Research
ajog.org
OBSTETRICS
The timing of administration of antenatal corticosteroids in women with indicated preterm birth Tracy M. Adams, DO; Wendy L. Kinzler, MD; Martin R. Chavez, MD; Anthony M. Vintzileos, MD OBJECTIVE: We sought to determine the timing of administration of
antenatal corticosteroids (AS) for indicated preterm births and to identify which indications are associated with the most optimal timing of administration. STUDY DESIGN: This was a retrospective cohort of patients who received AS in anticipation of indicated preterm birth from 2009 through 2012 at Winthrop University Hospital, Mineola, NY. Medical records of patients who received AS, as identified through the hospital pharmacy database, were reviewed. Patients were included if they had a singleton or twin gestation and they received AS for maternal or fetal indications. Women were excluded if they received AS for spontaneous preterm labor or preterm rupture of membranes. Maternal demographic and obstetrical characteristics were compared between those who received AS 7 days vs >7 days from delivery using parametric and nonparametric tests with relative
risks and 95% confidence intervals. P < .05 was considered significant. RESULTS: In all, 193 patients were included in this study. Median latency from AS administration to delivery was 9 days (range, 0e83); 93 patients (48%) received AS within 7 days of delivery. There were no significant differences between the 2 groups with regards to baseline maternal characteristics. Those delivering within 7 days of AS administration were more likely to have maternal vs fetal indications (84% vs 16%). CONCLUSION: Only 48% of patients with an indication for preterm birth
received AS within 7 days of its administration. AS appear to be more optimally timed in the presence of maternal rather than fetal indications. Key words: antenatal corticosteroids, decision to administer antenatal corticosteroids, indicated preterm birth, preterm birth, timing of antenatal corticosteroids
Cite this article as: Adams TM, Kinzler WL, Chavez MR, et al. The timing of administration of antenatal corticosteroids in women with indicated preterm birth. Am J Obstet Gynecol 2014;212:x.ex-x.ex.
P
reterm delivery occurs in 11.7% of all pregnancies in the United States and is a leading cause for perinatal morbidity and mortality.1 Approximately one third of all preterm births are medically indicated.2-4 Antenatal corticosteroids (AS) given to pregnant women at risk for preterm delivery 7 days from AS administration.10-13 Since many patients remain undelivered after AS administration, weekly AS administration will ensure delivery within a week. However, several studies have suggested that multiple weekly AS administration is associated with decreased birthweight, decreased head circumference, and increased risk of fetal adrenal suppression.14-18 As a result, repeat dosing is not recommended by American Congress of Obstetricians and Gynecologists with the exception of a single rescue course.19 Since it is axiomatic
to do no harm, correct timing of AS administration in women at risk for preterm birth is of paramount importance. Since more than half of the preterm births are spontaneous, we as well as other investigators have previously focused in the timing of AS steroids in the setting of threatened preterm labor with or without premature rupture of the membranes. Unfortunately, it was found that only 20-40% of women who are given AS for threatened spontaneous preterm delivery actually go on to deliver within 7 days.20,21 Indicated preterm birth is a significant contributor encompassing up to 40% of all preterm births based on US population statistics.4 Yet, the data regarding timing of AS administration in indicated preterm birth are scarce.20 Therefore, we undertook this retrospective study to determine the timing of AS administration in indicated preterm births and to identify the indications associated with the most optimal timing. We hypothesized that
MONTH 2014 American Journal of Obstetrics & Gynecology
1.e1
Research
Obstetrics
ajog.org
indicated preterm births have an increased frequency of AS administered within 7 days of delivery and optimal administration may depend on the indication for deliver (maternal vs fetal).
