effect of antenatal steroid administration on the fetal biophysical profile

3
Effect of Antenatal Steroid Administration on the Fetal Biophysical Profile Melinda K. Kelly, MD, 1 Elizabeth P. Schneider, MD, 1 Boris M. Petrikovsky, MD, PhD, 2 Martin L. Lesser, PhD 1 1 North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030 2 Nassau County Medical Center, 2201 Hempstead Turnpike, East Meadow, New York 11554 Received 30 November 1998; accepted 2 February 2000 ABSTRACT: Purpose. Our objective was to determine whether antenatal steroid administration affects the biophysical profile score in fetuses. Methods. A prospective study was conducted in 84 fetuses between 28 and 34 weeks’ menstrual age at risk of preterm delivery. Two intramuscular injections of 12 mg of betamethasone were given to the mother 24 hours apart. All fetuses underwent biophysical pro- file testing prior to and between 24 and 48 hours after steroid administration. Biophysical profiles (including nonstress tests) were evaluated by two maternal-fetal medicine specialists blinded to the timing of steroid administration. Neonatal outcome, including Apgar score, menstrual age at delivery, admission to and length of stay in the neonatal intensive care unit, and mortality, was analyzed in all subjects. Results. In 31 (37%; 95 confidence interval, 26.6– 47.2%) of 84 cases, the biophysical profile score de- creased at least 2 points after steroid administration. The most commonly affected variables were fetal breathing and the nonstress test. There was no sig- nificant difference in the neonatal outcome between the fetuses whose biophysical profile decreased and those whose did not. Conclusions. Biophysical profile scores were de- creased in more than one third of fetuses within 48 hours of antenatal steroid administration, but neona- tal outcome was not affected. Knowledge of this oc- currence could avoid incorrect decision making re- garding fetal well-being. © 2000 John Wiley & Sons, Inc. J Clin Ultrasound 28:224–226, 2000. Keywords: antenatal steroids; fetal biophysical pro- file; fetal assessment; Doppler ultrasonography T he biophysical profile is a widely accepted scoring system used in the antenatal assess- ment of fetal well-being. Several studies have demonstrated that the biophysical profile has a high sensitivity and specificity for the prediction of fetal outcome and fetal acid-base status. 1–5 The administration of certain medications to the mother has been shown to change the fetus’s biophysical profile score without having measur- able adverse effects on the fetus. 6 Mulder, Derks, and colleagues noted a transient reduction in fe- tal heart rate variability and the number of fetal body and breathing movements in 31 fetuses fol- lowing maternal betamethasone administration; however, umbilical Doppler studies performed be- fore and after steroid administration were un- changed. 7–9 If the fetal biophysical profile score changes after maternal steroid administration but the fetus is not compromised, incorrect deci- sion making regarding delivery might occur. The objective of this study was to determine whether antenatal steroid administration affects the bio- physical profile score in fetuses. PATIENTS AND METHODS Eighty-four fetuses between 28 and 34 weeks’ menstrual age at risk of preterm delivery were prospectively studied from April 1996 to Septem- ber 1997. Risk factors for preterm delivery in- cluded preterm labor, cervical incompetence, and placenta previa. Exclusion criteria included con- traindications to steroid administration, concur- rent maternal steroid use for medical indications, premature rupture of membranes, and fetal dis- tress. Approval was obtained from the institu- Correspondence to: B. M. Petrikovsky © 2000 John Wiley & Sons, Inc. 224 JOURNAL OF CLINICAL ULTRASOUND

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Page 1: Effect of antenatal steroid administration on the fetal biophysical profile

Effect of Antenatal Steroid Administration onthe Fetal Biophysical Profile

Melinda K. Kelly, MD,1 Elizabeth P. Schneider, MD,1 Boris M. Petrikovsky, MD, PhD,2

Martin L. Lesser, PhD1

1 North Shore University Hospital, 300 Community Drive, Manhasset, New York 110302 Nassau County Medical Center, 2201 Hempstead Turnpike, East Meadow, New York 11554

Received 30 November 1998; accepted 2 February 2000

ABSTRACT: Purpose. Our objective was to determinewhether antenatal steroid administration affects thebiophysical profile score in fetuses.

