Impact of Cesarean Section on Intermediate and Late Preterm Births: United States, 2000–2003

Authors

  • Michael H. Malloy MD, MS

    Corresponding author
    1. Michael H. Malloy is a Professor in the Department of Pediatrics at The University of Texas Medical Branch, Galveston, Texas, USA.
      Michael H. Malloy, MD, MS, Department of Pediatrics, The University of Texas Medical Branch, Waverly-Smith Pavilion, Room 6.104, 301 University Boulevard, Galveston, Texas 77555-0526, USA.
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  • These data were presented in part at the Annual Meeting of the Pediatric Academic Societies, Honolulu, Hawaii, May 5, 2005.

Michael H. Malloy, MD, MS, Department of Pediatrics, The University of Texas Medical Branch, Waverly-Smith Pavilion, Room 6.104, 301 University Boulevard, Galveston, Texas 77555-0526, USA.

Abstract

ABSTRACT: Background: Cesarean section appears to be associated with increased risk of neonatal mortality among infants of low-risk term pregnancies, but it may offer some survival advantage among the most extremely preterm infants. The impact on intermediate (32–33 wk) and late preterm (34–36 wk) deliveries remains uncertain. The objective of this analysis was to compare the neonatal mortality rate (death at 0–27 days), the mechanical ventilation usage rate, and the incidence of hyaline membrane disease among intermediate and late preterm infants delivered by primary cesarean section compared with those delivered vaginally.Methods: United States Linked Birth and Infant Death Certificate files from the years 2000 to 2003 were used. Maternal demographic characteristics, medical complications, and labor and delivery complications were abstracted from the files along with infant information. Because of concern for misclassification of gestational age, a procedure was used to trim away births in which the birthweight of an infant for a specific gestational age was inconsistent. Adjusted odds ratios were calculated using logistic regression for the risk of the three outcomes of interest relative to the mode of delivery.Results: A total of 422,001 live births were available with complete data from the trimmed data set (60% of untrimmed data). After adjustment by logistic regression for infant size at birth, birthweight, sex, Apgar score at 5 minutes less than 4, multiple births, breech presentation, presence of an anomaly, the presence of any maternal medical condition or complication of labor and delivery, labor induction, maternal race, age, education, and gravidity, the adjusted odds ratios (95% CI for neonatal mortality at gestational ages of 32, 33, 34, 35, and 36 wk) were, respectively, 1.69 (1.31–2.20), 1.79 (1.40–2.29), 1.08 (0.83–1.40), 2.31 (1.78–3.00), and 1.98 (1.50–2.62).Conclusions: These data suggest that for low-risk preterm infants at 32 to 36 weeks’ gestation, independent of any reported risk factors, primary cesarean section may pose an increased risk of neonatal mortality and morbidity. (BIRTH 36:1 March 2009)

The cesarean section rate in the United States continues to rise and preliminary data for 2006 report it to be 31.1 percent (1). This rate represents a 50 percent increase over the past 10 years. Among late preterm infants (34–36 week’s gestation), the cesarean rate in 2005 approached 33 percent and for infants at 32 to 33 weeks, the rate approached 40 percent (2). At the same time, the late preterm birth rate in the U.S. has increased 25 percent from 1990 to 2005, from 7.3 to 9.1 percent of live births. Late preterm infants have received an increasing amount of attention because of the large percentage of preterm births that they represent (72%), the fact that their number appears to be increasing and the fact that they consume many more health resources than normal term infants (3–6).

Recent reports also indicate that low-risk term infants delivered by primary cesarean section compared with vaginal delivery appear to be at higher risk for neonatal mortality (7,8). Although the delivery of extremely preterm infants at 22 to 25 weeks’ gestation by primary cesarean section may incur some survival advantage (9), the advantage of the procedure for intermediate and late preterm infants at 32 to 36 weeks’ gestation independent of known risk factors is not well reported in the literature (10,11).