M ATERIALS
AND
M ETHODS
This was a retrospective cohort of patients who received AS in anticipation of indicated preterm birth from 2009 through 2012 at Winthrop University Hospital, Mineola, NY. Patients who received AS were identified through the hospital pharmacy database; their medical records were then reviewed to abstract the clinical data. This study was approved by the institutional review board. The primary outcome was to determine the proportion of patients receiving AS for suspected indicated preterm birth delivering within 7 days. The secondary outcome was to determine which indications for AS administration were more frequently associated with optimal timing of AS administration. Patients were included if they had a singleton or twin gestation and they received AS between 24-34 weeks’ gestation for maternal or fetal indications. Maternal indications included: preeclampsia, bleeding previa, or other maternal illness such as thrombotic thrombocytopenia purpura,
acute abdomen, and supraventricular tachycardia. Fetal indications included idiopathic intrauterine growth restriction (IUGR) (without preeclampsia), abnormal fetal Doppler, oligohydramnios, nonreassuring fetal status, or placental anomaly (including vasa previa and placental hemangioma). Exclusion criteria were patients with high-order multiples, those who received AS for a threatened spontaneous preterm delivery, and incomplete records (patients who either transferred from or delivered at an outside institution). Patients who received AS for suspected abruption who had vaginal bleeding and contractions were excluded from this review, as it is unclear whether this was due to spontaneous preterm labor or abruptio placentae. Our institution’s practice is to administer AS to women between 24-34 weeks’ gestation who are at risk for preterm delivery. A single rescue course is considered if the first dose of AS was given >14 days prior, and the current gestational age is 7 d, n [ 100
P value
Age, y
31.7 ( 5.5)
31.9 ( 5.4)
.8
White
49 (53%)
59 (59%)
.2
Black
25 (27%)
21 (21%)
.2
Other
19 (20%)
20 (20%)
.5
2 (1e7)
.5
Race
Gravidity
2 (1e12)
Prior preterm delivery
20 (22%)
12 (12%)
.04
Prior cesarean delivery
26 (28%)
22 (22%)
.2
History of chronic hypertension
17 (18%)
18 (18%)
.5
4 (4%)
6 (6%)
.3
Current tobacco use Gestational age at time of AS
30.4 ( 2.8)
30.4 ( 2.9)
1.0
Gestational age at delivery
30.7 ( 2.7)
34.7 ( 3.0)
< .01
Data expressed as n (%), median (range), and mean ( SD). AS, antenatal corticosteroids. Adams. Antenatal corticosteroids timing in indicated preterm birth. Am J Obstet Gynecol 2014.
1.e2 American Journal of Obstetrics & Gynecology MONTH 2014
of the primary provider, although all patients did receive maternal-fetal medicine consultation, who ultimately decided upon the timing of AS administration. The latency between administration of AS and delivery was defined as the number of days between the first dose and delivery. The patients were then categorized into 1 of 2 groups: optimal timing (those with a latency of 7 days) and suboptimal timing (those with a latency of >7 days). Patients who received a rescue course were analyzed in the suboptimal group. Variables reviewed included maternal age, race, gravidity/parity, gestational age at time of AS administration, number of doses of AS given, gestational age at delivery, history of preterm delivery, prior cesarean delivery, history of chronic hypertension, and indication for AS administration as recorded in the medical record. The optimal and suboptimal groups were then compared using the appropriate parametric and nonparametric tests. To ensure comparability with respect to the circumstances of care, between those with optimal vs suboptimal timing of AS administration, we used the comparability scoring system as proposed by Vintzileos et al.22 We used c2 testing to compare categorical data, Student t test was used to compare continuous data, and the Wilcoxon rank sum test was used to compare ordinal data. P < .05 was considered significant. Relative risks and 95% confidence intervals were calculated. Multivariable regression analysis was performed to calculate adjusted relative risks.
