Adverse effect of amniofetography on fetal thyroid function

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Adverse effect of amniofetography on fetal thyroid function F.

RODESCH,

M,

CAMLiS,

A,

M,

DODION,

F.

DI~LANGE,

PH.D.

PH.D.

ERMANS,

J.

Btxds.

M.D.,

M.D.,

PH.D

M.D. M.D.,

PH.D.

Ee@utn

.-l rnniof>tography ;.Y a valuabh~ tooL ,for tlw diagnosis of.fptal m&jormation~s. Thi.s twhrGp is bping WY~ routiwly in pwgnanci~s car?ing a high risk of~xt~~~ljAa1 ma1formation.s. Thw aw venb~ &I~~ $wblishtd data concwning thp of radiopapw dws, containing larg(j amounts of iodide, on fptal thyroid fun&on. Wp haw pqforrrwl trial d&>rmination,s of’wrum thvrotropin and thyroxine in ,stwn nwborn infants to a~w.~ the ~ff~~~t of amniof~tograph~ on ,fetal thy&d function. This work &monstrat(ss that ~~,n~~i(~f~t~~~~ap)~y. induces a transi&t impairmint of @al thyroid,function. (AM. J. OBSTET. GYNECOL. 126: 723, 1976.)

effort

AMNIOGRAPHY

niotic

OUTLINES

cavity and allows

radiographicaly the amvisualization of the fetal gas-

trointestinal tract. Fetography makes use of the affinity of a fat-soluble contrast medium for vernix caseosa, providing a clear-cut outline of fetal soft tissue. Amniofetography (AFG), in which a combined injection of a water- and a fat-soluble radiopaque dye is used, is clearly a valuable tool for the diagnosis of fetal malformations. Today AFG is commonly performed in pregnancies carrying a high risk of external fetal malformations. It is well established that protracted treatment with iodides can lead to thyroid enlargement and goiter in adults and chilclren. Cases of congenital goiter subsequent to chronic intake of large amounts of iodin? bl

From the Dejmrtment of’ Obstetrics and Gynecology, Human Rtprodu&n Research Unit, lnterdisciplina?y Institute for Research in Human and Nu&ar Biology, and the Departmnts of RadinCotopes and Pediatrics, H6pital Saint-Pierre, Fw Uniter.+ OJBrusels. Supported by “For& de la Recherche Scient$ique Mkdicale” (Belgium) and by a contract from the Mini&e de la Politique Sctinta$iqw (Belgium) within the framework of the Association Euratom-University of ~~L.~.s~~~-U?liv~r.~i~~ of F%a. Reprint

request,s:

Dr. F. Rodesch,

Gynecology and Ob,~t&cs, Haute,

322-l

000

Brusels,

Department

H+ital

of

Saint-Pierre, Rue

Belgium.

723

724

Ftodesch

Table blood

et

al.

I. Serum Td and TSH concentrations and at the fifth day of life

I


2 3 4 5 6 7


9.9 3.5 31.5* >50* 51.0*

q.2 11.1 8.4 16.5 7.2

7.0 27.0* 51.0* 3&5* 49.0* 50.0* 51.0*

in cord

7.5 11.4 5.1*

*Abnormal results according to the studies of Delange and associate? for TSH and of Fisher and Sack’ for T+ the mother have also been well d0cumented.i However, there are very few published data* relative to the effects on the fetal thyroid of radiopaque contrast dyes injected into the amniotic cavity. Both the water- and lipid-soluble dyes used in AFG contain large amounts of iodide. The aim of this study was to assess the effect of AFG on the fetal thyroid. Thyroid function of the newborn infant was evaluated by serial determinations of serum thyroxine (Td) and thyrotropin (TSH). 0ur data demonstrate an adverse effect of AFG on neonatal thyroid function. This risk of transient hypothyroidism should be considered as a strong deterrent against unnecessary AFG.

