Trends in cesarean delivery at preterm gestation and association with perinatal mortality

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Trends in cesarean delivery at preterm gestation and association with perinatal mortality Cande V. Ananth, PhD, MPH; Anthony M. Vintzileos, MD OBJECTIVE: We sought to examine the extent to which a temporal in-

crease in preterm cesarean delivery is associated with gestational age– specific changes in perinatal survival in preterm gestations. STUDY DESIGN: We utilized data on singleton births in the United

States (1990 through 2004) delivered between 24-36 weeks’ gestation. Associations between changes in cesarean delivery at preterm gestations and trends in the risk of preterm stillbirth, and neonatal and perinatal mortality were estimated before and after adjustments for a variety of potential confounders. RESULTS: From 1990 through 2004, cesarean delivery rates increased

by 50.6%, 40.7%, and 35.8% at 24-27, 28-33, and 34-36 weeks, re-

spectively. The largest incremental effect of cesarean was associated with a reduction in stillbirths by 5.8%, 14.2%, and 23.1% at 24-27, 28-33, and 34-36 weeks, respectively, leading to an 11.4%, 4.9%, and 0.6% reduction in perinatal deaths at 24-27, 28-33, and 34-36 weeks, respectively. CONCLUSION: Increasing rates of preterm cesarean were associated

with improved perinatal survival. This association was evident largely because of dramatic incremental declines in stillbirths. Key words: cesarean section, neonatal mortality, preterm delivery, stillbirth, temporal trends.

Cite this article as: Ananth CV, Vintzileos AM. Trends in cesarean delivery at preterm gestation and association with perinatal mortality. Am J Obstet Gynecol 2011;204:505.e1-8.

T

he recent decade has witnessed a dramatic increase in the rate of cesarean delivery in most industrialized societies. The rate of cesarean delivery in the United States (32% in 20071) has increased by ⬎50% over the last decade,2 with consequent decline in the rate of From the Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, NJ (Dr Ananth), and the Department of Obstetrics and Gynecology, Winthrop-University Hospital, Mineola, NY (Dr Vintzileos). Presented, in part, at the 30th Annual Meeting of the Society for Maternal-Fetal Medicine, Chicago, IL, Feb. 1-6, 2010. Received Nov. 18, 2010; revised Jan. 4, 2011; accepted Jan. 31, 2011. Reprints: Cande V. Ananth, PhD, MPH, Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 125 Paterson St., New Brunswick, NJ 08901-1977. [email protected]. 0002-9378/$36.00 © 2011 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2011.01.062

vaginal birth following a previous cesarean.3 Such increases in cesarean delivery have been observed in both low-risk4 and high-risk populations, including among women who delivered very low birthweight (⬍1500 g)5 and macrosomic infants,6 breech presentations,7 multiple births,8,9 and in pregnancies with an array of maternal and fetal indications for cesarean.10,11 Concurrent with an increase in cesarean deliveries is the temporal increase in the rate of preterm births in the United States and most other industrialized countries.12-14 Obstetrical interventions at preterm gestational ages are performed in the setting of impending fetal compromise (or maternal indications warranting such interventions), and these interventions include either a labor induction or a prelabor cesarean or both. The increase in preterm births in the United States has occurred with a concurrent temporal increase in the rate of indicated preterm births. For instance, from 1989 through 2000, indicated preterm births at ⬍37 weeks among singleton gestations in the United States increased by approximately 50%.12,15 In fact, some investigators have interpreted the increasing preterm birth rate to be

linked to the increase in cesarean deliveries.16 Despite these general trends, however, the extent to which temporal changes in cesarean delivery, especially at preterm gestations, are associated with gestational age–specific changes in perinatal mortality remain poorly understood. We evaluated temporal changes in cesarean deliveries at preterm gestations in the United States, and investigated the extent to which such changes are associated with changes in preterm stillbirth and perinatal mortality rates. We carried out this study in a large populationbased setting of singleton preterm births in the United States from 1990 through 2004.

M ATERIALS AND M ETHODS We utilized the US-linked natality and infant deaths data files composed of births from 1990 through 2004, and the corresponding fetal death files for the same period. These data files correspond to data abstracted from birth certificates of live-born infants and from fetal and infant death certificates and assembled by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention.17 Infant deaths

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FIGURE 1

Cesarean delivery rates at preterm gestations

Temporal changes in preterm cesarean delivery and preterm primary and repeat cesarean deliveries (left ) and relative change in corresponding rates since 1990 (right ): United States, 1990 through 2004. Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

from 1992 through 1994 were not linked to the corresponding live births. Gestational age, reported in completed weeks, was based on menstrual dates. In about 5% of births that did not contain a valid date for the menstrual period, or when the menstrual-based gestational age was incompatible with birthweight, a clinical estimate of gestation, also contained on these data files, was used instead.18 If a valid month and year of the last menstrual period was available but the day was missing, gestational age was imputed by the NCHS.18 The replacement of menstrual-based gestational age by a clinical estimate, as well as imputation of missing gestational age, was performed consistently by the NCHS for all years (1990 through 2004).

