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Fulltext Lipiodol
Fulltext Lipiodol
Judith A. W. Webb
Henrik S. Thomsen
The use of iodinated and gadolinium contrast
Sameh K. Morcos
Members of Contrast Media Safety
media during pregnancy and lactation
Committee of European Society of
Urogenital Radiology (ESUR)
gut [28]. Bourrinet et al. [24] estimated that only 0.003% of markedly elevated TSH levels of 27–51 μU/ml (normal 12
the injected dose of iohexol and iobitrol reached fetal blood μU/ml) in six of seven neonates at 5 days. In only three of
in the rabbit. these was the cord TSH increased at birth. Subsequently,
In man, a neonatal pyelogram following administration two of the babies developed hypothyroidism which was
of an intravenous ionic agent prenatally to the mother was satisfactorily treated with thyroxine, and thyroid failure was
first described in 1963 [29]. Intravenous sodium diatrizoate suspected in a third baby whose clinical symptoms re-
(120 ml of Renografin, concentration not stated) was given sponded to thyroxine [2]. Amniography using water- and
to two pregnant women with impaired renal function (cre- lipid-soluble contrast medium 4 days before delivery was
atinine levels 132 and 176 μmol/l). Abdominal radiographs associated with hypothyroidism in another infant [40]. The
of their babies at 4 and 1–2 days after contrast medium Lipiodol used for amniography is deposited on the vermix
injection showed opacification of the small and large bowel and then can be absorbed by the fetus over a prolonged
[30]. In impaired renal function the plasma contrast medium period of time. Lipiodol given intramuscularly persists in
concentration in the mothers would remain high longer than the body for a long period and is used as a treatment for
in individuals with normal renal function with the pos- iodine deficiency including iodine deficiency in pregnancy.
sibility for more contrast medium to cross the placenta. In It results in urinary iodine levels above baseline for more
one woman who had intravenous urography with the ionic than 12 months [41]. In rabbits, Lipiodol crossed the pla-
agent sodium iothalamate (dose not stated) 24 h before centa and accumulated in the fetal thyroid [42].
amniocentesis, the total iodine concentration in amniotic Amniography using only the water-soluble agent me-
fluid was 380 μg/ml, much higher than in normal subjects glumine diatrizoate injected into the amniotic fluid was
(4.4 ± 1.6 ng/ml). In another woman, in whom amniocen- associated with no significant change in cord blood T4 and
tesis was not done until 22 days after urography, the am- T3 levels in 28 subjects compared to 25 controls [28]. How-
niotic fluid iodine level was 29 ng/ml, suggesting that ever, later samples were not obtained. In pregnant women
contrast media diffuse out into the mother through the who have had intravenous urography, high amniotic fluid
placenta, as well as diffusing into the fetus [31]. Following iodine levels were detected 24 h after intravenous contrast
the nonionic agent iohexol given to a pregnant woman for medium, but had declined by 22 days [31]. This led to the
angiography, there was opacification of the intestine of her hypothesis that contrast media may traverse the placenta in
twin neonates [32]. Contrast media injected into the am- both directions and therefore may be excreted by the moth-
niotic fluid directly the day before intrauterine transfusion er. Water-soluble contrast agents such as meglumine diatri-
also subsequently opacified the fetal gut [33]. zoate only contain relatively small amounts of free iodide,
and it is this substance which is potentially harmful to the
fetal thyroid. The permitted upper level of free iodide in
Potential harmful effects contrast medium of concentration 300 mg I/ml is below 50
μg/ml immediately after production and below 90 μg/ml
Thyroid after 3–5 years. Usually the free iodide concentration is less
than one tenth of these amounts [43]. If 150 ml of contrast
Depression of fetal thyroid function is the most important medium (300 mg I/ml) is used, for example for CT pul-
potential harmful effect of iodinated contrast media within monary angiography in a pregnant woman, and the free
the fetus. By 12 weeks the fetal thyroid is synthesizing iodide content is 50 μg/ml, the total dose of free iodide is
thyroxine (T4) under the influence of thyroid stimulating 7,500 μg. There is no experimental data to indicate how
hormone (TSH). From 30 weeks onwards, serum triiodo- much of this free iodide crosses the placenta, how long it
thyronine (T3) levels increase to the time of birth. The fetal remains in the fetus, or what its effect on the fetal thyroid
pituitary–thyroid axis is considered to be independent of the might be. The likelihood is that free iodide in the fetus
mother [34]. At delivery, TSH rises rapidly to peak at 30 diffuses out across the placenta rapidly and the fetal thyroid
min and then declines over the next 48 h. At the same time is only exposed for a short period of time. In women with
T3 and T4 levels increase and usually return to normal by 2 impaired renal function, exposure of the fetus is likely to be
weeks [35–37]. Fetal thyroid function is important for for longer because blood levels of contrast medium or free
normal development of the central nervous system [38, iodide remain higher for longer.