R ESULTS A total of 1031 patients were identified through the hospital pharmacy database as having received betamethasone from 2009 through 2012. In all, 838 patients were excluded (756 received AS for spontaneous preterm labor, 76 had incomplete records, and 6 had triplet gestations), leaving 193 patients available for review. The median latency from AS to delivery was 9 days (range, 0e83); 93 patients (48%) received AS within 7 days of delivery. There were no significant differences in maternal age, race, or gravidity between the 2 groups. Women with optimal timing had an earlier gestational age at delivery than those
Obstetrics
ajog.org with suboptimal timing (Table 1) and were more likely to have received AS for maternal indications rather than for fetal indications; this remained true after adjustment for maternal age, gravida, race, and smoking (Table 2). The majority of patients who received AS for maternal indications (60%) delivered within 7 days of administration, whereas the majority of patients who received AS for fetal indications (76%) delivered >7 days from administration (Table 3). The most common maternal indication for AS administration was preeclampsia (85%), and the most common fetal indication was IUGR with or without abnormal fetal Doppler studies (63%). The median latency for patients receiving AS for fetal indications was greater than that of women receiving AS for maternal indications: 21 (range, 0e78) vs 5 (range, 0e83) days, respectively (P < .001). Twentyenine (29%) patients who received AS with suboptimal timing went on to deliver at 7 d, n [ 100
n (%)
Relative risk (95% CI) Unadjusted
Adjusteda
Maternal
78 (84)
53 (53)
1.5 (1.3e1.9)
1.4 (1.2e1.6)
Preeclampsia
70 (76)
41 (41)
1.9 (1.4e2.4)
1.5 (1.3e1.7)
4 (4)
11 (11)
0.4 (0.1e1.2)
1.0 (0.8e1.4)
4 (4)
1 (1)
4.3 (0.5e38)
1.8 (1.2e2.7)
15 (16)
47 (47)
0.3 (0.2e0.6)
0.7 (0.6e0.8)
Bleeding previa Other
b
Fetal IUGR/abnormal Doppler
8 (9)
31 (31)
0.3 (0.1e0.6)
0.7 (0.6e0.8)
Oligohydramnios
2 (2)
7 (7)
0.3 (0.1e1.4)
0.7 (0.5e0.9)
Otherc
5 (5)
9 (9)
0.6 (0.2e1.7)
0.8 (0.6e.0)
CI, confidence interval; IUGR, intrauterine growth restriction. a
For maternal age, gravida, race, and smoking; b Includes maternal acute abdomen, maternal supraventricular tachycardia, and thrombotic thrombocytopenic purpura; c Includes nonreassuring fetal status and placental anomalies.
Adams. Antenatal corticosteroids timing in indicated preterm birth. Am J Obstet Gynecol 2014.
Our results are comparable to those of 2 recently published studies that evaluated the timing of AS administration.20,21 Vis et al20 found that 41% of patients who received AS for anticipated preterm delivery delivered within 7 days of its administration. Boesveld et al21 found that 45.4% of women who received AS for anticipated preterm labor delivered within 7 days. However, these 2 studies included both indicated and spontaneous preterm delivery in their cohorts of women with “anticipated preterm delivery,” whereas the focus of this study is solely on women with suspected indicated preterm delivery. We would expect AS to be better timed for patients with indicated preterm birth when compared to patients with
spontaneous preterm birth since practitioners have control over the timing of delivery. It is interesting that we found this to be true only when maternal indications existed for preterm delivery, with 60% of patients delivering within 7 days. However, when fetal indications existed, the timing of AS administration was the same as or worse than for patients with spontaneous preterm delivery, with only 24% of patients delivering within 7 days.20,21 Since the benefit of AS is so great to the preterm infant, many practitioners are eager to administer them if there is a chance that the patient may deliver preterm. Unfortunately, this leads to many patients receiving AS unnecessarily. Additionally, administration of AS without consideration of the timing
C OMMENT The main finding of this study is that only 48% of women who received AS for a suspected indicated preterm delivery actually delivered within 7 days of its administration. Of the patients with suboptimal timing, 78% delivered preterm and would have received benefit from more optimal timing. The patients who received AS within 7 days of delivery were more likely to have maternal indications for AS administration than fetal indications.
TABLE 3
Comparison of optimal vs suboptimal timing in patients who received antenatal corticosteroids for maternal vs fetal indications Maternal indication, n [ 131 Interval
n (%)
7 d
78 (60)
>7 d
53 (40)
Fetal indication, n [ 62 P value
Relative risk (95% CI)
15 (24)
< .001
1.6 (1.3e1.9)
47 (76)
< .001
0.6 (0.5e0.8)
CI, confidence interval. Adams. Antenatal corticosteroids timing in indicated preterm birth. Am J Obstet Gynecol 2014.
MONTH 2014 American Journal of Obstetrics & Gynecology
1.e3
Research
Obstetrics
leads to missed opportunities to achieve the maximal neonatal benefits. In this study, AS was more optimally timed when maternal vs fetal indications existed for its administration. More research is needed to establish the ideal timing to administer AS for fetal indications, especially in the setting of fetal growth restriction. ACKNOWLEDGMENT The authors wish to acknowledge Cande V. Ananth, PhD, MPH (Columbia University Medical Center Department of Obstetrics and Gynecology) for his statistical assistance with the multivariable regression analysis. No financial compensation was provided.