Statistical analysis The primary variable for analysis pertains to the “method of delivery” data contained on the birth certificates that included both primary and repeat cesarean deliveries. We examined changes (1990 through 2004) in cesarean delivery 505.e2

rates at preterm gestations grouped as 24-27, 28-33, and 34-36 weeks. We then estimated the extent to which changes in cesarean delivery rates from 1990 through 2004 were associated with changes in stillbirth and perinatal mortality rates over the same period. Perinatal mortality included stillbirths and neonatal deaths. This study was restricted to singleton pregnancies that ended at preterm (24-36 weeks) gestations. These preliminary analyses were followed by a multivariable adjustment for a variety of confounding factors. This was accomplished by fitting a series of log binomial regression models19 with mortality as the dependent variable and an indicator for period (1990 or 2004). In the first model, we estimated the crude change in mortality rates from 1990 (reference) through 2004. This was followed by a sequential adjustment for confounders (listed below) and, lastly, a model with confounders and an indicator for cesarean delivery. In all models,

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the indicator for period was the primary variable of interest, with risk ratio for mortality associated with period (denoting change in mortality rates from 1990 through 2004) expressed as a “relative change” in mortality. This was calculated as [exp(␤)⫺1]*100 where ␤ corresponds to the log risk ratio for the period effect (an indicator for year of birth coded 1 for 2004 and 0 for 1990). We estimated the associations of changes in preterm cesarean delivery on trends in stillbirth and perinatal mortality at preterm gestational ages overall, as well as in the absence of ischemic placental disease (IPD). We defined IPD as the presence of ⱖ1 of the following conditions: pregnancy-induced hypertension, small for gestational age (SGA), or placental abruption.20-23 The latter analysis was deemed necessary to evaluate if there are any variations in the effect of preterm cesareans on mortality according to the underlying pathophysiology or, possibly, indications for cesarean delivery. We defined SGA as newborns with birthweight ⬍10th centile for gestational age, with standards derived from all births in this study. The confounders considered for adjustment included maternal age (grouped as ⬍20, 20-24, 25-29, 30-34, 35-39, and ⱖ40 years), primiparity, single marital status, and maternal race (whites, blacks, and other races). In addition, to account for variations in cesarean delivery rates across states,24 we further adjusted the analyses for geographic region of birth. Geographic regions were classified as Northeast (Maine, New Hampshire, Vermont, Rhode Island, Massachusetts, Connecticut, New York, New Jersey, and Pennsylvania), Midwest (Michigan, Ohio, Illinois, Indiana, Wisconsin, Minnesota, Iowa, Missouri, North Dakota, South Dakota, Nebraska, and Kansas), South (Delaware, Maryland, District of Columbia, Virginia, West Virginia, North Carolina, South Carolina, Georgia, Florida, Kentucky, Tennessee, Alabama, Mississippi, Arkansas, Louisiana, Oklahoma, and Texas), and West (Montana, Idaho, Wyoming, Colorado, New Mexico, Arizona, Utah, Nevada, Washington, Oregon, California, Hawaii, and Alaska). The

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TABLE 1

Distribution of gestational age–specific rates of preterm cesarean delivery and preterm birth from 1990 through 2004 in United States Rates of preterm cesarean delivery, %

Change 1990 through 2004, % (95% CI)

Variable

1990

1995

2000

2004

Total birthsa

406,591

382,671

406,349

435,599

................................................................................................................................................................................................................................................................................................................................................................................

Preterm cesarean

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

30.8

34.8

40.2

46.4

50.6 (47.1–54.1)

28-33 wk

29.9

31.5

35.5

42.0

40.7 (39.1–42.5)

34-36 wk

23.5

22.6

25.3

31.9

35.8 (34.6–36.9)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Preterm primary cesarean

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

25.1

28.6

32.7

37.0

47.5 (43.5–51.6)

28-33 wk

22.1

23.7

26.1

30.0

35.5 (33.5–37.6)

34-36 wk

15.1

14.7

15.9

19.3

27.6 (26.2–29.1)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Preterm repeat cesarean

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

5.7

6.3

7.5

9.4

63.9 (53.7–74.9)

28-33 wk

7.7

7.8

9.4

12.0

55.6 (51.4–60.0)

34-36 wk

8.4

7.9

9.4

12.6

50.4 (48.1–52.8)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

CI, confidence interval. a

Singleton at 24-36 wk in gestation.

Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

choice of confounders was based on a conservative change of 10% between the unadjusted and the confounder-adjusted risk ratios. Missing data on confounders were estimated to be ⬍2%. We also derived the number needed to treat to provide an indication of the number of cesarean deliveries that need to be performed to prevent a stillbirth or perinatal death.25 Although the number needed to treat provides a causal interpretation regarding the relationship between cesarean delivery and mortality, we use this statistic purely as a measure to understand the associations better.

FIGURE 2

Perinatal mortality rates at preterm gestations

Temporal trends in stillbirth and neonatal mortality at preterm gestational ages (left ) and relative change in stillbirth and neonatal mortality rates at preterm gestational ages since 1990 (right ): United States, 1990 through 2004. Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

Sensitivity analysis We performed a sensitivity analysis to examine the effect of primary and repeat cesarean deliveries at preterm gestational ages on preterm stillbirth and perinatal mortality. Statistical analysis was accomplished using the SAS system (version 9.2; SAS Institute, Cary, NC). This study was approved by the institutional review board of University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ.

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TABLE 2

Distribution of gestational age–specific mortality rates at preterm gestations from 1990 through 2004 in United States Mortality rates (per 1000) Variable

1990

1995

2000

2004

Change 1990 through 2004, % (95% CI)

Preterm stillbirth

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

166.7

168.3

162.0

157.4

⫺5.6 (⫺9.3 to ⫺1.7)

28-33 wk

51.4

49.2

47.2

44.1

⫺14.2 (⫺17.5 to ⫺10.7)

34-36 wk

11.7

10.4

9.4

8.6

⫺26.0 (⫺29.6 to ⫺22.1)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Preterm early neonatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

157.4

122.1

114.5

108.0

⫺31.4 (⫺34.7 to ⫺27.8)

28-33 wk

22.2

17.2

16.3

14.6

⫺34.5 (⫺38.7 to ⫺29.9)

34-36 wk

4.4

3.4

2.9

2.7

⫺38.6 (⫺43.8 to ⫺32.9)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Preterm late neonatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

36.4

39.0

44.9

45.1

24.0 (12.0⫺37.2)

28-33 wk

6.7

5.4

5.2

5.2

⫺23.1 (⫺31.7 to ⫺13.4)

34-36 wk

1.3

1.3

1.3

1.3

3.8 (⫺16.6 to 11.0)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Preterm neonatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

188.0

156.3

154.2

148.3

⫺21.1 (⫺24.5 to ⫺17.6)

28-33 wk

28.8

22.5

21.4

19.6

⫺31.7 (⫺35.6 to ⫺27.6)

34-36 wk

5.7

4.7

4.2

3.9

⫺30.5 (⫺35.5 to ⫺25.2)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Preterm perinatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

24-27 wk

323.4

298.3

291.3

282.3

⫺12.7 (⫺15.0 to ⫺10.3)

28-33 wk

78.7

70.7

67.6

62.9

⫺20.1 (⫺22.6 to ⫺17.5)

34-36 wk

17.3

15.0

13.5

12.5

⫺27.4 (⫺30.3 to ⫺24.3)

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ................................................................................................................................................................................................................................................................................................................................................................................

Early and late neonatal mortality are defined as deaths between 0-6 and 7-27 days, respectively; perinatal mortality included stillbirths plus neonatal deaths. CI, confidence interval. Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

R ESULTS Temporal changes in preterm cesarean deliveries and perinatal mortality Temporal trends in rates of preterm cesarean delivery from 1990 through 2004 and the corresponding relative changes in rates with 1990 as the base period are shown in Figure 1. Relative to the rates in 1990, preterm cesarean delivery increased by 37% (25.5% in 1990 to 35.0% in 2004). This increase in preterm cesarean was greatest at 24-27 weeks (Table 1). There was an overall 20.2% decline in preterm stillbirths from 1990 through 2004 (Figure 2); however, the greatest decline occurred at 34-36 weeks (26.0% decline) (Table 2). A similar pattern of decline was observed for neonatal and perinatal deaths. 505.e4

We examined the independent contributions of preterm cesarean delivery on mortality, stratified on gestational age at delivery (Table 3). From 1990 through 2004, stillbirths declined by 5.8%, 14.2%, and 23.1% at 24-27, 28-33, and 34-36 weeks, respectively. Further adjustment for the temporal increase in cesarean deliveries at these gestational ages resulted in a 17.6% increase in stillbirths at 24-27 weeks, and a decline of 2.6% and 19.3% at 28-33 and 34-36 weeks, respectively. In other words, had the rate of cesarean delivery remained stable from 1990 through 2004, stillbirth rates would have actually increased by 17.6% at 24-27 weeks, and declined by 2.6% and 19.3% at 28-33 and 34-36 weeks, respectively. Thus, the largest incremental effect of cesarean delivery was associated with the reduction of stillbirths