Methods. A prospective study was conducted in 84fetuses between 28 and 34 weeks’ menstrual age atrisk of preterm delivery. Two intramuscular injectionsof 12 mg of betamethasone were given to the mother24 hours apart. All fetuses underwent biophysical pro-file testing prior to and between 24 and 48 hours aftersteroid administration. Biophysical profiles (includingnonstress tests) were evaluated by two maternal-fetalmedicine specialists blinded to the timing of steroidadministration. Neonatal outcome, including Apgarscore, menstrual age at delivery, admission to andlength of stay in the neonatal intensive care unit, andmortality, was analyzed in all subjects.

Results. In 31 (37%; 95 confidence interval, 26.6–47.2%) of 84 cases, the biophysical profile score de-creased at least 2 points after steroid administration.The most commonly affected variables were fetalbreathing and the nonstress test. There was no sig-nificant difference in the neonatal outcome betweenthe fetuses whose biophysical profile decreased andthose whose did not.

Conclusions. Biophysical profile scores were de-creased in more than one third of fetuses within 48hours of antenatal steroid administration, but neona-tal outcome was not affected. Knowledge of this oc-currence could avoid incorrect decision making re-garding fetal well-being. © 2000 John Wiley & Sons,Inc. J Clin Ultrasound 28:224–226, 2000.

Keywords: antenatal steroids; fetal biophysical pro-file; fetal assessment; Doppler ultrasonography

The biophysical profile is a widely acceptedscoring system used in the antenatal assess-

ment of fetal well-being. Several studies havedemonstrated that the biophysical profile has ahigh sensitivity and specificity for the predictionof fetal outcome and fetal acid-base status.1–5

The administration of certain medications tothe mother has been shown to change the fetus’sbiophysical profile score without having measur-able adverse effects on the fetus.6 Mulder, Derks,and colleagues noted a transient reduction in fe-tal heart rate variability and the number of fetalbody and breathing movements in 31 fetuses fol-lowing maternal betamethasone administration;however, umbilical Doppler studies performed be-fore and after steroid administration were un-changed.7–9 If the fetal biophysical profile scorechanges after maternal steroid administrationbut the fetus is not compromised, incorrect deci-sion making regarding delivery might occur. Theobjective of this study was to determine whetherantenatal steroid administration affects the bio-physical profile score in fetuses.

PATIENTS AND METHODS

Eighty-four fetuses between 28 and 34 weeks’menstrual age at risk of preterm delivery wereprospectively studied from April 1996 to Septem-ber 1997. Risk factors for preterm delivery in-cluded preterm labor, cervical incompetence, andplacenta previa. Exclusion criteria included con-traindications to steroid administration, concur-rent maternal steroid use for medical indications,premature rupture of membranes, and fetal dis-tress. Approval was obtained from the institu-

Correspondence to: B. M. Petrikovsky

© 2000 John Wiley & Sons, Inc.

224 JOURNAL OF CLINICAL ULTRASOUND

Page 2: Effect of antenatal steroid administration on the fetal biophysical profile

tional review board prior to initiation of thestudy, and written informed consent was ob-tained from each mother.

Eligible women were given 2 intramuscular in-jections of 12 mg of betamethasone 24 hoursapart. (Injections were then repeated weekly ifindicated.) The fetal biophysical profile includingnonstress test was performed prior to and be-tween 24 and 48 hours after steroid administra-tion. The second biophysical profile was not usedfor clinical management. The ultrasound exami-nations were performed using an XP-120 ultra-sound scanner (Acuson, Mountain View, CA) with3.5-MHz linear and curvilinear tranducers. Thebiophysical profiles, including nonstress tests,were evaluated by two board-certified maternal-fetal medicine specialists blinded to the timing ofsteroid administration. Each of the 2 biophysicalprofiles was determined within the same 6-hourperiod of the day, to control for fetal diurnal varia-tions.10 The administration of other medications,including tocolytics, was not altered during thetesting interval.