REFERENCES 1. Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2010-2011. 2013;131:548-58. 2. Carreno CA, Costantine MM, Holland MG, Ramin SM, Saade GR, Blackwell SC. Approximately one-third of medically indicated late preterm births are complicated by fetal growth restriction. Am J Obstet Gynecol 2011;204:263. e1-4. 3. Ananth CV, Vintzileos AM. Maternal-fetal conditions necessitating a medical intervention resulting in preterm birth. Am J Obstet Gynecol 2006;195:1557-63. 4. Ananth CV, Joseph KS, Oyelese Y, Demissie K, Vintzileos AM. Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000. Obstet Gynecol 2005;105:1084-91.
ajog.org 5. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50:515-25. 6. Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. BJOG 1990;97:11-25. 7. Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials 1972-1994. Am J Obstet Gynecol 1995;175: 322-35. 8. Ring AM, Garland JS, Stafeil BR, Carr MH, Peckman GS, Pircon RA. The effect of a prolonged time interval between antenatal corticosteroid administration and delivery on outcome in preterm neonates: a cohort study. Am J Obstet Gynecol 2007;196:457.e1-6. 9. Chandrasekaran S, Srinivas SK. Antenatal corticosteroid administration: understanding its use as an obstetric quality metric. Am J Obstet Gynecol 2014;210:143.e1-7. 10. Kuk JY, An JJ, Cha HH, et al. Optimal time interval between a single course of antenatal corticosteroids and delivery for reduction of respiratory distress syndrome in preterm twins. Am J Obstet Gynecol 2013;209:256. e1-7. 11. McEvoy C, Schilling D, Spitale P, Peters D, O’Malley J, Durand M. Decreased respiratory compliance in infants less than or equal to 32 weeks gestation delivered more than 7 days after antenatal steroid therapy. Pediatrics 2008;121:e1032-8. 12. Peaceman A, Bajaj K, Kumar P, Grobman WA. The interval between a single course of antenatal steroids and delivery and its association with neonatal outcomes. Am J Obstet Gynecol 2005;193:1165-9. 13. Wilms FF, Vis JY, Pattinaja DA, et al. Relationship between the time interval from antenatal
1.e4 American Journal of Obstetrics & Gynecology MONTH 2014
corticosteroid administration until preterm birth and the occurrence of respiratory morbidity. Am J Obstet Gynecol 2011;205:49.e1-7. 14. French NP, Hagan R, Evans SF, Godfrey M, Newnham JP. Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 1999;180:114-21. 15. Waffarn F, Davis EP. Effects of antenatal corticosteroids on the hypothalamic-pituitaryadrenocortical axis of the fetus and newborn: experimental findings and clinical considerations. Am J Obstet Gynecol 2012;207:446-54. 16. Guinn DA, Atkinson MW, Sullivan L, et al. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: a randomized controlled trial. JAMA 2001;286: 1581-7. 17. Kairalla AB. Hypothalamic-pituitary-adrenal axis function in premature neonates after extensive prenatal treatment with betamethasone: a case history. Am J Perinatol 1992;9:428-30. 18. Wapner RJ, Sorokin Y, Thom EA, et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol 2006;195:633-42. 19. ACOG Committee on Obstetric Practice. Antenatal corticosteroid therapy for fetal maturation. ACOG Committee opinion no. 475. Obstet Gynecol 2011;117:422-4. 20. Vis JY, Wilms FF, Kuin RA, et al. Time to delivery after the first course of antenatal corticosteroids. Am J Perinatol 2011;28:683-8. 21. Boesveld M, Heida K, Oudijk MA, Brouwers HA, Koenen SV, Kwee A. Evaluation of antenatal corticosteroid prescribing patterns among 984 women at risk for preterm delivery. J Matern Fetal Neonatal Med 2014;27:516-9. 22. Vintzileos AM, Ananth CV, Smulian JC. The use of a comparability scoring system in reporting observational studies. Am J Obstet Gynecol 2014;210:112-6.