Methods AFG. The site selected for amniocentesis was the space occupied by the fetal arms and legs. Amniocentesis was performed with the use of local anesthesia. The needle tip entered the amniotic cavity with the stylet in place, and placement was verified by the ease of removal of amniotic fluid. A catheter was then introduced through the needle, and the needle was removed. The contrast materials were injected through the catheter. For the purpose of fetal delineation, 12 ml. of iodized ethyl esters of the fatty acids of poppy seed oil* was used. In all cases, 30 ml. of a water-soluble contrast medium (meglumine diatrizoatet) was injected simultaneously. Two roentgenograms were obtained 24 hours after the injection. Data on seven AFG’s are reported. The indication for the procedure was a high risk of fetal malformation: polyhydramnios (four cases) and severe in*Lipiodol TAngiografin.

trauterine growth retardation (three cases). No fetal malformations were observed on roentgenograms; this was confirmed by clinical examination of the newborn infants. None of the seven pregnant women had any symptoms of thyroid disease or any evidence of thyroid enlargement on clinical examination. Moreover, the serum Td and TSH levels conhrmed the euthyroid state. Assessment of thyroid function in the newborn infant. Systematic screening for congenital hypothyroidism has been performed by our maternity service since July, 1974. The method used has been described in detail elsewhere.3 Serum TSH has been measured on the fifth day with the use of the TSH Phadepas kit.* The mean level (2 standard error) for 901 patients is 1.7 ?Z I .O PU per milliliter; 12 PIJ per milliliter was considered the upper limit of normal as the results were below this value in 99.2 per cent of the cases. Newborn infants with a serum TSH level above the “critical” value underwent control investigations. Serum Td was determined according to the method of Murphy and Pattee.’ In the present investigation, the serum TSH concentration was measured systematically on the fifth day with simultaneous T4 determinations in four cases. In five cases, serum Td and TSH were determined in cord blood.

Results Table I shows the results of serum T4 and TSH measurements in the seven neonates at birth and at the fifth day of life. The cases are classified according to the increase in time interval between AFG and delivery. The most striking observation is that six of seven infants exhibited a very high TSH level at the fifth day of life, ranging from 27.0 to 51.0 PU per milliliter, i.e., markedly above the upper Iimit of 12 PU per milliliter. Cord Td and TSH concentrations were normal in two cases, but cord TSH was increased in three other subjects (Nos. 5.6, and 7). It should be pointed out that this situation was observed only when the delay between AFG and birth was at least five days. Moreover, an abnormally low serum T4 concentration at the fifth day was observed only in the patient with the longest delay, i.e., 13 days. Table II summarizes the results of the follow-up examinations. In three cases (Nos. 4, 5, and 7), TSH had reverted to normal, and the results of other follow-up examinations were also normal. However, in two cases (Nos. 3 and 6), TSH was still markedly increased and Td was decreased. In Case No. 6, a

F. *Pharmacia

AB,

Uppsala,

Sweden.

Vdume

126

Amniofetography

Number fi

Table

II. Kesults

case No.

of the follow-up

examinations

TSH (dJhL$fth

a$)

Day

TSH (jLlJlVL1.)

8 9

14.7*

3

51.0*

19

51.0*

4

36.5*

17 38 16 17

5.8

5

49.0*

6 7

50.0* 51.0*

*Abnormal

on fetal

thyroid

725

in the seven cases

7.0 27.0*

I

2

effect

1.9 >250* 3.9

T4 (pgllO0

ml.)

9.7 14.6 4.3* 7.0 13.5 3.1* 6.6

Clinical fi?ldings

None Apathy and jaundice None None NOIlC Goiter None

results according to the studies of Delange and associates’ for TSH and of Fisher and Sack’ for Ta

palpable goiter was confirmed by scintigraphy. In Case No. 2, serum TSH was moderately increased (14.7 /LU per milliliter) and T4 was normal. Nevertheless, the infant exhibited an episode of jaundice and apathy compatible with hypothyroidism. These three patients (Nos. 3, 6, and 2) received thyroid extracts for two to four weeks.