The statistical objective was to estimate thepercentage of fetal examinations in which the sec-ond biophysical profile score decreased by at least2 points from the initial score. This percentagewas described using standard methods for calcu-lating 95% confidence intervals (95% CI) for pro-portions. Neonatal outcome was assessed by com-paring the number of admissions to the neonatalintensive care unit (NICU), length of stay in theNICU, menstrual age at delivery, Apgar score,and mortality between the neonates whose bio-physical profile scores decreased and those whosedid not. The Mann-Whitney test was used to com-pare the number of NICU admissions, length ofNICU stay, and menstrual age at delivery. Fish-er’s exact test was used to compare mortalityrates. A paired t-test was used to compare Apgarscores. A p value below 0.05 was considered sta-tistically significant.

RESULTS

Eighty-four pairs of biophysical profiles were ana-lyzed. The initial biophysical profile scores were10 out of 10 in 67 fetuses and 8 out of 10 in 17fetuses. Thirty-one (37%; 95% CI, 26.6–47.2%) ofthe 84 fetuses had a decrease in the biophysicalprofile score after steroid administration. Therewere 23 cases in which the biophysical profilescore decreased by 2 points (from 10 to 8 in 11cases and from 8 to 6 in 12 cases) and 8 cases inwhich it decreased by 4 points (from 10 to 6 in 3cases and from 8 to 4 in 5 cases). Thus, 5 fetuses

had a biophysical profile score of 4 after steroidadministration. No fetuses demonstrated a scoreof 0 or 2 after steroid administration. The mostcommonly affected variables were fetal breathing(18 cases) and the nonstress test (10 cases). In 3cases, fetal movements did not meet the criteriafor the 2-point biophysical profile component (thefetuses had <3 discrete body or limb movementsduring 30 minutes of observation). The amnioticfluid component of the biophysical profile was un-changed in all subjects. The fetuses with bio-physical profile score decreases of 4 points aftersteroid administration were retested within 24hours; all repeat biophysical profiles were nor-mal.

Of the 2 fetuses (2%) whose scores increased by2 points following steroid administration, 1 dem-onstrated fetal breathing not recorded in the bio-physical profile prior to steroid administration,and 1 gained points for reactivity on the nonstresstest. In the remaining 51 fetuses (61%), the bio-physical profile scores did not change.

Neonatal outcome was available for 80 (95%) of84 fetuses. As shown in Table 1, there were nosignificant differences in Apgar score, menstrualage at delivery, admission to the NICU, length ofNICU stay, or deaths between the neonateswhose biophysical profile score decreased aftersteroid administration and those whose did not.

There were 2 perinatal deaths, 1 due to meco-nium aspiration and the other to persistent fetalcirculation.

DISCUSSION

More than one third of the fetuses in our studyhad decreased biophysical profile scores after ste-

TABLE 1

Neonatal Outcome by Alteration in Biophysical Profile

Score Following Steroid Administration

Outcome Measured

Fetal Biophysical Profile Score

Increaseor No Change

(n = 53)Decrease(n = 31) p Value

Mean Apgar score1 minute 8.4 8.3 NS5 minutes 9.2 9.0 NS

Mean menstrual age atdelivery (weeks) 34.3 34.3 NS

Admission to NICU 32 21 NSMean length of NICU

stay (days) 15.7 16.5 NSPerinatal death 1 1 NS

Abbreviations: NS, not significant; NICU, neonatal intensive careunit.

ANTENATAL STEROIDS AND FETAL BIOPHYSICAL PROFILE

VOL. 28, NO. 5, JUNE 2000 225

Page 3: Effect of antenatal steroid administration on the fetal biophysical profile

roid administration, but there was no significantdifference in neonatal outcome between the fe-tuses whose biophysical profile score decreasedand those whose did not. It has been shown that anormal fetal biophysical profile score confers ahigh probability of perinatal survival and lack ofacidosis.2,5,11 Despite this information, no datahave been published regarding the reproducibili-ty of the biophysical profile score in normal fe-tuses. Without these data, a null hypothesis thatfetuses receiving antenatal steroids do not have achange in biophysical profile score could not beutilized in studies. Therefore, our statistical ob-jective was to determine the percentage of bio-physical profile scores that decreased after ste-roid administration. The obvious weakness of thistype of study design was our inability to have acontrol group that received a placebo instead ofsteroids, since steroid administration was thestandard of care.