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by 23.4%, 11.6%, and 3.8%, respectively, at 24-27, 28-33, and 34-36 weeks. This incremental effect of cesarean was also associated with a reduction in perinatal mortality rates by 11.4%, 4.9%, and 0.6% at 24-27, 28-33, and 34-36 weeks, respectively. We also estimated these aforementioned associations between preterm cesarean deliveries and perinatal mortality by restricting the analysis to pregnancies without IPD (Table 4). These analyses show that the incremental benefit of preterm cesarean deliveries were in fact stronger for stillbirths than for the overall population of births (Table 3).

Number of cesarean deliveries needed to prevent a perinatal death The number of preterm cesarean deliveries associated with a prevention of a

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TABLE 3

Contribution of increases in preterm cesarean delivery to gestational age–specific declines in preterm stillbirth and perinatal mortality from 1990 through 2004 in United States Change (%, 95% CI) in mortality rates from 1990 through 2004 Variable

24-27 wk

28-33 wk

34-36 wk

Preterm stillbirth

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

⫺5.6 (⫺9.3 to ⫺1.7)

⫺14.2 (⫺17.5 to ⫺10.7)

Change adjusted for confounders

⫺5.8 (⫺9.8 to ⫺1.7)

⫺14.2 (⫺17.7 to ⫺10.5)

⫺26.0 (⫺29.6 to ⫺22.1)

....................................................................................................................................................................................................................................................................................................................................................................... a

⫺23.1 (⫺27.2 to ⫺18.8)

.......................................................................................................................................................................................................................................................................................................................................................................

Plus adjustment for preterm cesarean

17.6 (13.0⫺22.3)

⫺2.6 (⫺6.6 to 1.6)

⫺19.3 (⫺23.6 to ⫺14.8)

.............................................................................................................................................................................................................................................................................................................................................................. b

⫺23.4%

Incremental effect of preterm cesarean

⫺11.6%

⫺3.8%

................................................................................................................................................................................................................................................................................................................................................................................

Preterm early neonatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

⫺31.4 (⫺34.7 to ⫺27.8)

⫺34.5 (⫺38.7 to ⫺29.9)

⫺38.6 (⫺43.8 to ⫺32.9)

Change adjusted for confounders

⫺33.1 (⫺36.6 to ⫺29.5)

⫺38.4 (⫺46.6 to ⫺33.9)

⫺46.5 (⫺55.7 to ⫺37.3)

Plus adjustment for preterm cesarean

⫺30.5 (⫺34.3 to ⫺26.6)

⫺42.4 (⫺46.4 to ⫺38.0)

⫺42.0 (⫺46.9 to ⫺36.7)

....................................................................................................................................................................................................................................................................................................................................................................... a ....................................................................................................................................................................................................................................................................................................................................................................... .............................................................................................................................................................................................................................................................................................................................................................. b

⫺2.6%

Incremental effect of preterm cesarean

⫹4.0%

⫺4.5%

................................................................................................................................................................................................................................................................................................................................................................................

Preterm late neonatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

24.0 (12.0-37.2)

⫺23.1 (⫺31.7 to ⫺13.4)

3.8 (⫺16.6 to 11.0)

Change adjusted for confounders

24.0 (11.0-37.4)

⫺22.1 (⫺31.2 to ⫺11.9)

⫺5.0 (⫺18.2 to 10.4)

Plus adjustment for preterm cesarean

19.4 (7.1-33.2)

⫺29.5 (⫺37.8 to ⫺20.1)

....................................................................................................................................................................................................................................................................................................................................................................... a .......................................................................................................................................................................................................................................................................................................................................................................

⫺11.2 (⫺23.7 to 3.3)

.............................................................................................................................................................................................................................................................................................................................................................. b

Incremental effect of preterm cesarean

4.6

7.4

6.2

................................................................................................................................................................................................................................................................................................................................................................................

Preterm neonatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

⫺21.1 (⫺24.5 to ⫺17.6)

⫺31.7 (⫺35.6 to ⫺27.6)

⫺30.5 (⫺35.5 to ⫺25.2)

Change adjusted for confounders

⫺23.0 (⫺26.5 to ⫺19.3)

⫺34.6 (⫺38.5 to ⫺30.3)

⫺33.5 (⫺38.6 to ⫺28.0)

Plus adjustment for preterm cesarean

⫺21.4 (⫺25.1 to ⫺17.6)

⫺39.4 (⫺43.1 to ⫺35.5)

⫺36.4 (⫺40.2 to ⫺30.3)

....................................................................................................................................................................................................................................................................................................................................................................... a ....................................................................................................................................................................................................................................................................................................................................................................... .............................................................................................................................................................................................................................................................................................................................................................. b

⫺1.6%

Incremental effect of preterm cesarean

⫹4.8%

⫹2.9%

................................................................................................................................................................................................................................................................................................................................................................................

