Persistent pulmonary hypertension of the newborn, formerly referred to as persistent fetal circulation, is a life-threatening problem in neonates. In 1977, Maisels et al1 reported an association between elective repeat cesarean delivery and respiratory distress syndrome (RDS). In another report, investigators found an increased risk of general respiratory problems, including transient tachypnea of the newborn and RDS, in neonates delivered after elective repeat cesareans, compared with those delivered after a trial of labor.2 A case-controlled analysis of neonates who required extracorporeal membrane oxygenation specifically found an association of persistent pulmonary hypertension with elective cesarean delivery.3 Two other reports also linked persistent pulmonary hypertension to elective cesarean,4,5 but they had a limited number of deliveries. Cesarean delivery also was associated with persistent pulmonary hypertension of the newborn and with other antepartum variables.6 To confirm that association and to expand on it with more cases, we retrospectively analyzed our perinatal database of 29,669 consecutive deliveries with regard to a possible association between delivery mode and incidence of persistent pulmonary hypertension of the newborn, transient tachypnea of the newborn, and RDS.
Materials and Methods
We did a computerized retrospective review of 29,669 consecutive women who delivered at Illinois Masonic Medical Center between January 1, 1992 and December 31, 1999. Deliveries were grouped by delivery route and whether labor had occurred (all cesareans, elective cesareans, and all vaginal deliveries). Our perinatal database consists of information entered in a custom computer program each day by a chart abstractor, based on what providers write on the Hollister Labor and Delivery Summary Form for each delivery. The database was searched specifically for all cases of persistent pulmonary hypertension, transient tachypnea, and RDS, and the chart for each selected case was reviewed. Diagnoses of persistent pulmonary hypertension by our neonatologists were based on presence of right-to-left shunting at the the ductus arteriosus, foramen ovale, or both, documented by echocardiography or a significant pre- to postductal partial oxygen tension (pO2) gradient; the need for 100% oxygen to maintain arterial oxygenation between 60 and 70 mmHg; and no structural heart disease as determined by echocardiography. Diagnoses of transient tachypnea of the newborn were based on tachypnea that was relieved by minimal oxygen therapy (ie, < 40% oxygen) and chest X-ray showing prominent pulmonary vascular markings. Diagnoses of RDS were based on hypoxemia and acidosis, and chest X-ray findings of hyaline membrane disease (eg, a reticulogranular pattern). Only singleton live newborns were included. To limit the review to circumstances in which persistent pulmonary hypertension was most likely (at or near term), cases were excluded for one or more confounding variables, including pre-term delivery (gestational age less than 35 weeks), congenital heart disease, congenital diaphragmatic hernia, or meconium aspiration syndrome. χ2 analysis was done for statistical comparisons between the combined cesarean group and the vaginal delivery group, and between the elective cesarean group and the vaginal delivery group, for incidences of persistent pulmonary hypertension of the newborn, transient tachypnea of the newborn, and RDS. P values, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated using Simple Interactive Statistical Analysis online (http://Home.Clara.net/SISA/index.htm).
Among 29,669 deliveries at our institution from 1992–1999, 25,318 met the inclusion criteria. Table 1 is a compilation of data and statistical analyses from that cohort. There were 4301 cesareans (17%), and of those 1889 were elective. Seven hundred thirty-five scheduled cesareans were for breech presentation, placenta previa, genital herpes, macrosomia, or multiple gestation; the rest of the elective cesareans (1154) were done because of prior cesareans. During that period, 34 neonates (1.3 per 1000 live births) had primary diagnoses of persistent pulmonary hypertension of the newborn. Analysis showed that among 4301 cesareans, 17 resulted in the delivery of neonates who were admitted to the neonatal intensive care unit (NICU) and subsequently discharged with primary diagnoses of persistent pulmonary hypertension of the newborn (4.0 per 1000 live births). Among 1889 elective cesareans, seven resulted in neonates admitted to the NICU with persistent pulmonary hypertension (3.7 per 1000 live births). Among 21,017 vaginal deliveries at term, 17 resulted in neonates with persistent pulmonary hypertension (0.8 per 1000 live births).
Six neonates with persistent pulmonary hypertension were transferred to other institutions for therapy. No follow-up was available for them, but it is likely that some of them have died; therefore, we are unable to report accurately the mortality rate of persistent pulmonary hypertension in our population.