Although 23 of the reductions in the biophysi-cal profile score were only by 2 points, the 4-pointreduction in 8 fetuses is greater than would beexpected to occur spontaneously in normal fe-tuses. Manning et al5 demonstrated a significantlinear correlation between biophysical profilescore and antepartum umbilical venous pH ob-tained by cordocentesis. It has also been demon-strated that a biophysical profile score of 6 or less,particularly when the components affected arethe nonstress test and fetal breathing, has a highpositive predictive value in predicting fetal dis-tress, admission to the NICU, and cumulativemorbid outcome.12–14 In our study, the most fre-quently affected biophysical profile componentsafter steroid administration were fetal breathingand the nonstress test. Nevertheless, there wasno significant difference in neonatal outcome be-tween those whose biophysical profile score de-creased and those whose did not. [However, weobserved no fetuses with extremely low biophysi-cal profile scores (0 or 2) after antenatal steroidadministration.] Thus, in the setting of recentlyadministered antenatal steroids, a borderline lowbiophysical profile score (4 or 6) may not be aspecific predictor of fetal distress. Knowledge ofthis may aid in decision making.

REFERENCES

1. Manning FA, Platt LD, Sipos L. Antepartum fetalevaluation: develoment of a fetal biophysical pro-file. Am J Obstet Gynecol 1980;136:787.

2. Manning FA, Morrison I, Harman CR, et al. Fetalassessment based on fetal biophysical profile scor-ing: experience in 19,211 referred hig-risk preg-nancies. Am J Obstet Gynecol 1987;157:880.

3. Vintzileos AM, Gaffney SE, Salinger LM, et al. Therelationship between fetal biophysical profile andcord pH in patients undergoing cesarean sectionbefore the onset of labor. Obstet Gynecol 1987;70:196.

4. Manning FA, Harman CR, Morrison I, et al. Fetalassessment based on fetal biophysical profile scor-ing. III. Positive predictive accuracy of the veryabnormal test (biophysical profile score 4 0). Am JObstet Gynecol 1990;162:398.

5. Manning FA, Snijders R, Harman CR, et al. Fetalbiophysical profile score. VI. Correlation with an-tepartum umbilical venous fetal pH. Am J ObstetGynecol 1993;169:755.

6. Paceman AM, Meyer BA, Thorp JA, et al. The ef-fect of magnesium sulfate tocolysis on the fetal bio-physical profile. Am J Obstet Gynecol 1989;161:771.

7. Mulder EJ, Derks JB, Zonneveld MF, et al. Tran-sient reduction in fetal activity and heart ratevariation after maternal betamethasone adminis-tration. Early Hum Dev 1994;36:49.

8. Derks JB, Mulder EJ, Visser GH. The effects ofmaternal betamethasone administration on the fe-tus. Br J Obstet Gynaecol 1995;102:40.

9. Cohlen BJ, Stinger RH, Derks JB, et al. Absence ofsignificant hemodynamic changes in the fetus fol-lowing maternal betamethasone administration.Ultrasound Obstet Gynecol 1996;8:252.

10. Petrikovsky BM, Kaplan GP. Diurnal non-stresstest variations in healthy term fetuses. A call forevening appointments for fetal testing. Early HumDev 1996;44:127.

11. Manning FA, Morrison I, Lange IR, et al. Fetalassessment based on fetal biophysical profile scor-ing: experience in 12,620 referred high-risk preg-nancies. I. Perinatal mortality by frequency andetiology. Am J Obstet Gynecol 1985;151:343.

12. Manning FA, Morrison I, Harman CR, et al. Theabnormal fetal biophysical profile score. V. Predic-tive accuracy according to score composition. Am JObstet Gynecol 1990;162:918.

13. Devoe LD, Youssef AA, Gardner P, et al. Refiningthe biophysical profile with a risk related evalua-tion of test performance. Am J Obstet Gynecol1992;167:346.

14. Petrikovsky BM. Fetal assessment: time to reas-sess. Ultrasound Obstet Gynecol 1999;67:237.

KELLY ET AL

226 JOURNAL OF CLINICAL ULTRASOUND