The objective of this analysis was to determine whether or not primary cesarean section independent of known risk factors for a cesarean section offered any advantages for several outcomes among infants of intermediate and late preterm gestations. Only primary cesarean sections were examined because women who had previous cesarean sections are routinely operatively delivered in subsequent pregnancies, thus obscuring the risks that might dictate a cesarean section. Vaginal births after cesarean delivery were excluded from the comparison group.

Methods

United States Linked Birth and Infant Death Certificate files were obtained for the years 2000 to 2003 (12). These files contained maternal demographic characteristics, gravidity, medical complications of pregnancies, labor and delivery complications, labor induction, method of delivery, and infant characteristics. Demographic variables in the analysis included maternal race (Hispanic, non-Hispanic black, non-Hispanic white, and other), maternal age, and maternal education. Files were created using SAS software (13), which extracted all survivors and deaths of infants with a “best estimated gestational age” between 32 and 36 weeks.

The best estimated gestational age uses the recorded date of the last normal menses or a clinical estimate of gestational age if the latter appears inconsistent with infant birthweight (14). The algorithm for determining whether or not a birthweight should be considered inconsistent for a particular gestational age, however, has exceptionally large ranges for gestations less than 36 weeks (15). As a result, the inclusion of infants with birthweights that are inconsistent with a specific gestational age is observed frequently in analyses of vital statistics data. To examine a narrower spectrum of infants with birthweights that conformed more closely to the most frequently occurring birthweight within specific gestational age weeks, a trimming procedure was used to exclude infants with birthweights outside the mode plus or minus one-half the interquartile range of the distribution of birthweights for each of the weeks’ gestation examined (9). The number of records with all variables available for analysis after the trimming procedure, 422,001, represented 60 percent of the original 706,304 in the untrimmed data set.

Specific risk factors for cesarean section examined in this analysis included whether or not the pregnancy was a multiple birth, gravidity, whether or not the presentation was breech, whether or not a fetal anomaly was present, and whether or not a medical diagnosis or complication of labor and delivery was present and labor induction. The standard birth certificate lists 18 medical diagnoses and 16 complications of labor and delivery (see appendix of Malloy (9), for specific diagnoses and complications). The presence of one or more of the diagnoses or complications was recorded in an indicator variable for complications. Small-for-gestational-age (SGA) infants were considered as a potential risk for cesarean section. Infant size, SGA (< 10th percentile), appropriate for gestational age (AGA, 10th–90th percentile), or large for gestational age (LGA, > 90th percentile) was determined from examining the birthweight distributions of each weeks’ gestation by sex using the trimmed data set. An Apgar score at 5 minutes of less than 4 was considered as a proxy for a risk for which a cesarean section might have been performed because of an intrauterine asphyxiating event.

Chi-square tests for general association were used for nominal variables and Student t tests for comparing means of continuous variables. Logistic regression models were used to determine odds ratios and 95% confidence intervals comparing primary cesarean section with vaginal delivery for the primary outcome variables of neonatal mortality (death between birth and 27 days), the use of any mechanical ventilation, and the report of hyaline membrane disease after adjustment for potentially confounding factors. All analyses were carried out using SAS software (13). An arbitrary p value of 0.05 was designated to indicate statistical significance.

Results

Of the 422,001 live births, 1,754 neonatal deaths were available for analysis. The distribution of population characteristics by mode of delivery differed significantly for almost all characteristics examined (Table 1). Women who were white, older, and primiparous were more likely to be delivered by cesarean section than women who were black, young, and multiparous. More multiple pregnancies were delivered by cesarean section than singletons, and more women with medical and labor complications including breech presentations were delivered by cesarean section than those with uncomplicated deliveries. LGA infants were more likely to be delivered by cesarean section than appropriately sized infants, and infants delivered by cesarean section weighed less than those delivered vaginally (mean ± SD, 2,417 ± 423 g vs 2,613 ± 368 g).

