6
Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis Fernando Moya, MD, Patricia Mena, MD, Arnaldo Foradori, MD, Mario Becerra, MD, AIvaro Inzunza, MD, and Alfredo Germain, MD From the Division of NeonataI-Perinatal Medicine, Departments of Pediatrics and Obstetrics and Gynecology, Universityof Texas Southwestern Medical Center at Dallas, the Hospital Sot- ero del Rio, Puente Alto, Chile, and the Departments of Nuclear Medicine and of Obstetrics and Gynecology, Universidad Catolica de Chile, Santiago, Chile We evaluated the response of preterm fetuses to maternal intravenous injection of 400 ~g of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group com- pared with the control group (12.0 _+ 1.6 vs 5.6 • 0.5 mU/L; p <0.005); however, maternal triiodothyronine (1'3) values remained unchanged. Significant eleva- tions of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 • 7.7 vs 8.4 • 0.9 mU/L [p <0.002] and 1.3 _+ 0.07 vs 0.7 _+ 0.04 nmol/L or 87 + 5 vs 49 3 ng/dl (p <0.001], respective- ly). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 • 5 vs 86 • 10 nmol/L or 10.5 • 0.4 vs 6.7 _+ 0.8 #g/dl [p <0.001] and 212 • 31 vs 105 • 28 ~g/L (p <0.05], respectively). Two hours after birth, a signif- icant increase in T3but not T4levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal admin- istration of this hormone results in marked stimulation of the preterm fetal pitu- itary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of Tz, (J PEDIATR 1991;119:966-71) Thyrotropin releasing hormone crosses the placenta readily in laboratory animals and human beings.~4 Once in the fe- tal circulation, TRH stimulates the release of thyrotropin and prolactin by the fetal pituitary gland. We have reported Presented in part at the Southern Society for Pediatric Research Meeting, New Orleans, La., Jan. 17-19, 1990 (published in abstract form: Clin Res 1990;38:48A and Pediatr Res 1990; 27:81A). Submitted for publication May 6, 1991; accepted June 21, 1991. Reprint requests: Fernando R. Moya, MD, Associate Professor of Pediatrics, Obstetrics, and Gynecology,Department of Pediatrics and Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-9063. 9/23/31953 that maternal administration of 400 ~g of TRH 2 hours be- fore cesarean section at term results in elevations of cord blood levels of thyrotropin and triiodothyronine. 4 A higher dose of TRH (600/zg) achieved similar results. In that study the postnatal surge of thyrotropin and T3 in term infants RDS Respiratory distress syndrome T3 Triiodothyronine T4 Thyroxine TRH Thyrotropin releasing hormone exposed to TRH before delivery was similar to that observed in control infants. Recently, other effects of TRH in the fetus have received considerable attention. Fetal exposure to TRH seems to ac- 966

Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

Embed Size (px)

Citation preview

Page 1: Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

Fernando Moya, MD, Patricia Mena , MD, Arna ldo Foradori, MD, Mario Becerra, MD, AIvaro Inzunza, MD, and A l f redo Germain, MD

From the Division of NeonataI-Perinatal Medicine, Departments of Pediatrics and Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, the Hospital Sot- ero del Rio, Puente Alto, Chile, and the Departments of Nuclear Medicine and of Obstetrics and Gynecology, Universidad Catolica de Chile, Santiago, Chile

We eva luated the response of preterm fetuses to maternal intravenous inject ion of 400 ~g of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before del ivery (n = 12). An addi t ional seven mothers received saline solution and served as control subjects. There were no statistically signif icant di f ferences in gestat ional age, birth weight, or Apgar scores between groups. At delivery, concentrat ions of maternal thyrotropin were e levated in the TRH group com- pared with the control group (12.0 _+ 1.6 vs 5.6 • 0.5 mU/L; p <0.005); however, maternal tr i iodothyronine (1'3) values remained unchanged. Significant eleva- tions of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 • 7.7 vs 8.4 • 0.9 mU/L [p <0.002] and 1.3 _+ 0.07 vs 0.7 _+ 0.04 nmol/L or 87 + 5 vs 49 �9 3 n g / d l (p <0.001], respective- ly). Fetal thyroxine (T4) and prolact in values were also e levated after exposure to TRH (135 • 5 vs 86 • 10 nmol/L or 10.5 • 0.4 vs 6.7 _+ 0.8 #g/d l [p <0.001] and 212 • 31 vs 105 • 28 ~g/L (p <0.05], respectively). Two hours after birth, a signif- icant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal admin- istration of this hormone results in marked stimulation of the preterm fetal pitu- itary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of Tz, (J PEDIATR 1991;119:966-71)

