publication/319129/file/6788757.pdf

Transplacental passage of a nonionic contrast agent

Abstract

Similar works

Full text

Available Versions

Ghent University Academic Bibliography