Table 1. Percent Distribution of Maternal and Infant Characteristics by Mode of Delivery
CharacteristicVaginal (n = 309,150)Primary Cesarean Section (n = 112,851)p*
  • *

    p Value determined by chi-square test for general association for nominal variables and Student t test for continuous variables.

  • n.s. = not significant.

Maternal age (yr)
 < 185.73.0< 0.01
 18–3585.281.7 
 > 359.115.3 
Maternal education (yr)
 < 1223.333.1< 0.01
 1221.123.4 
 13–1632.829.4 
 > 1622.714.1 
Total pregnancies
 One34.536.5< 0.01
 Two or more65.563.5 
Multiple pregnancy
 No89.760.2< 0.01
 Yes10.339.8 
Race
 White59.468.2< 0.01
 Black23.117.9 
 Hispanic12.19.2 
 Other5.44.7 
Induction
 Yes17.610.4< 0.01
 No82.489.6 
Medical or labor complication
 Yes47.966.7< 0.01
 No52.133.3 
Breech presentation
 Yes1.430.5< 0.01
 No98.669.5 
Fetal anomaly present
 Yes0.40.4n.s.
 No99.699.6 
Apgar score at 5 min < 4
 Yes0.30.7< 0.01
 No99.799.3 
Male
 Yes53.351.9< 0.01
 No46.748.1 
Gestation (wk)
 325.211.9< 0.01
 337.814.6 
 3414.519.2 
 3525.424.3 
 3647.130.0 
Birthweight (g), mean ± SD2,613 ± 3682,417 ± 423< 0.01
Size for gestational age
 Appropriate82.781.7 
 Small8.13.0 
 Large9.215.3 
Neonatal mortality rate deaths per 1,000 live births2.674.61< 0.01

The primary cesarean section rate diminished from 45.4 percent at 32 weeks’ gestation to 18.9 percent at 36 weeks (Fig. 1). The overall neonatal mortality rate dropped from 11.6 per 1,000 live births at 32 weeks to 1.8 per 1,000 at 36 weeks with the raw relative risk of neonatal death among cesarean deliveries compared with vaginal deliveries running from 1.58 at 32 weeks’ gestation to 2.43 at 36 weeks (Fig. 2). The requirement for mechanical ventilation dropped from an overall rate of 16.7 percent at 32 weeks to 6.0 percent at 36 weeks, whereas the raw relative risk of mechanical ventilation among cesarean deliveries versus vaginal deliveries went from 1.45 at 32 weeks to 2.10 at 36 weeks (Fig. 3). The overall incidence of hyaline membrane disease ranged from 8.3 percent at 32 weeks to 1.14 percent at 36 weeks, and the raw relative risk for hyaline membrane disease comparing cesarean deliveries with vaginal deliveries went from 1.57 at 32 weeks to 2.00 at 36 weeks (Fig. 4).

Figure 1.

Cesarean section rates as a percentage of total births by gestational age, United States, 2000–2003 (trimmed data) (relative risk = cesarean section vs vaginal delivery).

Figure 2.

Neonatal mortality rates (0–27 days) per 1,000 live births for cesarean and vaginal deliveries by gestational age, United States, 2000–2003 (trimmed data) (relative risk = cesarean section vs vaginal delivery).

Figure 3.

Percentage of infants requiring any mechanical ventilation after cesarean or vaginal delivery by gestational age, United States, 2000–2003 (trimmed data) (relative risk = cesarean section vs vaginal delivery).

Figure 4.

Percentage of infants reported as having hyaline membrane disease after cesarean or vaginal delivery, United States, 2000–2003 (trimmed data) (relative risk = cesarean section vs vaginal delivery).

The top five causes of neonatal death by weeks’ gestation and mode of delivery were determined by tabulating the frequency of occurrence of International Classification of Diseases Codes-Revision 10 (ICD-10) (Table 2). The top cause of neonatal death for infants at weeks 32 to 36 for both cesarean and vaginal births was pulmonary hypoplasia (ICD-10 P280 or Q336), except for vaginal births at 35 weeks where trisomy 13 was the leading cause.