Preterm perinatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

⫺12.7 (⫺15.0 to ⫺10.3)

Change adjusted for confounders

⫺13.6 (⫺16.0 to ⫺11.1)

⫺20.1 (⫺22.6 to ⫺17.5)

⫺27.4 (⫺30.3 to ⫺24.3)

....................................................................................................................................................................................................................................................................................................................................................................... a

⫺21.0 (⫺23.7 to ⫺18.3)

⫺26.4 (⫺29.6 to ⫺23.0)

⫺16.1 (⫺18.9 to ⫺13.2)

⫺25.8 (⫺29.1 to ⫺22.4)

.......................................................................................................................................................................................................................................................................................................................................................................

⫺2.2 (⫺4.9 to 0.6)

Plus adjustment for preterm cesarean

.............................................................................................................................................................................................................................................................................................................................................................. b

⫺11.4%

Incremental effect of preterm cesarean

⫺4.9%

⫺0.6%

................................................................................................................................................................................................................................................................................................................................................................................

Changes were estimated from fitting log binomial regression models. CI, confidence interval. a

Confounders included region of birth, maternal age, primiparity, single marital status, and maternal race; b increase in preterm cesarean delivery rate from 1990 through 2004 of 50.4% (Table 1) is associated with reduction of perinatal mortality rate at 24-27 wk, for instance, by 11.4%, after adjustment for variety of confounding factors.

Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

preterm stillbirth or perinatal death in 1990 and 2004 are contrasted in Figure 3. The number of preterm cesarean deliveries required to prevent 1 preterm stillbirth and perinatal death showed a steep increase (for both periods) with advancing gestational age. These data also show a benefit of preterm cesarean insofar as preventing a preterm stillbirth or perinatal death was greater in 2004 (at 24 weeks, the number of cesareans, on average, needed to prevent a stillbirth was

3.3, 95% confidence interval [CI], 3.1– 3.5) than in 1990 (4.6, 95% CI, 4.3– 4.9). Subanalysis based on primary and repeat cesarean deliveries and their association with stillbirth and perinatal mortality (not shown) were similar to those shown for all cesarean deliveries.

C OMMENT This large population-based study of singleton preterm births in the United States shows that the steep temporal increase in

preterm cesarean deliveries appears to be favorably associated with a concurrent decline in preterm stillbirth and early neonatal mortality. For instance, the increase in cesarean deliveries from 1990 through 2004 by 47.6% at 24-27 weeks, 31.7% at 28-33 weeks, and 28.9% at 34-36 weeks was associated with an 11.4%, 4.9%, and 0.6% decline in perinatal mortality rates at these gestational ages, respectively. This relatively increased benefit of increased preterm cesareans at early vs later gesta-

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TABLE 4

Contribution of increases in preterm cesarean delivery in absence of ischemic placental disease conditions to gestational age–specific changes in preterm stillbirth and perinatal mortality from 1990 through 2004 in United States Change (%, 95% CI) in mortality rates from 1990 through 2004 Variable

24-27 wk

28-33 wk

34-36 wk

Preterm stillbirth

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

13.5 (6.4-21.1)

15.5 (7.9-23.6)

Change adjusted for confounders

15.4 (7.7-23.5)

13.7 (5.8-22.2)

Plus adjustment for preterm cesarean

44.2 (35.0-54.1)

28.9 (20.8-39.0)

2.0 (⫺6.8 to 11.7)

....................................................................................................................................................................................................................................................................................................................................................................... a

5.5 (⫺4.1 to 16.1)

.......................................................................................................................................................................................................................................................................................................................................................................

13.1 (2.7-24.5)

..............................................................................................................................................................................................................................................................................................................................................................

Incremental effect of preterm cesarean

⫺28.8%

⫺15.2%

⫺7.6%

................................................................................................................................................................................................................................................................................................................................................................................

Preterm perinatal mortality

.......................................................................................................................................................................................................................................................................................................................................................................

