Previous research has strongly suggested a relationship between gestational age at elective cesarean delivery and the risk of neonatal respiratory distress. This has led to the development of guidelines recommending elective cesarean delivery at term (39 weeks or later). Unfortunately, even adhering to these guidelines, it is anticipated that at least 4–5% of neonates will still develop signs of respiratory distress and require admission to neonatal intensive care units. Retrospective studies have also suggested that labor before caesarean delivery is associated with a lower rate of neonatal respiratory distress. The mechanism of this effect is unknown, but it is postulated to be secondary to activation of epithelial sodium channels in the fetal lung.1
Glucocorticoids appear to be a potent up-regulator of the expression of epithelial sodium channel genes2 and are secreted in increasing amounts by the fetal adrenal gland at term. Fetal hypothalamic-pituitary-adrenal axis maturation and adrenal glucocorticoid production are also felt to be possible triggers for the onset of labor at term.3,4 Thus, adrenal production of glucocorticoids may both initiate labor and prepare the fetus for extra-uterine life.
Therefore, it has been postulated that the rates of respiratory distress could be reduced further if elective cesarean delivery is delayed until the onset of labor or ruptured membranes.5 However, most of the studies that reported a protective effect of labor included women who had cesarean delivery after prolonged labor and not just women having an elective repeat cesarean delivery shortly after the onset of labor.6–9 Additionally, the few studies that have focused on women undergoing elective cesarean delivery were before the era of ultrasound dating of gestational age.10,11
Therefore, the lower rates of respiratory distress observed following cesarean delivery after the onset of labor may simply reflect that these fetuses were more likely to be truly at a term gestation. Ultimately, it is not clear whether the short duration of labor before elective repeat cesarean delivery is protective. The intent of our study was to estimate whether the risk of neonatal intensive care unit (NICU) admission and neonatal respiratory distress was lower in women undergoing cesarean delivery after spontaneous rupture of membranes or the onset of labor. We had planned this study to determine the feasibility of conducting a clinical trial to evaluate the effectiveness of awaiting labor or ruptured membranes before elective cesarean delivery in reducing NICU admission and neonatal respiratory distress. Additionally, we wished to confirm the relationship between gestational age at cesarean delivery and risk of respiratory distress in our population.
MATERIALS AND METHODS
This was a chart review of all elective cesarean deliveries done in the Calgary Health Region, Calgary, Alberta, Canada, within one fiscal year from March 1, 2004, to April 30, 2005. There were 13,360 deliveries in Calgary, occurring in three obstetric units during the study year, and cesarean deliveries accounted for 26.4% of the deliveries. Charts were identified through Quality Safety and Health Information based on the criteria of delivery of a liveborn infant with a gestational age of 37 weeks or more or 2,500 g or more birth weight and delivered by elective cesarean delivery. Elective cesarean was defined as a documented planned cesarean delivery with no intention for a vaginal delivery and included deliveries occurring after onset of labor or rupture of membranes, but already booked for cesarean delivery.
Information abstracted from the maternal chart included age, gravidity, parity, antepartum risk factors, intrapartum factors including rupture of membranes, presence of contractions, and duration of labor, antepartum or intrapartum maternal medications, postpartum complications, and length of stay. An obstetrician reviewed the obstetric data and calculated the gestational age at delivery based on the last menstrual period and ultrasound reports, if available. Labor before cesarean delivery was defined as the presence of symptomatic contractions or rupture of membranes before cesarean delivery.
Data abstracted from the infant chart included birth weight, gender, Apgar scores, cord pH, resuscitation parameters, treatment provided if admitted to NICU, diagnoses, and length of stay. In the case of twin pregnancies, to avoid the confounding effect of potential higher morbidity risk in the second twin, only the first-born twin was entered into the study. A neonatologist, blinded to the maternal data, reviewed the neonatal data and confirmed assignment of respiratory distress based on prespecified definitions and admission to NICU.
Respiratory distress in this study was clinically defined as signs inclusive of tachypnea, with respiratory rate of more than 60 breaths per minute, retractions, grunting, nasal flaring, and cyanosis in room air, or requiring treatment with any of the following: supplemental oxygen, nasal continuous positive airway pressure, endotracheal intubation, or exogenous surfactant.
Univariable analysis was performed with χ2 test for categorical data and Student t test for continuous data to identify significant obstetric and neonatal characteristics associated with NICU admission and respiratory distress. P<.05 was considered significant. Multivariable logistic regression was used to control for potential confounding factors. A nonparametric scatterplot smoother (locally weighted scatterplot smoothing, LOWESS) was also used to examine the form of the relationship between gestational age and neonatal respiratory distress. The sample size estimated for this study was based on an expected 5% NICU admission rate in the neonates delivered after labor compared with a 13% admission rate in the no-labor group. By our calculations, with a 1-year sample of cases (n=1,200), our study would have over 80% power to detect a 50% difference in the rates of NICU admission.