ajog.org
OBSTETRICS
The timing of administration of antenatal corticosteroids in women with indicated preterm birth Tracy M. Adams, DO; Wendy L. Kinzler, MD; Martin R. Chavez, MD; Anthony M. Vintzileos, MD OBJECTIVE: We sought to determine the timing of administration of
antenatal corticosteroids (AS) for indicated preterm births and to identify which indications are associated with the most optimal timing of administration. STUDY DESIGN: This was a retrospective cohort of patients who received AS in anticipation of indicated preterm birth from 2009 through 2012 at Winthrop University Hospital, Mineola, NY. Medical records of patients who received AS, as identified through the hospital pharmacy database, were reviewed. Patients were included if they had a singleton or twin gestation and they received AS for maternal or fetal indications. Women were excluded if they received AS for spontaneous preterm labor or preterm rupture of membranes. Maternal demographic and obstetrical characteristics were compared between those who received AS 7 days vs >7 days from delivery using parametric and nonparametric tests with relative
risks and 95% confidence intervals. P < .05 was considered significant. RESULTS: In all, 193 patients were included in this study. Median latency from AS administration to delivery was 9 days (range, 0e83); 93 patients (48%) received AS within 7 days of delivery. There were no significant differences between the 2 groups with regards to baseline maternal characteristics. Those delivering within 7 days of AS administration were more likely to have maternal vs fetal indications (84% vs 16%). CONCLUSION: Only 48% of patients with an indication for preterm birth
received AS within 7 days of its administration. AS appear to be more optimally timed in the presence of maternal rather than fetal indications. Key words: antenatal corticosteroids, decision to administer antenatal corticosteroids, indicated preterm birth, preterm birth, timing of antenatal corticosteroids
Cite this article as: Adams TM, Kinzler WL, Chavez MR, et al. The timing of administration of antenatal corticosteroids in women with indicated preterm birth. Am J Obstet Gynecol 2014;212:x.ex-x.ex.
P
reterm delivery occurs in 11.7% of all pregnancies in the United States and is a leading cause for perinatal morbidity and mortality.1 Approximately one third of all preterm births are medically indicated.2-4 Antenatal corticosteroids (AS) given to pregnant women at risk for preterm delivery 7 days from AS administration.10-13 Since many patients remain undelivered after AS administration, weekly AS administration will ensure delivery within a week. However, several studies have suggested that multiple weekly AS administration is associated with decreased birthweight, decreased head circumference, and increased risk of fetal adrenal suppression.14-18 As a result, repeat dosing is not recommended by American Congress of Obstetricians and Gynecologists with the exception of a single rescue course.19 Since it is axiomatic
to do no harm, correct timing of AS administration in women at risk for preterm birth is of paramount importance. Since more than half of the preterm births are spontaneous, we as well as other investigators have previously focused in the timing of AS steroids in the setting of threatened preterm labor with or without premature rupture of the membranes. Unfortunately, it was found that only 20-40% of women who are given AS for threatened spontaneous preterm delivery actually go on to deliver within 7 days.20,21 Indicated preterm birth is a significant contributor encompassing up to 40% of all preterm births based on US population statistics.4 Yet, the data regarding timing of AS administration in indicated preterm birth are scarce.20 Therefore, we undertook this retrospective study to determine the timing of AS administration in indicated preterm births and to identify the indications associated with the most optimal timing. We hypothesized that
MONTH 2014 American Journal of Obstetrics & Gynecology
1.e1
Research
Obstetrics
ajog.org
indicated preterm births have an increased frequency of AS administered within 7 days of delivery and optimal administration may depend on the indication for deliver (maternal vs fetal).