Crude change

⫺9.3 (⫺14.7 to ⫺5.6)

⫺3.7 (⫺8.5 to 1.4)

⫺11.0 (⫺16.9 to ⫺4.6)

Change adjusted for confounders

⫺9.3 (⫺13.0 to ⫺5.5)

⫺5.8 (⫺10.8 to ⫺0.6)

⫺10.6 (⫺16.9 to ⫺3.8)

Plus adjustment for preterm cesarean

⫺0.2 (⫺4.3 to 4.0)

0.0 (⫺5.1 to 4.9)

⫺9.9 (⫺16.3 to ⫺3.1)

....................................................................................................................................................................................................................................................................................................................................................................... a ....................................................................................................................................................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................................................................................................................................

Incremental effect of preterm cesarean

⫺9.1%

⫺5.8%

⫺0.7%

................................................................................................................................................................................................................................................................................................................................................................................

Ischemic placental disease conditions included ⱖ1 of preeclampsia, small for gestational age birth, and placental abruption. Changes were estimated from fitting log binomial regression models. CI, confidence interval. a

Confounders included region of birth, maternal age, primiparity, single marital status, and maternal race.

Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

FIGURE 3

Analysis of “number-needed to treat”

Number of cesarean deliveries needed to prevent a stillbirth (left ) and a perinatal death (right ) by gestational age in 1990 and 2004. Number of cesarean deliveries needed to prevent a perinatal death at ⱖ35 weeks (right ) is not shown since this estimate is negative. Ananth. Trends in preterm cesarean and perinatal mortality. Am J Obstet Gynecol 2011.

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tions was supported by the analysis of number of preterm cesareans needed to prevent a death. Cesarean deliveries are generally performed in the presence of maternal highrisk conditions or impending fetal compromise.23 Getahun et al10 documented a substantial increase in the rate of primary cesarean delivery among women within the Kaiser Permanente Southern California hospital. They showed that the rate of primary cesarean deliveries among women with no underlying indications increased by 250% from 1991 through 1992 (0.8%) and 2007 through 2008 (2.8%) among white women and by 146% (1.1% in 1991 through 1992 and 2.7% in 2007 through 2008) among African American women. They also showed a substantial temporal increase in rates of primary cesarean (among all race-ethnicity groups) for breech, dystocia, fetal distress, and other medical or obstetrical indications.10 These general patterns fall well in line with other studies of cesarean trends among both lowrisk and high-risk women.8,9 A temporal increase in rates of repeat cesarean delivery is also evident. Men-

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www.AJOG.org acker et al26 reported that the rate of repeat cesarean deliveries in the United States increased by 11% from 1991 through 2002. Similar patterns of increase were seen among low-risk women (women with singleton term births with vertex presentations). Perhaps more impressive was an increase in the rate of cesarean deliveries among women with no indicated risk (low-risk women without any medical or obstetrical complications), with 3-7% of all primary cesarean deliveries in the United States estimated to have been performed in women with no indicated maternal or fetal risks. Studies evaluating the benefits of cesarean in relation to neonatal mortality have produced conflicting findings, however. Malloy27 reported that cesarean did not provide a survival advantage for very low birthweight infants delivered at 22-25 weeks’ gestation. MacDorman et al4 reported higher neonatal mortality rates in women with “no indicated risks” who underwent cesarean in contrast to women who were delivered vaginally. In fact, they reported a 2.9-fold increased risk of neonatal deaths among cesarean births in comparison to women who were delivered vaginally.4 These findings are a sharp contrast with other studies. Delivery of very low birthweight babies with breech presentation by primary cesarean was associated with lower risk of neonatal mortality in comparison to babies with vertex presentations.5 MacDorman et al28 estimated that the adjusted odds ratio for neonatal mortality was 1.69 (95% CI, 1.35–2.11) for cesareans with no labor complications or procedures in comparison to women with planned vaginal deliveries. This finding, in light of the impressive temporal increase in cesarean delivery, is important.

Implications of the findings Despite the overall benefits of preterm cesarean deliveries on preterm perinatal mortality (Table 3), the analysis of number of preterm cesarean deliveries needed to prevent a perinatal death provides additional insights. The relatively fewer number of preterm cesareans needed to avoid a perinatal death (3-4 in 1990 and 2004) at very early (24-25

weeks) than at later (34-36 weeks) gestations provides clues to the influences of a pure gestational age effect vs those due to underlying maternal chronic conditions that may prompt a cesarean. Deaths later in gestation (34-36 weeks) may be strongly influenced by maternal or fetal high-risk conditions that prompted the cesareans, with gestational age (34-36 weeks) being less important in determining mortality in comparison to earlier gestational ages (24-25 weeks). In fact, this was confirmed in an analysis where the incremental effect of cesarean at 34-36 weeks’ gestation on perinatal mortality was virtually absent among pregnancies without any diagnosis of pregnancy-induced hypertension, SGA, or abruption (Table 4). In contrast, deaths at early gestations may reflect a pure gestational age effect that is directly related to perinatal survival29 and unlikely the consequence of any underlying chronic conditions. It is likely that antepartum fetal surveillance techniques through the years may have helped improve perinatal outcomes. In addition, these surveillance techniques may have led to timing of obstetrical interventions (cesarean) and delivery. However, since fetal surveillance– without any intervention– cannot lead to changes in perinatal outcomes, it is very likely that the benefit of preterm cesarean deliveries on perinatal survival is real.