Table 2. Top Five Causes of Neonatal Mortality by Weeks’ Gestation and Method of Delivery
Top Five Causes of Neonatal Death by Gestation and Mode of Delivery
32 Weeks33 Weeks34 Weeks35 Weeks36 Weeks
Cesarean (n =194) (%)Vaginal (n =148) (%)Cesarean (n =192) (%)Vaginal (n =179) (%)Cesarean (n =154) (%)Vaginal (n =222) (%)Cesarean (n =155) (%)Vaginal (n =194) (%)Cesarean (n =144) (%)Vaginal (n =202) (%)
  1. Note. International Classification of Diseases—Revision 10 codes: antepartum hemorrhage = P021, NEC = P77, pulmonary hypoplasia = P280 or Q336, birth asphyxia = P219, bacterial sepsis = P369, hydrops fetalis not due to hemolytic disease = P832, hypoplastic left heart = Q234, heart malformation = Q249, renal agenesis = Q600–606, diaphragmatic hernia = Q790, multiple anomalies = Q897, anomalies unspecified = Q899, trisomy 13 = Q917, SIDS = R95, other unspecified causes = R99.

  2. n = number of deaths; NEC = necrotizing enterocolitis; SIDS = sudden infant death syndrome.

Pulmonary hypoplasia (17.5)Pulmonary hypoplasia (12.2)Pulmonary hypoplasia (12.0)Pulmonary hypoplasia (15.1)Pulmonary hypoplasia (13.0)Pulmonary hypoplasia (12.7)Pulmonary hypoplasia (10.3)Trisomy 13 (6.7)Pulmonary hypoplasia (12.2)Pulmonary hypoplasia (9.4)
Hydrops fetalis (5.6)NEC (5.4)Heart malformation (4.7)Trisomy 13 (5.0)Multiple anomalies (4.5)Trisomy 13 (6.8)Birth asphyxia (7.7)Anomalies unspecified (6.2)Birth asphyxia (10.5)SIDS (8.4)
Antepartum hemorrhage (4.6)Diaphragmatic hernia (5.4)Birth asphyxia (4.7)NEC (4.5)Heart malformation (4.5)Heart malformation (4.5)Antepartum hemorrhage (7.1)Diaphragmatic hernia (6.2)Antepartum hemorrhage (5.3)Hypoplastic left heart (6.9)
Bacterial sepsis (4.1)Trisomy 13 (4.1)Hydrops fetalis (4.2)Anomalies unspecified (3.4)Hypoplastic left heart (3.2)Diaphragmatic hernia (4.1)Hypoplastic left heart (4.5)Pulmonary hypoplasia (5.7)Anomalies unspecified (3.5)Trisomy 13 (5.0)
Heart malformation (3.6)Multiple anomalies (4.1)NEC (4.2)Multiple anomalies (3.4)Antepartum hemorrhage (3.2)NEC (4.1)Diaphragmatic hernia (2.6)SIDS (4.1)SIDS (2.6)Heart malformation (4.5)

Logistic regression was used to adjust the odds ratios for the three outcomes examined comparing primary cesarean section with vaginal delivery for the following variables: maternal race (non-Hispanic white, non-Hispanic black, Hispanic, and other), maternal age (< 18, 18–35, and > 35 yr), education (< 12, 12, 13–16, and > 16 yr), first pregnancy versus two or more pregnancies, presence of medical or labor complications (one or more vs none), multiple pregnancy (twins or higher vs singleton), induction (yes vs no), presence of a fetal anomaly (one or more vs none), infant sex, infant size (SGA, LGA, and AGA), and Apgar at 5 minutes less than 4. The adjusted odds ratio for neonatal mortality was significantly increased for cesarean section for every week examined except for 34 weeks (Table 3). At 34 weeks, the adjusted odds ratio was 1.08 (95% CI = 0.83–1.40). The adjusted odds ratio for mechanical ventilation was increased significantly for cesarean deliveries for every week examined, as were the adjusted odds ratios for hyaline membrane disease (Table 3).