M ATERIALS
AND
M ETHODS
This was a retrospective cohort of patients who received AS in anticipation of indicated preterm birth from 2009 through 2012 at Winthrop University Hospital, Mineola, NY. Patients who received AS were identified through the hospital pharmacy database; their medical records were then reviewed to abstract the clinical data. This study was approved by the institutional review board. The primary outcome was to determine the proportion of patients receiving AS for suspected indicated preterm birth delivering within 7 days. The secondary outcome was to determine which indications for AS administration were more frequently associated with optimal timing of AS administration. Patients were included if they had a singleton or twin gestation and they received AS between 24-34 weeks’ gestation for maternal or fetal indications. Maternal indications included: preeclampsia, bleeding previa, or other maternal illness such as thrombotic thrombocytopenia purpura,
acute abdomen, and supraventricular tachycardia. Fetal indications included idiopathic intrauterine growth restriction (IUGR) (without preeclampsia), abnormal fetal Doppler, oligohydramnios, nonreassuring fetal status, or placental anomaly (including vasa previa and placental hemangioma). Exclusion criteria were patients with high-order multiples, those who received AS for a threatened spontaneous preterm delivery, and incomplete records (patients who either transferred from or delivered at an outside institution). Patients who received AS for suspected abruption who had vaginal bleeding and contractions were excluded from this review, as it is unclear whether this was due to spontaneous preterm labor or abruptio placentae. Our institution’s practice is to administer AS to women between 24-34 weeks’ gestation who are at risk for preterm delivery. A single rescue course is considered if the first dose of AS was given >14 days prior, and the current gestational age is 7 d, n [ 100
P value
Age, y
31.7 ( 5.5)
31.9 ( 5.4)
.8
White
49 (53%)
59 (59%)
.2
Black
25 (27%)
21 (21%)
.2
Other
19 (20%)
20 (20%)
.5
2 (1e7)
.5
Race
Gravidity
2 (1e12)
Prior preterm delivery
20 (22%)
12 (12%)
.04
Prior cesarean delivery
26 (28%)
22 (22%)
.2
History of chronic hypertension
17 (18%)
18 (18%)
.5
4 (4%)
6 (6%)
.3
Current tobacco use Gestational age at time of AS
30.4 ( 2.8)
30.4 ( 2.9)
1.0
Gestational age at delivery
30.7 ( 2.7)
34.7 ( 3.0)
< .01
Data expressed as n (%), median (range), and mean ( SD). AS, antenatal corticosteroids. Adams. Antenatal corticosteroids timing in indicated preterm birth. Am J Obstet Gynecol 2014.
1.e2 American Journal of Obstetrics & Gynecology MONTH 2014
of the primary provider, although all patients did receive maternal-fetal medicine consultation, who ultimately decided upon the timing of AS administration. The latency between administration of AS and delivery was defined as the number of days between the first dose and delivery. The patients were then categorized into 1 of 2 groups: optimal timing (those with a latency of 7 days) and suboptimal timing (those with a latency of >7 days). Patients who received a rescue course were analyzed in the suboptimal group. Variables reviewed included maternal age, race, gravidity/parity, gestational age at time of AS administration, number of doses of AS given, gestational age at delivery, history of preterm delivery, prior cesarean delivery, history of chronic hypertension, and indication for AS administration as recorded in the medical record. The optimal and suboptimal groups were then compared using the appropriate parametric and nonparametric tests. To ensure comparability with respect to the circumstances of care, between those with optimal vs suboptimal timing of AS administration, we used the comparability scoring system as proposed by Vintzileos et al.22 We used c2 testing to compare categorical data, Student t test was used to compare continuous data, and the Wilcoxon rank sum test was used to compare ordinal data. P < .05 was considered significant. Relative risks and 95% confidence intervals were calculated. Multivariable regression analysis was performed to calculate adjusted relative risks.
R ESULTS A total of 1031 patients were identified through the hospital pharmacy database as having received betamethasone from 2009 through 2012. In all, 838 patients were excluded (756 received AS for spontaneous preterm labor, 76 had incomplete records, and 6 had triplet gestations), leaving 193 patients available for review. The median latency from AS to delivery was 9 days (range, 0e83); 93 patients (48%) received AS within 7 days of delivery. There were no significant differences in maternal age, race, or gravidity between the 2 groups. Women with optimal timing had an earlier gestational age at delivery than those
Obstetrics
ajog.org with suboptimal timing (Table 1) and were more likely to have received AS for maternal indications rather than for fetal indications; this remained true after adjustment for maternal age, gravida, race, and smoking (Table 2). The majority of patients who received AS for maternal indications (60%) delivered within 7 days of administration, whereas the majority of patients who received AS for fetal indications (76%) delivered >7 days from administration (Table 3). The most common maternal indication for AS administration was preeclampsia (85%), and the most common fetal indication was IUGR with or without abnormal fetal Doppler studies (63%). The median latency for patients receiving AS for fetal indications was greater than that of women receiving AS for maternal indications: 21 (range, 0e78) vs 5 (range, 0e83) days, respectively (P < .001). Twentyenine (29%) patients who received AS with suboptimal timing went on to deliver at 7 d, n [ 100
n (%)
Relative risk (95% CI) Unadjusted
Adjusteda
Maternal
78 (84)
53 (53)
1.5 (1.3e1.9)
1.4 (1.2e1.6)
Preeclampsia
70 (76)
41 (41)
1.9 (1.4e2.4)
1.5 (1.3e1.7)
4 (4)
11 (11)
0.4 (0.1e1.2)
1.0 (0.8e1.4)
4 (4)
1 (1)
4.3 (0.5e38)
1.8 (1.2e2.7)
15 (16)
47 (47)
0.3 (0.2e0.6)
0.7 (0.6e0.8)
Bleeding previa Other
b
Fetal IUGR/abnormal Doppler
8 (9)
31 (31)
0.3 (0.1e0.6)
0.7 (0.6e0.8)
Oligohydramnios
2 (2)
7 (7)
0.3 (0.1e1.4)
0.7 (0.5e0.9)
Otherc
5 (5)
9 (9)
0.6 (0.2e1.7)
0.8 (0.6e.0)
CI, confidence interval; IUGR, intrauterine growth restriction. a
For maternal age, gravida, race, and smoking; b Includes maternal acute abdomen, maternal supraventricular tachycardia, and thrombotic thrombocytopenic purpura; c Includes nonreassuring fetal status and placental anomalies.