Thyrotropin releasing hormone crosses the placenta readily in laboratory animals and human beings.~4 Once in the fe-

tal circulation, TRH stimulates the release of thyrotropin

and prolactin by the fetal pituitary gland. We have reported

Presented in part at the Southern Society for Pediatric Research Meeting, New Orleans, La., Jan. 17-19, 1990 (published in abstract form: Clin Res 1990;38:48A and Pediatr Res 1990; 27:81A). Submitted for publication May 6, 1991; accepted June 21, 1991. Reprint requests: Fernando R. Moya, MD, Associate Professor of Pediatrics, Obstetrics, and Gynecology, Department of Pediatrics and Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-9063. 9/23/31953

that maternal administration of 400 ~g of TRH 2 hours be- fore cesarean section at term results in elevations of cord blood levels of thyrotropin and triiodothyronine. 4 A higher

dose of TRH (600/zg) achieved similar results. In that study

the postnatal surge of thyrotropin and T3 in term infants

RDS Respiratory distress syndrome T3 Triiodothyronine T4 Thyroxine TRH Thyrotropin releasing hormone

exposed to TRH before delivery was similar to that observed in control infants.

Recently, other effects of TRH in the fetus have received considerable attention. Fetal exposure to TRH seems to ac-

966

Page 2: Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

Volume 119 Effect o f prenatal TRH on fetal pituitary-thyroid axis 9 6 7 Number 6

celerate fetal lung maturation, especially when used in con- junction with glucocorticoids, s-7 The mechanisms for this interaction are still unclear. However, effects of TRH on surfactant secretion, alveolar protein leak, ontogeny of /3-adrenergic receptors, and fetal breathing have been described. 5-m Because of the potential effect of TRH on prevention of respiratory distress syndrome, its use in com- bination with glucocorticoids has been suggestedJ 1, z2

If TRH is used to prevent RDS, fetuses would be exposed to this hormone during the preterm period rather than at term. The fetal pituitary-thyroid axis undergoes substantial maturation during the second half of gestation. Fetal serum

levels of free T3 and thyroxine increase steadily from mid gestation to term, whereas fetal serum concentrations of

thyrotropin tend to reach a plateau or to decrease slightly after 30 weeks of gestation.13 The response to TRH has been examined in a small number of premature neonates. 14, 15

Their mean increment of thyrotropin was relatively close to that of term newborn infants.16 However, these studies were done at variable postnatal ages when significant changes in the pituitary-thyroid axis would have already occurred. Furthermore, whether in utero exposure to TRH interferes with the postnatal changes of thyrotropin and thyroid hor- mones in more immature neonates is not known. We there-

fore decided to conduct this study.

M E T H O D S

Pregnant women admitted to the Hospital Sotero del Rio, Puente Alto, Chile, in premature labor or about to undergo

cesarean section before 34 weeks of gestation were eligible for the study. After giving consent, women were injected intravenously with either 1 ml of isotonic saline solution, the diluent in the TRH preparation (control subjects, n = 7), or 400 #g of TRH (Thypinone), between 30 minutes and 5 hours before delivery (n = 12). The intravenous injection

was given slowly for several minutes while maternal vital signs, uterine contractility, and fetal heart rate were being monitored continuously. The dose of TRH, 400 #g, was based on our previous study showing no further stimulation of the fetal pituitary-thyroid axis with higher doses. 4