Table 3. Adjusted Odds Ratios (95% CI) for Primary Cesarean Sections versus Vaginal Delivery for Neonatal Mortality and Morbidities by Weeks’ Gestation
Gestation (weeks) (N)Adjusted OR* (95% CI) (n)
Neonatal MortalityMechanical VentilationHyaline Membrane Disease
  • *

    Odds ratios adjusted for all maternal and infant characteristics listed in Table 1, including birthweight as a continuous variable.

  • N = total live births; n = number with neonatal mortality or morbidity.

32 (29,589)1.69 (1.31–2.20) (340)1.30 (1.21–1.40) (4,932)1.33 (1.20–1.46) (2,453)
33 (40,583)1.79 (1.40–2.29) (371)1.28 (1.19–1.36) (5,456)1.32 (1.21–1.45) (2,677)
34 (66,476)1.08 (0.83–1.40) (373)1.28 (1.20–1.36) (6,316)1.46 (1.34–1.60) (2,898)
35 (105,982)2.31 (1.78–3.00) (347)1.42 (1.33–1.51) (6,322)1.49 (1.36–1.64) (2,677)
36 (179,371)1.98 (1.50–2.62) (316)1.63 (1.53–1.73) (6,355)1.68 (1.50–1.88) (2,037)

Discussion

Late preterm infants have garnered increased attention over the past several years because of the increasing percentage of births that they represent and because of the additional costs of care they incur (3–6). It is not clear whether the increasing prevalence of these births is a function of a secular trend in increasing risks associated with these pregnancies requiring early delivery, changing obstetrical practices that call for early delivery due to altered perceptions of risk, or a more cavalier attitude toward the relatively low risks of mortality and morbidity that these infants pose and thus the perceived lack of need to postpone delivery. Whatever the reason, the increasing prevalence of delivery by cesarean section of these infants, based on this analysis, appears to add another level of risk for an adverse outcome after adjusting for several characteristics that might call for a cesarean section.

Few studies have reported the risk of neonatal mortality among infants at 32 to 36 weeks’ gestation by mode of delivery. Most studies have examined the impact of the mode of delivery relative to birthweight because of the greater perceived objectivity of the measurement of birthweight compared with gestational age and most have examined the impact only among very low–birthweight infants weighing less than 1,500 g at birth (16–18). Examining the issue relative to gestational age, however, offers a greater opportunity to understand the impact of development on outcome. Lee and Gould observed a greater risk of neonatal mortality among appropriately grown infants delivered by cesarean section from 32 to 36 weeks’ gestation and among SGA infants at 35 and 36 weeks’ gestation (11). However, they attributed this observation to their inability to control completely for the risks that might have been attributable to the reason for doing the cesarean section. Their analysis differed from the analysis presented here by the inclusion of repeat cesarean sections, which might well be considered an unrecorded risk factor for a subsequent cesarean section and a silent carrier of unrecorded risk unless taken into account in the analysis. The observation of increased risk associated with primary cesarean sections in this analysis of infants from 32 to 36 weeks’ gestation, and the report of a similar increased risk of neonatal mortality among term infants of low-risk pregnancies delivered by primary cesarean section, would seem to add support to the concept that increased risk might truly exist.