Limitations and biases of the data A limitation of the study pertains to the estimation of gestational age. Since gestational age was largely based on the menstrual estimate, errors in dating are likely to shift the gestational age distribution toward lower gestational ages,30,31 thereby classifying a fraction of term births as preterm. There is also a possibility of bleeding early in pregnancy often mistaken for delayed menses.32 Since our goal was to estimate temporal changes in cesarean delivery and perinatal mortality, errors in gestational age may have had little to no influence on our findings (assuming that such errors would have likely remained constant across the study years). Reporting of modes of delivery and other sociodemo-

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graphic characteristics in vital records is excellent,33 so potential biases from these attributes on our findings is also likely to remain minimal. Despite adjustments for a variety of confounding factors, the impact of residual confounding by factors likely to influence the obstetrical management of pregnancies remains. For instance, early in gestation, a cesarean is performed through an active management protocol that will include continuous monitoring, steroid use, resuscitation methods, and involvement of the neonatal intensive care unit personnel to improve perinatal survival. In contrast, for those with an expectant management, the decision to allow a vaginal delivery is likely given the expected low survival rate. Data on whether a cesarean was performed before or following the onset of labor, and whether a stillbirth occurred before or after a hospital admission, were unavailable. Some of the stillbirths may have occurred in the antepartum period or prior to the hospital admission; in these cases, where there is fetal death on hospital admission, there is decreased likelihood for cesarean delivery. Thus, our estimates of the beneficial effects of (preterm) cesarean on intrapartum stillbirths are likely underestimated.

Summary and conclusions In summary, this study among US singleton preterm births shows that, with respect to stillbirths, the incremental benefit of the increased preterm cesarean deliveries was inversely associated with gestational age; although it was associated with decreased stillbirth at all preterm gestational ages, the highest stillbirth reduction was observed in the very early preterm gestations (24-27 weeks). Insofar as neonatal mortality is concerned, the incremental effect of increased preterm cesarean deliveries was associated with decreased neonatal mortality only in the very early preterm gestations (24-27 weeks). In contrast, the increase in preterm cesarean deliveries was associated with small increases in neonatal mortality at later preterm gestations (28-33 and 34-36 weeks). This latter observation may have been directly influenced by a relative excess of the ma-

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ternal chronic and obstetrical high-risk conditions that may have prompted cesarean delivery. Research to understand the specific underlying maternal and fetal indications as well as an evaluation of the extent to which nonmedical or obstetrical conditions (eg, cesarean on maternal request, those performed for fear of litigation, or influence of individual or institutional policies) that warrant a cesarean at preterm gestations and their effects on stillbirth and neonatal mortality may be beneficial. Despite the beneficial effects of preterm cesarean on perinatal mortality, an assessment of the benefits (or harm) of preterm cesarean on infant morbidity would be a target worthy of investigation. f REFERENCES 1. Menacker F, Hamilton BE. Recent trends in cesarean delivery in the United States. NCHS Data Brief 2010:1-8. 2. Wylie BJ, Mirza FG. Cesarean delivery in the developing world. Clin Perinatol 2008;35:57182., xii. 3. Menacker F. Trends in cesarean rates for first births and repeat cesarean rates for low-risk women: United States, 1990-2003. Natl Vital Stat Rep 2005;54:1-8. 4. MacDorman MF, Declercq E, Menacker F, Malloy MH. Infant and neonatal mortality for primary cesarean and vaginal births to women with ”no indicated risk,” United States, 19982001 birth cohorts. Birth 2006;33:175-82. 5. Muhuri PK, MacDorman MF, Menacker F. Method of delivery and neonatal mortality among very low birth weight infants in the United States. Matern Child Health J 2006; 10:47-53. 6. Boulet SL, Alexander GR, Salihu HM. Secular trends in cesarean delivery rates among macrosomic deliveries in the United States, 1989 to 2002. J Perinatol 2005;25:569-76. 7. Lee HC, El-Sayed YY, Gould JB. Population trends in cesarean delivery for breech presentation in the United States, 1997-2003. Am J Obstet Gynecol 2008;199:59.e1-8. 8. Kontopoulos EV, Ananth CV, Smulian JC, Vintzileos AM. The influence of mode of delivery