Hormonal determinations, Blood samples were collected from all women at the time of delivery, and from mixed umbilical cord blood because no significant arteriovenous umbilical cord differences have been noted for TSH, T3, and T4.17 Blood samples were also obtained at 2 hours after birth from all infants. The serum was separated quickly and fro- zen at - 2 0 ~ C until analysis. All serum samples were mea- sured at least in duplicate in the same assay. Determinations of thyrotropin, total T3, total T4, and prolactin were done by radioimmunoassay as previously described. 4

Statistical analysis, Statistical analysis was performed with paired and unpaired Student t tests. A p value of <0.05

Table I. Obstetric and neonatal data

Control group TRH ( n = 7) ( n = t 2 )

Gestational age (wk) 29.1 _+ 0.9 30.4 _+ 0.8 Range 26-34 26-34

Birth weight (kg) 1.36 _+ 0.33 1.61 + 0.14" Range 1.07-2.07 0.99-2.48

Presence of labor 7 11 Delivery by cesarean section 3 6 Apgar score at 5 rain <5 1 0 Mechanical ventilation 2 3

*p= 0.13.

was considered significant. All values correspond to

mean _+ SEM. This study was approved by the human investigation

committees of the participating institutions.

R E S U L T S

Nineteen pregnant women and their newborn infants

were studied. There was one twin pregnancy in the TRH group. No significant side effects were observed during or after the slow intravenous injection of TRH. Table I shows

a comparison of several obstetric and neonatal variables in the two groups. All women in the control group, and 11 of 12 women in the TRH group, were in preterm labor. No significant differences were observed in gestational age, de- livery by cesarean section, number of infants with low 5-minute Apgar score, or number of infants requiring me- chanical ventilation.

Maternal response to TRH. Deliveries were not elective; thus women given TRH received the injection between 30 minutes and 5 hours before delivery. Maternal thyrotropin concentration in the group injected with TRH was signif- icantly higher than in control subjects (12 .0_ 1.6 vs

5.6 _+ 0.5 mU/L; p <0.005), whereas no differences were observed in maternal T3 after the administration of TRH (3.4 + 0.I vs 3.1 -+ 0.2 nmol/L or 224 _+ 9 vs 206 +-+_ 16 ng/dl).

Fetal response to TRH (Table II). Among the control group, the mean fetal thyrotropin value was significantly higher than the maternal values (8.4 + 0.9 vs 5.6 +_ 0.5 mU/L; p <0.05). On the contrary, the mean fetal T3 value was much lower than the maternal concentrations (0.7 _+ 0.04 vs 3.1 + 0.2 nmol/L or 49 + 3 vs 206 _+ 16 ng/dl; p <0.01). Significant elevations of thyrotropin, T3, T4, and prolactin concentrations were observed after pre- natal exposure to TRH between 30 minutes and 5 hours before delivery. As a group, preterm fetuses exposed to TRH bad approximately a sixfold increase in thyrotropin values and a 75% increase in T3 values. However, if only those fetuses delivered 2 hours after maternal TRH admin-

Page 3: Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

9 6 8 Moya et al, The Journal of Pediatrics December 1991

CORD BLOOD TSH ( mUlL )

12o{ I

100~ I

I 8o! [

I

L 40!

2oh [- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

i . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 ~ l l L ! l[ ~ J A J- L

0 1 2 3 4 5 6 INTERVAL B E T W E E N TRH AND BIRTH ( hours )

Fig. t. Individual cord-blood values of thyrotropin (TSH) ([]) from fetuses exposed to TRH versus interval between ma- ternal TRH injection and birth. Mean values (+__2 SD) for control fetuses are plotted for comparison.