Adams. Antenatal corticosteroids timing in indicated preterm birth. Am J Obstet Gynecol 2014.
Our results are comparable to those of 2 recently published studies that evaluated the timing of AS administration.20,21 Vis et al20 found that 41% of patients who received AS for anticipated preterm delivery delivered within 7 days of its administration. Boesveld et al21 found that 45.4% of women who received AS for anticipated preterm labor delivered within 7 days. However, these 2 studies included both indicated and spontaneous preterm delivery in their cohorts of women with “anticipated preterm delivery,” whereas the focus of this study is solely on women with suspected indicated preterm delivery. We would expect AS to be better timed for patients with indicated preterm birth when compared to patients with
spontaneous preterm birth since practitioners have control over the timing of delivery. It is interesting that we found this to be true only when maternal indications existed for preterm delivery, with 60% of patients delivering within 7 days. However, when fetal indications existed, the timing of AS administration was the same as or worse than for patients with spontaneous preterm delivery, with only 24% of patients delivering within 7 days.20,21 Since the benefit of AS is so great to the preterm infant, many practitioners are eager to administer them if there is a chance that the patient may deliver preterm. Unfortunately, this leads to many patients receiving AS unnecessarily. Additionally, administration of AS without consideration of the timing
C OMMENT The main finding of this study is that only 48% of women who received AS for a suspected indicated preterm delivery actually delivered within 7 days of its administration. Of the patients with suboptimal timing, 78% delivered preterm and would have received benefit from more optimal timing. The patients who received AS within 7 days of delivery were more likely to have maternal indications for AS administration than fetal indications.
TABLE 3
Comparison of optimal vs suboptimal timing in patients who received antenatal corticosteroids for maternal vs fetal indications Maternal indication, n [ 131 Interval
n (%)
7 d
78 (60)
>7 d
53 (40)
Fetal indication, n [ 62 P value
Relative risk (95% CI)
15 (24)
< .001
1.6 (1.3e1.9)
47 (76)
< .001
0.6 (0.5e0.8)
CI, confidence interval. Adams. Antenatal corticosteroids timing in indicated preterm birth. Am J Obstet Gynecol 2014.
MONTH 2014 American Journal of Obstetrics & Gynecology
1.e3
Research
Obstetrics
leads to missed opportunities to achieve the maximal neonatal benefits. In this study, AS was more optimally timed when maternal vs fetal indications existed for its administration. More research is needed to establish the ideal timing to administer AS for fetal indications, especially in the setting of fetal growth restriction. ACKNOWLEDGMENT The authors wish to acknowledge Cande V. Ananth, PhD, MPH (Columbia University Medical Center Department of Obstetrics and Gynecology) for his statistical assistance with the multivariable regression analysis. No financial compensation was provided.
REFERENCES 1. Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2010-2011. 2013;131:548-58. 2. Carreno CA, Costantine MM, Holland MG, Ramin SM, Saade GR, Blackwell SC. Approximately one-third of medically indicated late preterm births are complicated by fetal growth restriction. Am J Obstet Gynecol 2011;204:263. e1-4. 3. Ananth CV, Vintzileos AM. Maternal-fetal conditions necessitating a medical intervention resulting in preterm birth. Am J Obstet Gynecol 2006;195:1557-63. 4. Ananth CV, Joseph KS, Oyelese Y, Demissie K, Vintzileos AM. Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000. Obstet Gynecol 2005;105:1084-91.
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