Comment The present work shows that AFG impairs thyroid function of the newborn infant and may result in congenital hypothyroidism. Of the seven newborn infants in our series, six exhibited strikingly increased serum TSH levels at the fifth day of life. Follow-up examinations performed in the next few days clearly confirmed the diagnosis of hypothyroidism in two cases (Nos. 3 and 6) by the association of an increased TSH level and a decreased Td level. Thyroid failure could be strongly suspected in a third case (No. 2), despite a normal Tq value, on the basis of increased TSH and clinical symptoms (apathy and unexplained jaundice) which disappeared immediately after thyroid hormone treatment. In the three other cases (Nos. 4, 5, and 7), TSH and T., concentrations had reverted to normal at the time of follow-up. Furthermore, impairment of thyroid function was suspected even at birth in three cases on the basis of increased TSH levels in the cord blood. The precocity of the appearance of the biochemical abnormalities seemed to be correlated with the time delay between AFG and delivery. The results of the follow-up examinations of the patients have shown a rapid clinical and biochemical normalization either spontaneously or after a short period of treatment with thyroid extracts. This indicates that impairment of thyroid function in the newborn infant after AFG is transient. Nevertheless, due to the vulnerability of the human brain in the perinatal period, even silent and transient hypothyroidism must

be diagnosed and treated promptly it) order to avoid any cerebral damage.’ The mechanism responsible for thyroid impairment is most probably, as in congenital iodide goiter, via a toxic effect of iodide on intrathyroidal hormonogenesis (Wolff-Chaikoff effect’) which accounts for the delay between AFG and TSH elevation and for the transient character of the thyroid dysfunction. This interpretation is supported by the fact that the urinary concentration of iodide in one newborn inl’ant was 900 pg per 100 ml. at birth and in another was 230 /~g per 100 ml. at one month, about 80 to 2.000 times higher than normal in Belgium. Our conclusions are in disagreement Lsith those of Morrison and associates.’ These author% concluded that AFG has no adverse effects on thyroid function on the basis of normal serum Ta levels and triiodothyronine resin uptake in the first day of life. They did not measure serum TSH levels, which are definitely better for detecting slight thyroid impairment.’ It is also very important to point out that Morrison and associates used only a water-soluble contrast medium (meglumine diatrizoate*). These authors explained the absence of perturbation of thvroid function by the fact that, as shown by their chromatographic studies of amniotic fluid aliquots, the iodine remained organically bound until it was eliminat.ed from the amniotic compartment within two clr four days after injection. It is unnecessary to emphasize the potential uses of outlining the fetus radiographically, as AFG is now being used universally. The contribution of this paper is to underline the necessity of systematically and carefully evaluating the thyroid function of’ these newborn infants in order to be able to correct immediately any thyroid disturbance. *Renografin-60.

REFERENCES 1. Vagenakis, A. G., and Braverman, L. E.: Adverse effects of iodides on thyroid function, Med. Clin. North Am. 59: 1075, 1975. 2. Morrison, J. C., Boyd, M., Friedman, B. I., Bucovaz, E. T.. Whybrew, W. D., Koury, D. N., Wiser, W. L., and Stewart, A. F.: The effects of Renografin-60 on the fetal thyroid, Obstet. Gynecol. 42: 99, 1973. 3. Delange, F., Camus, M., Winkler, M., Dodion, J., and Ermans, A. M.: Serum thyrotropin determination at the fifth day of life as a screening procedure for congenital hypothyroidism, Arch, Dis. Child. In press.

4.

Murphy, B. E. P., and Pattee, C. J.: Determinatiotl 01 thyroxine utilizing the property of protein-binding,,J. (Xn. Endocrinol. Metab. 24: 187, 1964. 5. Barnes, N. D.: Serum TSH measurement in children witI1 thyroid disorders. Arch. Dis. Child. 50: 497, i97.5. 6. Fisher, D. A., and Sack, J,: Thyroid function in the neonate and possible approaches to newborn screening fog. hypothyroidism, In FishTr, D. A., and Burrow. G. X., editors: Perinatal Thyroid Physiology and Disease, Kroc Foundation Series No. 3, New York, 1975, Raven Press, p. 197.