T a b l e II. Thyrotropin, T3, T4, and prolactin in cord blood and 2 hours after birth

Contro l va lues TRH

C o r d 2 Hr C o r d 2 Hr

ThyrotroPin (mU/L) 8.4 +_ 0.9 - - 45.8 _+ 7.7* - - T3 (nmol/L [ng/dl]) 0.7 +_ 0.04 (49 +_ 3) 1.2 +_ 0,1 (80 _+ 10)t 1.3 _+ 0,07 (87 _+ 5)* 2.0 _ 0.2 (134 _+ 14)~: T4 (nmol/L [~zg/dl]) 86 +_ 10 (6.7 _+ 0.8) 92 .+__ 5 (7.2 +- 0.4) 135 _+ 5 (10.5 +_ 0.4)* 122 _+ 5 (9.9 +_ 0.5) Prolactin (~zg/L) 105 _+ 28 - - 212 +_ 31w - -

*p <0.002 by unpaired t test versus control cord values. tp = 0.01 by paired t test between cord and 2-hour values, ~p <0.005 by paired t test between cord and 2-hour values. w <0.05 by unpaired t test versus control cord values.

istration are considered (n = 5; Figs. 1 and 2), their thyro-

tropin level was elevated eightfold (66.5 +- 13.1 m U / L )

and the T3 level doubled (I.5 _+ 0.06 nmol /L or 101 +_ 4

ng/dl) . The influence of the interval between maternal

T R H administration and birth on fetal serum thyrotropin

and T3 concentrations is shown in Figs. 1 and 2. All fetal

serum thyrotropin values and 12 of 13 fetal T3 values were

elevated above control values after T R H stimulation up to

5 hours before delivery.

Significant increases of serum concentrations of T3 were

observed 2 hours after birth in all but one control infant and

in all neonates in the T R H group (Table II), No postnatal

changes of serum T4 were observed 2 hours after birth in

either the control group or the T R H group,

D I S C U S S I O N

Pregnancy has a marked influence on the maternal pitu-

itary-thyroid axis. Throughout gestation, total serum T3

and T4 concentrations increase, but after 20 weeks of ges-

tation the maternal thyrotropin concentration remains un-

changed.~3 The thyrotropin response to T R H does not seem

to be modified by pregnancy, but the prolactin response is

relatively lower, t8 In our previous study, T R H was admin-

istered to pregnant women at term whose babies were de-

livered by elective cesarean section without labor. 4 Signif-

icant increases of thyrotropin and prolactin were observed,

but no changes in serum T3 levels occurred up to 2 hours

after the T R H injection, In the present study, we evaluated

the response to T R H in a group of women with preterm

Page 4: Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

Volume 119 Effect o f prenatal TRH on fetal pituitary-thyroid axis 969 Number 6

CORD BLOOD T ( nrnol/L ) 3

2 -

1.5 ~-

0.5

0

r <>

<> r 0

1~ 0 0

0

O -- I ~ _ _ ~ I I ] I I _ _ L I l

0 1 2 3 4 5 6

INTERVAL BETWEEN TRH AND BIRTH ( hours ) Fig. 2. Individual cord-blood values of T3 (0) from fetuses exposed to TRH versus interval between maternal TRH in- jection and birth. Mean values (_+2 SD) for control fetuses are plotted for comparison.

pregnancies, of whom all but one were in labor. A signifi- cant increase in the maternal thyrotropin level was also seen

after TRH administration. Comparison of the magnitude of the maternal thyrotropin response between preterm and term pregnancies is not possible in this study because we determined thyrotropin values only at delivery, which occurred at a variable interval of time after TRH adminis- tration. In accordance with previous observations by us and other investigators, no changes in maternal serum T3 con- centrations were seen after TRH administration. 4' 19 It is

possible that the maternal T3 response to thyrotropin is de- creased during the second half of pregnancy and during la- bor, when baseline T3 values have risen above those of non- pregnant women. 19, 20

The placenta is impermeable to thyrotropin; during the

second and third trimesters of gestation, the fetal thyrotro- pin concentration is higher than the maternal values, as confirmed in this study. 2~ Cord blood values of thyrotropin in these preterm fetuses were somewhat higher than those which we reported previously for term fetuses (8.4 _+ 0.9 vs 4.8 _~_- 1.0 mU/L) . 4 Others also have reported higher fetal thyrotropin values at about 30 weeks of gestation than at term. 2l Furthermore, higher cord blood thyrotropin con- centrations in infants born vaginally, in comparison with concentrations in those delivered by cesarean section, have been noted, z2 Thus the stimulus of labor and vaginal deliv-

ery might have contributed to a slightly higher cord blood

level of thyrotropin in our control group. In contrast, the

fetal T3 values were much lower than the maternal T3 val- ues among the control group. The human placenta is also relatively impermeable to T3 and T4, and maternal-fetal gradients of these hormones have been documented repeat- edly.4, 2l, 23 The lower fetal levels of thyroid hormone can be

partially explained by active conversion of T4 tO reverse T3, and of T3 to 3,3'-diiodothyronine by the placenta. 13, 24