The combined incidence of all three respiratory problems in neonates delivered by cesarean was 4.5% compared with 1.4% of vaginally delivered neonates. The difference between incidences of respiratory diagnoses in the elective cesarean group (4.2%) compared with those of the vaginally delivered neonates was similar.
The incidence of persistent pulmonary hypertension of the newborn was one in 270 among newborns delivered by elective cesarean, a rate almost fivefold higher than that for neonates delivered vaginally. It is apparent that risk of transient tachypnea or RDS is greater than that of persistent pulmonary hypertension, but the risk of persistent pulmonary hypertension has a remarkably greater mortality rate.6,7 The risk of persistent pulmonary hypertension (about one in 1000 deliveries)6 was less than the incidence most often quoted for uterine rupture during a trial of labor after cesarean, from .07% to 1.3%.8,9 The neonatal mortality rate for uterine rupture during labor after cesarean did not exceed that without uterine rupture (about nine in 1000 live births),10 and therefore should be considered somewhat less than that for persistent pulmonary hypertension. McMahon et al11 showed that perinatal mortality rates did not differ between those born by elective repeat cesarean and those born after trials of labor. In our series, most elective cesareans were performed because of previous cesareans. In those cases, there were no conditions that threatened the fetuses, such as fetal bradycardia or abruptia placentae; therefore, labor and vaginal delivery could have been considered. That contrasts with cesareans after labor in which potential for harm existed.
There has been much discussion of methods to prevent group B streptococcal neonatal sepsis, the incidence of which has been reported as one to two per 1000 deliveries,12 a rate similar to that reported for persistent pulmonary hypertension (one per 1000 deliveries). Current obstetric standards recommend intrapartum chemoprophylaxis, particularly for perinates at risk of group B streptococcal sepsis, so it appears that neonates delivered by cesarean are at risk of acquiring persistent pulmonary hypertension. Although recent studies have reported promising results of extracorporeal membrane oxygenation and inhaled nitric oxide for treating persistent pulmonary hypertension, prevention of elective cesarean might greatly reduce mortality rates for that condition.
Respiratory conditions that prompted admission to the NICU (ie, persistent pulmonary hypertension and transient tachypnea) were almost threefold greater in the elective cesarean group than among vaginally delivered neonates, despite their having no conditions that threatened fetuses. Our findings confirm the risk of NICU-related morbidity for elective cesarean delivery. A report by Rawling and Smith13 did not identify elective cesarean as a risk factor, but they had fewer deliveries. Incidence of RDS in the elective cesarean group was similar to that in the vaginally delivered group. Our study design could not differentiate between cesarean delivery itself as a risk factor for persistent pulmonary hypertension or transient tachypnea, or the absence of labor, or both.
A likely hypothesis for persistent pulmonary hypertension after cesarean is that there might be an advantage to labor and vaginal delivery for the pulmonary vascular bed of the neonate. That hypothesis is supported by the finding that the interval of physiologic transient pulmonary hypertension after delivery was prolonged in neonates delivered by cesarean.14 Those neonatal circulatory differences were also shown by echocardiography by Jacobstein et al.15 Sulyak and Csaba16 postulated that the low rate of endogenous prostaglandin production during elective cesarean might be responsible for the high pulmonary hypoperfusion leading to persistent pulmonary hypertension. The mechanism of that advantage provided by vaginal delivery is not known. The physical compression of the perinate in the birth canal might be an additional potential benefit.
The prevalence of cesarean deliveries has remained stable during the past decade.17 There is a general belief in the obstetric community that cesareans result in improved perinatal outcomes. Few if any neonatal risks have been associated with cesarean delivery. Informed consent for cesareans focuses on maternal consequences. We confirmed and quantified the association of cesarean and neonatal risk of persistent pulmonary hypertension, and we expanded the risk to include cesarean after labor, which should be considered with any cesarean in which labor could otherwise occur safely. It is equally important to discuss such neonatal risk when offering a woman delivery options, in view of obstetricians' medicolegal obligations of informed consent.
Many cases of persistent pulmonary hypertension might be prevented with prompt and aggressive use of oxygen desaturations. Vigilant monitoring of neonates delivered by cesarean, especially elective cesareans, might prevent the high morbidity and mortality rates associated with persistent pulmonary hypertension.
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