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www.AJOG.org on twin neonatal mortality in the US: variance by birth weight discordance. Am J Obstet Gynecol 2005;192:252-6. 9. Smith GC, Shah I, White IR, Pell JP, Dobbie R. Mode of delivery and the risk of deliveryrelated perinatal death among twins at term: a retrospective cohort study of 8073 births. BJOG 2005;112:1139-44. 10. Getahun D, Strickland D, Lawrence JM, Fassett MJ, Koebnick C, Jacobsen SJ. Racial and ethnic disparities in the trends in primary cesarean delivery based on indications. Am J Obstet Gynecol 2009;201:422.e1-7. 11. Gregory KD, Curtin SC, Taffel SM, Notzon FC. Changes in indications for cesarean delivery: United States, 1985 and 1994. Am J Public Health 1998;88:1384-7. 12. 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. 13. Joseph KS, Kramer MS, Marcoux S, et al. Determinants of preterm birth rates in Canada from 1981 through 1983 and from 1992 through 1994. N Engl J Med 1998;339:1434-9. 14. Kramer MS, Platt R, Yang H, et al. Secular trends in preterm birth: a hospital-based cohort study. JAMA 1998;280:1849-54. 15. Ananth CV, Joseph KS, Demissie K, Vintzileos AM. Trends in twin preterm birth subtypes in the United States, 1989 through 2000: impact on perinatal mortality. Am J Obstet Gynecol 2005;193:1076-82. 16. Bettegowda VR, Dias T, Davidoff MJ, Damus K, Callaghan WM, Petrini JR. The relationship between cesarean delivery and gestational age among US singleton births. Clin Perinatol 2008;35:309-23, v-vi. 17. Taffel SM, Ventura SJ, Gay GA. Revised US certificate of birth–new opportunities for research on birth outcome. Birth 1989;16: 188-93. 18. Taffel S, Johnson D, Heuser R. A method of imputing length of gestation on birth certificates. Vital Health Stat 2 1982:1-11. 19. Spiegelman D, Hertzmark E. Easy SAS calculations for risk or prevalence ratios and differences. Am J Epidemiol 2005;162:199-200. 20. Ananth CV, Vintzileos AM. Maternal-fetal conditions necessitating a medical intervention resulting in preterm birth. Am J Obstet Gynecol 2006;195:1557-63.

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21. Ananth CV, Vintzileos AM. Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med 2006;19:773-82. 22. Ananth CV, Peltier MR, Kinzler WL, Smulian JC, Vintzileos AM. Chronic hypertension and risk of placental abruption: is the association modified by ischemic placental disease? Am J Obstet Gynecol 2007;197:273.e1-7. 23. Ananth CV, Vintzileos AM. Medically indicated preterm birth: recognizing the importance of the problem. Clin Perinatol 2008;35:53-67. 24. Ford J, Grewal J, Mikolajczyk R, Meikle S, Zhang J. Primary cesarean delivery among parous women in the United States, 1990-2003. Obstet Gynecol 2008;112:1235-41. 25. Altman DG. Confidence intervals for the number needed to treat. BMJ 1998;317: 1309-12. 26. Menacker F, MacDorman MF, Declercq E. Neonatal mortality risk for repeat cesarean compared to vaginal birth after cesarean (VBAC) deliveries in the United States, 19982002 birth cohorts. Matern Child Health J 2010;14:147-54. 27. Malloy MH. Impact of cesarean section on neonatal mortality rates among very preterm infants in the United States, 2000-2003. Pediatrics 2008;122:285-92. 28. MacDorman MF, Declercq E, Menacker F, Malloy MH. Neonatal mortality for primary cesarean and vaginal births to low-risk women: application of an ”intention-to-treat” model. Birth 2008;35:3-8. 29. Wilcox AJ, Skjaerven R. Birth weight and perinatal mortality: the effect of gestational age. Am J Public Health 1992;82:378-82. 30. Kramer MS, McLean FH, Boyd ME, Usher RH. The validity of gestational age estimation by menstrual dating in term, preterm, and postterm gestations. JAMA 1988;260:3306-8. 31. Savitz DA, Terry JW Jr, Dole N, Thorp JM Jr, Siega-Riz AM, Herring AH. Comparison of pregnancy dating by last menstrual period, ultrasound scanning, and their combination. Am J Obstet Gynecol 2002;187:1660-6. 32. Gjessing HK, Skjaerven R, Wilcox AJ. Errors in gestational age: evidence of bleeding early in pregnancy. Am J Public Health 1999;89:213-8. 33. DiGiuseppe DL, Aron DC, Ranbom L, Harper DL, Rosenthal GE. Reliability of birth certificate data: a multi-hospital comparison to medical records information. Matern Child Health J 2002;6:169-79.