During intrauterine life there is a progressive rise in the fe- tal T4 level from about mid gestation, followed by an increase in the fetal T3 level a few weeks later. 21 Our find-

ings are in general agreement with the reported increases of T3 and T4 levels during fetal development. 23, 25

Maternal administration of TRH before delivery resulted in elevations of serum thyrotropin, T3, T4, and prolactin levels in these preterm fetuses. The cord blood changes of thyrotropin and T3 observed 2 hours after maternal admin- istration of TRH are relatively similar to those we reported in term fetuses exposed to TRH for that same interval. 4 The postnatal thyrotropin response to TRH has also been shown to be of the same magnitude in preterm and term in- fants.14, 16

Healthy preterm infants have postnatal changes in thy- rotropin, T3, and T4 levels that are quantitatively smaller than those observed in term infants. 21, 26, 27 Furthermore,

among sick premature infants with RDS the early rise of the T 4 level may not be observed; however, T3 elevations do oc-

Page 5: Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

9 7 0 Moya et al. The Journal of Pediatrics December 1991

cur. 27 Even though the cord blood and 2-hour values of T3

were lower among control infants, the relative change in the

T3 value postnatally was similar in both groups of preterm

infants. No significant changes in the T4 value were seen in either group at 2 hours of age. However, most of the post-

natal changes in T4 values in term and preterm infants are observed around 24 hours after birth. 15, 21, z7 Although in

this study we did not determine the postnatal changes in

thyrotropin values, it appears that prenatal exposure to a

single dose of TRH does not interfere with normal postna-

tal changes in the pituitary-thyroid axis in preterm or term

infants. 4 However, repeated administration of TRH is as-

sociated with decreases in the thyrotropin response and in-

creased concentrations of thyroid hormones in human beingsY, 29

Recent studies of human subjects suggest that the com-

bined use of corticosteroids and TRH is more beneficial in

preventing and ameliorating RDS and its consequences than the use of corticosteroids alone) 2, 3o Although combi-

nation hormonal therapy may seem an attractive new ther-

apeutic modality, several questions remain. Perhaps one of

the most important is the significance of transient elevations

of fetal thyroid hormone levels brought about by TRH

stimulation during crucial periods of brain development.

The in utero increases of thyroid hormones as a result of maternal TRH administration are in the range of the phys-

iologic changes observed after birth in preterm and term

neonates. 21 This fact and the lack of long-term adverse ef-

fects among infants exposed to intraamniotic injection of a

large amount of T4 suggest that prenatal use of TRH to en-

hance fetal lung maturation is relatively safe) 1

We thank Dr. B. J. Green (Abbott Laboratories, North Chicago, Ill.) for supplying the TRH preparation, and the nurses and mid- wives of the Hospital Sotero del Rio, Puente Alto, Chile, for their assistance during the study.

R E F E R E N C E S

1. Roti E, Gnudi A, Braverman L, et al. Human cord blood con- centrations of thyrotropin, thyroglobulin, and iodothyronines after maternal administration of thyrotropin-releasing hor- mone. J Clin Endocr Metab 198l;53:813-7.

2. Melmed S, Harada A, Murata Y, et al. Fetal response to thy- rotropin-releasing hormone after thyroid hormone adminis- tration to the rhesus monkey: lack of pituitary suppression. Endocrinology 1979;105:334-41.

3. Devaskar U, Nitta K, Szewczyk K, Sadig F, deMello D. TranspiacentaI stimulation of functional and morphologic fe- tal rabbit lung maturation: effect of thyrotropin-releasing hor- mone. Am J Obstet Gyneeol 1987;157:460-4.