39]. Medicines containing iodine are generally considered In the neonate, high doses of nonionic contrast agents
to be contraindicated in pregnant women because of the given intravenously do not appear to upset thyroid function.
possibility of iodide uptake by the fetal thyroid leading to Thus in ten neonates aged 10–28 days who had received
fetal hypothyroidism [23]. 1,500 mg I/kg of iopamidol, no abnormality in thyroid
Amniography using both Lipiodol (iodized ethyl esters function could be detected at 10 and 30 days after the study
of the fatty acids of poppy seed oil) and meglumine diatri- [44].
zoate injected into the amniotic fluid was associated with
1237
metrizamide (5.06 mg) given intrathecally, only 0.02% of mine (0.005 or 0.01 mmol/kg) used as an oral contrast agent
the dose was excreted in the milk by 44 h [57]. Even after with mannitol in adults was not associated with a change in
fat-soluble cholecystographic agents, iodine excretion in signal intensity of the urine after contrast medium, indicat-
the milk was very low [58]. Furthermore, only very small ing significant gadolinium absorption was unlikely [63].
amounts of the iodinated contrast agents which enter the The recommended pediatric dose of gadolinium agents is
gut in milk are absorbed into blood. Thus when the non- 0.1–0.2 mmol/kg, and this is well tolerated in infants less
ionic agent metrizamide was used as an oral contrast agent, than 6 months [64, 65]. The amount of gadolinium agent in
only 0.4% was excreted in the urine in the 1st day, and a the gut of a breast-fed infant after gadolinium has been
total of 0.8% by the end of the 3rd day [59]. The recom- given intravenously to the mother is less than 1% of the
mended dose of iohexol for pediatric urography is 900 mg recommended intravenous dose for the infant [3]. In all
I/kg for babies under 6.5 kg, and 600 mg I/kg for babies gadolinium agents the gadolinium is chelated to minimize
7.0 kg or more [60]. The oral dose of iohexol received in toxicity. Nonetheless, small amounts of free gadolinium
24 h by the baby in the milk after a maternal dose of 350 may remain in animals following the use of these agents.
mg I/kg has been estimated to be 1.7 mg I/kg, which is Again, the taste of the milk may be altered if it contains
0.002% of the maximum dose recommended to be given gadolinium contrast medium.
intravenously for urography [56, 59]. The likelihood of
either direct toxicity or allergic reaction is therefore ex-
tremely low. As with other drugs and foodstuffs, the taste Conclusion
of milk may be altered if contains contrast medium.
The amounts of both iodinated and gadolinium agents likely
to reach the neonatal circulation from the milk when a
Gadolinium MR agents lactating mother is given either type of agent intravascularly
are very small. They are significantly less than the amounts
Very low levels of gadolinium contrast medium are detected which may be administered to neonates during imaging
in the milk after intravenous administration. In 20 lactating procedures. The extremely low risk to the neonate from the
women given gadopentetate dimeglumine (0.1 mmol/kg in contrast medium may therefore not be considered sufficient
19, and 0.2 mmol/kg in 1) the cumulative gadolinium ex- to warrant the potential disruption to both the mother and
cretion in milk over 24 h was less than 0.04% of the intra- the baby by ceasing breast-feeding for 24–48 h after con-
venous dose (0.57 ± 0.71 μmol) [3]. In a lactating woman trast medium. Based on this review, guidelines (Table 1)
who received gadopentetate dimeglumine (0.1 mmol/kg) have been proposed and approved at the 11th European
the cumulative excretion of gadolinium was 0.011% of the Symposium on Urogenital Radiology.
total dose given [61]. In another lactating woman who re-
ceived the same dose of gadopentetate dimeglumine the Acknowledgements We thank Dr M.O. Savage, professor of Pe-
cumulative gadolinium excretion was 0.023% of the admin- diatric Endocrinology, St. Bartholomew’s Hospital, London EC1A
istered dose over 24 h [62]. 7BE, for his helpful comments.
When gadolinium contrast agents enter the gut, only very
small amounts are absorbed. Thus, gadopentetate dimeglu-
1239
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