Statistical analyses were performed with Stata 9.2 (Stata Corp, College Station, TX). The study was approved by the Conjoint Health Research Ethics Board of the Faculty of Medicine of the University of Calgary.
From the Quality Safety and Health Information database, we initially identified 1,232 patients who matched our inclusion criteria of being at a gestational age of 37 weeks or more or weighing 2,500 g or more. Figure 1 shows the process for selection of the final study sample of 1,193 paired maternal-infant charts. Infants 35 weeks of gestation or less were excluded from the analysis, but infants at 36 weeks or more AND weighing 2,500 g or more were included. The mean (standard deviation) maternal age was 32.1±4.8 years. Spontaneous onset of labor before cesarean delivery occurred in 225 of 1,193 women (18.9%), of whom, 142 reported symptomatic contractions, and 104 had spontaneous rupture of membranes.
Eighty-nine percent of the women had had a previous cesarean delivery. The remaining cesarean deliveries were performed for breech (6.5%), twins (1.9%), placenta previa (1.1%), primary elective (0.8%), and previous uterine surgery (0.4%), and the remainder comprised a combination of nonreassuring fetal testing before labor, active genital herpes, maternal diabetes, and no indication provided. Overall, the women were healthy, with few pregnancy-related medical problems. A third of the mothers were more than 35 years of age, and 13–15.9% were obese, correlating with 7.1–8.0% having diet-managed diabetes, with no difference between mothers whose infants had symptoms of respiratory distress and those who did not (Table 1). The prevalence of pregnancy-induced hypertension and maternal smoking was low compared with the general population of pregnant women in the Calgary Health Region.12
The mean (±standard deviation) gestational age of the infants at time of elective cesarean delivery was 271.4±6.7 days or 385/7 weeks. The mean birth weight was 3,397±480 g. Fifty-two percent were male infants. We had restricted the sample to a gestational age of 36 weeks or more, but when we calculated the gestational age from the expected date of delivery provided on the delivery record, we detected one patient who was at 35 weeks of gestation. This patient was not removed from the analysis. Forty-eight infants were delivered at 36 weeks, 23 of whom delivered after spontaneous onset of labor. Twenty-three (1.9%) infants were from twin sets, and the gestational age of these infants ranged from 254 to 268 days (362/7 to 382/7 weeks). Five of these infants were at a gestational age of less than 259 days (370/7 weeks). From the 23 twin infants, three were admitted to NICU.
Overall, 156 (13.1%) infants delivered by elective cesarean were admitted to NICU. By comparison, the regional Quality Safety and Health Information data for the preceding year identified an admission rate to the NICU of 7.3% for all infants delivered vaginally with birth weight of 2,500 g or more.
Using the prespecified definition of respiratory distress, 126 infants were identified to have respiratory distress, although only 118 of these infants were admitted to NICU. Therefore, 9.9% of the infants delivered by elective cesarean were admitted to the NICU with respiratory distress. Table 2 shows the treatment for the infants admitted for respiratory distress. Most of the infants had symptoms of mild respiratory distress. We used a clinical diagnosis to identify respiratory distress because we expected that most of these infants would not be subjected to chest radiographs. The chest radiographs that were done were reviewed independently by two neonatologists (W.Y. and H.A.), and there was agreement in diagnoses of the 6 pneumothoraces and the three infants that received exogenous surfactant for hyaline membrane disease. The eight infants treated with continuous positive airway pressure and the additional infant intubated, but who did not receive surfactant, had a spectrum of retained fetal lung fluid to mild hyaline membrane disease. Other common treatment interventions for the infants admitted to the NICU included intravenous antibiotics for nine infants with suspected sepsis and gavage feeding for nine infants. Hypoglycemia was identified in eight infants and spontaneous pneumothorax in six infants. Two thirds of the infants admitted to the NICU with symptoms of respiratory distress had short stays, with a mean of 6.4 hours, but the remaining third had a mean length of stay of 1.9 days. Several infants with other diagnoses had lengths of stay beyond 7 days (Table 3).
The univariable analysis identified that both gender and gestational age were significantly associated with NICU admission and respiratory distress, but the presence of pre–cesarean delivery contractions or rupture of membranes was not. Multivariable logistic regression was then performed, including variables for fetal gender, gestational age at delivery, spontaneous rupture of membranes before cesarean delivery and the onset of symptomatic contractions before cesarean delivery. In this analysis only fetal gender and the length of gestation remained significantly associated with the risk of NICU admission or neonatal respiratory distress. Specifically, this analysis identified that a 1-day advancement in gestational age could reduce the risk for respiratory distress by 7% (odds ratio 0.93, 95% confidence interval 0.90–0.96) Table 4. There was also no significant interaction between gender and gestational age.