4. Moya F, Mena P, Heusser F, et al. Response of the maternal, fetal, and neonatal pituitary-thyroid axis to thyrotropin- releasing hormone. Pediatr Res 1986;20:982-6.

5. Rooney S, Marino P, Gobran L, Gross I, Warshaw J. Thyro- tropin-releasing hormone increases the amount of sur factant in lung lavage from fetal rabbits. Pediatr Res 1979;13:623-5.

6. Ikegami M, Jobe AH, Petenazzo A, Seidner SR, Berry DB, Ruffini L. Effects of maternal treatment with corticosteroids, T3, TRH, and their combinations on lung function of ventilated preterm rabbits with and without surfactant treatments. Am Roy Respir Dis 1987;136:892-8.

7. Warburton D, Parton L, Buckley S, Cosico L, Enns G, Saluna T. Combined effects of corticosteroid, thyroid hormones, and ~-agonist on surfactant, pulmonary mechanics, and/~-receptor binding in fetal lamb lung. Pediatr Res 1988;24:166-70.

8. Oulton M, Rasmusson MG, Yoon RY, Fraser M. Gestation- dependent effects of the combined treatment of glacocorticoids and thyrotropin-releasing hormone on surfactant production by fetal rabbit lung. Am J Obstet Gynecol 1989;160:961-7.

9. Tabor B, Ikegami M, Jobe AH, Yamada T, Oetomo SB. Dose response of thyrotropin-releasing hormone on pulmonary mat- uration in corticosteroid-treated preterm rabbits. Am J Obstet Gynecol 1990;163:669-76.

10. Umans JG, Umans HR, Szeto HH. Effects of thyrotropin-re- leasing hormone in the fetal lamb. Am J Obstet Gynecol 1986;155:1266-71.

11. Moya FR, Gross I. Prevention of respiratory distress syn- drome. Semin Perinatol 1988;12:348-58.

12. Morales WJ, O'Brien WF, Angel JL, Knuppel RA, Sawai S. Fetal lung maturation: the combined use of corticosteroids and thyrotropin-releasing hormone. Obstet Gynecol 1989;73: 111-6.

13. Fisher DA. Maternal-fetal thyroid function in pregnancy. Clin PerinatoI I983;i0:615-26.

14. Jacobsen BB, Andersen H, Dige-Petersen H, Hummer L. Pi- tuitary-thyroid responsiveness to thyrotropin-releasing hor- mone in preterm and small-for-gestational age newborns. Acta Paediatr Scand 1977;66:541-8.

15. Cuestas RA. Thyroid function in healthy premature infants. J PEDIATR 1978;92:963-7.

16. Jacobsen BB, Andersen H, Dige-Petersen H, Hummer L. Thyrotropin response to thyrotropin-releasing hormone in full term, euthyroid and hypothyroid newborns. Aeta Paediatr Scand 1975;65:433-8.

17. Penny R, Simms ME, Campbell WG, Spencer CA, Nicoloff JT. Thyroid indices in arterial and venous cord blood: signif- icantly greater levels of reverse triiodothyronine in venous blood than in arterial blood. Metabolism 1986;35:645-8.

18. Yl~korkala O, Kivinen S, Reinila M. Serial prolactin and thy- retropin responses to thyrotropin-releasing hormone through- out normal human pregnancy. J Clin Endocrinol Metab 1979; 48:288-92.

19. Miyamoto J. Prolactin and thyrotropin responses to thyrotro- pin-releasing hormone during the peripartal period. Obstet Gynecol 1984;63:639-44.

20. Harada A, Hershman JM, Reed AW, et al. Comparison of thyroid stimulators and thyroid hormone concentrations in the sera of pregnant women. J Clin Endocrinol Metab 1979;48: 793-7.

21. Fisher DA, Klein AH. Thyroid development and disorders of thyroid function in the newborn. N Engl J Med 1981 ;304:702- 12.

22. La o TT, Panesar NS. Neonatal thyrotropin and mode of de- livery. Br J Obstet Gynecol 1989;96:1224-7.

23. Fisher DA, Dussault JH, Sack J, Chopra IJ. Ontogenesis of hypothalamic-pituitary-thyroid function and metabolism in man, sheep, and rat. Recent Prog Horm Res 1977;33:59-116.