Late preterm infants have been recognized to be at increased risk for respiratory morbidities (3,5), and as this analysis points out, late preterm infants delivered by cesarean section are at higher risk for respiratory morbidity than infants delivered vaginally. The higher risk of respiratory morbidity for infants delivered by elective cesarean section than vaginally has been reported (19). The mechanism by which cesarean section puts an infant at higher risk for respiratory morbidity has been suggested to be associated with iatrogenic prematurity and disruption of the process of transitioning of the lung epithelial sodium channels to an active extrusion process that is somehow associated with the occurrence of labor and vaginal delivery (20). Although much of the respiratory morbidity, such as transient tachypnea of the newborn, reported in the literature is relatively benign and short lived, the morbidities reported in this analysis of the need for mechanical ventilation and the report of the occurrence of hyaline membrane disease suggest a more care intensive and costly hospital stay.

In examining the leading cause of neonatal death for both primary cesarean and vaginal births, the leading cause from 32 to 36 weeks’ gestation is pulmonary hypoplasia. In most cases, this leading cause exceeded the prevalence of the next leading cause by a factor of 2. The diagnosis of pulmonary hypoplasia or primary atelectasis associated with prematurity (ICD-10, P280) or pulmonary hypoplasia excluding those diagnoses associated with prematurity (ICD-10, Q336) is somewhat nebulous.

The question that arises is whether physicians, in the era of the availability of surfactant therapy, no longer consider it possible that these infants of later preterm births could be dying of hyaline membrane disease associated with surfactant deficiency. Thus, an infant dying of a respiratory cause must have a problem other than a straightforward surfactant deficiency. No neonatal deaths attributed to hyaline membrane disease were among the top 10 causes for either cesarean or vaginal births except at 34 weeks’ gestation, where hyaline membrane disease attains a ranking of the number 10 cause among cesarean births. If pulmonary hypoplasia is truly the predominant cause of neonatal death among infants of both cesarean and vaginal births from 32 to 36 weeks, what then might be the explanation for the mechanism by which primary cesarean delivery puts an infant at higher risk for neonatal mortality? Is pulmonary growth retardation (hypoplasia) in some obscure way causally related to the initiation of labor or the decision to deliver the infant by cesarean section? The occurrence of pulmonary hypoplasia would be something on which the mode of delivery should have little effect. Pulmonary hypertension that has been reported to be a morbidity or mortality risk among infants delivered by cesarean section did not appear among the top 10 causes of death for either cesarean section or vaginal delivery (21,22). Thus, examining the reported causes of neonatal death does not offer a ready explanation for why the risk of neonatal mortality appears to be increased among infants delivered by cesarean section.

For the outcomes of mechanical ventilation and hyaline membrane disease, a trend can be seen toward increasing risk of these morbidities among infants delivered by cesarean section as gestation progresses, particularly from 34 to 36 weeks’ gestation. This finding appears to be compatible with reports of the mechanisms by which cesarean section fails to affect a normal evolution of fluid clearance from the lungs (19,20). This effect becomes progressively more apparent in its impact as the maturity of the fetus increases.

This analysis has several potential limitations as a function of using vital statistics data. As addressed in the Methods section, the validity of the recorded gestational age may be in question because of dependence on last menstrual period dates for which the vast majority of gestational ages were based (95.4% in 2003) (13). Nevertheless, this analysis attempted to circumvent this problem by focusing on a much more restricted group of records with birthweights that fell well within published birthweight ranges for specific gestational ages (23). Information on maternal characteristics recorded in vital statistics data are relatively valid; however, medical, pregnancy, and labor complications may well be underreported (13). Thus, the appearance of an increased risk associated with cesarean section may reflect the effect of an unreported risk factor. The validity of the information on the use of mechanical ventilation is not known but is more likely to be underreported than overreported.

Conclusions

This analysis supports the concept that among infants delivered at 32 to 36 weeks’ gestation, an increased risk for neonatal mortality and morbidity exists among those delivered by primary cesarean section compared with vaginal delivery. The mechanism by which delivery by cesarean section increases the risk for neonatal mortality is not clear, but the particular morbidities examined suggest that the mechanism, at least for the morbidities, may be related to the impact of cesarean section on respiratory adaptation. Primary cesarean delivery of intermediate and late preterm infants should therefore be undertaken with caution.

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