To further examine the relationship between neonatal respiratory distress and the length of gestation, a smoothed fit to the data was constructed. This identified a steady reduction in the risk of respiratory distress until 270 days of gestation or 384/7 weeks (Fig. 2). Given this finding, we dichotomized the variable for gestational age with this cut point for our final model, shown in Table 5. Additionally, we combined the presence of ruptured membranes or contractions into one variable. We felt this was justified because the management of both conditions in a woman booked for elective cesarean delivery was the same, that is, an immediate cesarean delivery.
In the final model, elective cesarean occurring beyond 270 days of gestation (384/7 weeks) significantly reduced the risk of NICU admission and the risk of respiratory distress, but again the presence of pre–cesarean delivery contractions or rupture of membranes did not further reduce this risk.
In our study, the risk for admission to NICU and development of neonatal respiratory distress were significantly associated with gestational age at time of elective cesarean delivery and male gender. In our population, if elective cesarean delivery were planned for beyond 270 days (384/7 weeks) of gestation, the risk of respiratory distress could be reduced by 50%, and NICU admission could be reduced by approximately 40% in these neonates. However, the impact of such a policy will be limited by the significant number of subjects who will go into labor before reaching this gestational age. Additionally, we anticipate that not all cases will be appropriate for delay of delivery until 384/7 weeks and that the risk of respiratory distress and neonatal admission will be one of the factors in considering the optimal time of delivery. Numerous studies have identified similar relationships between respiratory morbidity, need for NICU admission, and gestational age.8–11,13–15 The recommendation from these studies is that cesarean delivery at 39 weeks or later significantly reduces the risk of respiratory morbidity. These recommendations are stated in the American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 98, published in 1991.16
Previous studies have also suggested that labor before cesarean delivery reduces the risk of respiratory morbidity.6,8,10,11,13,14,16–18 This has led to the recommendation to consider delaying cesarean delivery until the onset of ruptured membranes or symptomatic contractions. However, our review of these studies found that many included women who had unplanned cesarean delivery after prolonged labor. Therefore, the applicability of this finding to women having an elective cesarean delivery shortly after rupturing membranes or developing contractions is dubious. Additionally, the studies that included only women with planned elective cesarean delivery were published before the routine use of ultrasonography for confirmation of gestational age. We think it is likely that in these studies the women who ruptured their membranes or presented with contractions were more likely to be truly at a term gestation than those who did not.
In our study we could not find any evidence of a protective effect of pre–cesarean delivery symptomatic contractions or ruptured membranes. One explanation for our findings is that the duration of labor or ruptured membranes was not long enough to elicit a fetal response to decrease lung fluid. This would explain the variance between our results and studies that evaluated the risk of respiratory distress after prolonged labor. It is, therefore, also difficult to reconcile our results with the theory that maturation of the fetal hypothalamic pituitary adrenal axis and production of fetal steroids is responsible for both labor and fetal lung fluid reduction. If that was the case, one would expect that early labor, as it is initiated by the fetus, is protective against neonatal respiratory distress. The older theory that the physical effects of labor on the fetus or a fetal response to established labor seems a better explanation for the difference between our results and those of other studies. It is also possible that not all of the patients with symptomatic contractions were in true labor. Given the usual clinical practice, very few of our subjects had documented progressive cervical dilatation before repeat caesarean delivery. This potential misclassification could have made it more difficult to detect a protective effect of labor. Although it would have been ideal to limit the diagnosis of labor to women with progressive cervical dilatation, this was not feasible in our retrospective study nor do we feel it would be practical in a prospective investigation.
Alternatively, it is also possible that our study sample size was too small to detect a reduction in the incidence of respiratory distress in the spontaneous labor and ruptured membrane groups. Although this is always an explanation for any negative finding, we think this is unlikely because our point estimates for the effect of pre–cesarean delivery ruptured membranes or labor were very close to the null values.
We also determined, as have others, that male sex is a risk factor for respiratory distress and NICU admission. Given this finding, we also investigated whether or not a later gestational age cut off for delivery could be considered for a male fetus. In our analysis, because the interaction term for gestational age and sex was not significant, we could not conclude that such a relationship exists. However, it is possible that our study was underpowered to detect a significant interaction between these factors.
Based on our findings, we do not think it is feasible or advisable to mount a clinical trial of a policy of awaiting labor or ruptured membranes before elective cesarean delivery. Our study clearly confirms previous work that elective cesarean delivery should be delayed, if possible, beyond 37 weeks of gestation. Specifically, our results indicate that the reduction in the risk of respiratory distress is completely manifested by 384/7 weeks of gestation.
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