24. Roti E, Fang S, Green K, Emerson C, Braverman L. Human placenta is an active site of thyroxine and 3,3' ,5-triiodothyro-

Page 6: Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

Volume 119 Effect o f prenatal TRH on fetal pituitary-thyroid axis 9 7 1 Number 6

nine tyrosyl ring deiodination. J Clin Endocrinol Metab 198 I; 53:498-501.

25. Thorpe-Beeston JG, Nicolaides KH, Felton CV, Butler J, Mc- Gregor AM. Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus. N Engl J Med 1991;324:532-6.

26. Abbassi V, Merchant K, Abramson D. Postnatal triiodothyro- nine concentrations in healthy preterm infants and in infants with respiratory distress syndrome. Pediatr Res 1977;11: 802-4.

27. Klein AH, Foley B, Kenney FM, Fisher DA. Thyroid hormone and thyrotropin responses to parturition in premature infants with and without the respiratory distress syndrome. Pediatrics 1979;63:380-5.

28. Snyder P J, Utiger RD. Repetitive administration of thyrotro-

pin-releasing hormone results in small elevations of serum thyroid hormones and in marked inhibition of thyrotropin re- sponse. J Clin Invest 1973;52:2305-12.

29. Staub J J, Girard J, Mueller-Brand J, et al. Blunting of TSH response after repeated oral administration of TRH in normal and hypothyroid subjects. J Clin Endocrinol Metab 1978;46: 260-6.

30. Ballard RA, Ballard PL, Creasy R, Gross I, Padbury JP. Pre- natal thyrotropin-releasing hormone plus corticosteroid de- creases chronic lung disease in very low birth weight infants [Abstract]. Clin Res 1990;38:192A.

31. Barkai G, Zarfin Y, Ben-Harari M, Reichman B, Sack J, Mashiaeh S. In utero thyroxine therapy for the induction of fetal lung maturity: long-term effects. J Perinat Med 1988; 16:145-8.

Clinical and laboratory observations

Cerebrospinal fluid examination in symptom-free infants with risk factors for infection

Susan Fielkow, MD, Susan Reuter, RN, and Samuel P. Gotof f , MD

From the Department of Pediatrics, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois

Cerebrospinal fluid analysis is frequently performed on newborn infants as part of the evaluation for suspected

bacterial infection. It is important to identify newborn in- fants with meningitis, but the number with meningitis is less

than 3% of those evaluated, and lumbar puncture is asso-

ciated with some risk, as well as costJ' a In addition, there

is a high rate of unsuccessful or traumatic lumbar punc- tures.i~3

Increased attack rates of early-onset group B streptococ- cal infections 4 and early-onset infections in general 5 have

been clearly related to prolonged rupture of membranes and

chorioamnionitis. Attempts to identify infants with infec-

Presented at the meeting of the Midwest Society for Pediatric Re- search, Chicago, IlL, Nov. 2, 1990. Submitted for publication April 29, 1991; accepted June 17, 1991. Reprint requests: Samuel P. Gotoff, MD, Department of Pediat- rics, Rush Presbyterian-St. Luke's Medical Center, 1653 W. Con- gress Pkwy., Chicago, IL 60612.

9/24/31835

tions as early as possible has led to the practice of a "sepsis

workup" in symptom-free infants, based on the presence of

maternal risk factors such as chorioamnionitis. Although

bacteremia has been documented in symptom-free in- fants,6, 7 which may justify a blood culture, we questioned

the benefit of a CSF examination in addition to blood cul-

ture in symptom-free neonates and performed a retrospec-

tive chart review to answer the question.

See related article, p. 973.

I CSF Cerebrospinal fluid

M E T H O D S

The clinical and laboratory records accumulated during the 10-year period from 1978 to 1987 on all newborn infants from whom cerebrospinal fluid culture specimens were

taken within the first week of life were reviewed. The infants were either inborn or transferred to Rush Presbyterian-St.