Barrett JF, Hannah ME, Hutton EK, Willan AR, Allen AC, Armson BA, Gafni A, Joseph KS, Mason D, Ohlsson A, Ross S, Sanchez JJ, Asztalos EV; Twin Birth Study Collaborative Group. A randomized trial of planned cesarean or vaginal delivery for twin pregnancy. N Engl J Med 2013; 369:1295-305. PMID: 24088091
Mikael Norman MD, PhD
Professor, Department of Neonatal Medicine
Karolinska Institute & University Hospital
TYPE OF INVESTIGATION
Does planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy?
- Design: randomized controlled trial
- Allocation: Concealed – randomization centrally controlled with the use of a computerized randomization program stratified according to parity and gestational age
- Blinding: Data for infants with the primary outcome events were adjudicated, with masking of the assigned group and (if possible) the method of delivery, by an adjudication committee.
- Follow-up period: Mothers and infants followed until 28 days after delivery
- Setting: 106 participating centers in 25 countries (in North and South America, Australia and Europe). Participating centers were required to have qualified obstetricians experienced at vaginal twin delivery.
- Patients: Women were eligible if they had a twin pregnancy between 320 and 386 of gestation, the first twin was in the cephalic presentation, and both fetuses alive with estimated weights between 1500 g and 4000 g.Exclusion criteria: monoamniotic twins, fetal reduction at 13 or more weeks of gestation, lethal fetal anomaly, contraindication to labor or vaginal delivery (e.g., fetal compromise, second twin substantially larger than the first twin, fetal anomaly or condition that might cause mechanical problems at delivery, and previous vertical uterine incision or more than one previous low segment cesarean delivery). Detailed participant characteristics are available on-line:http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214939/suppl_file/nejmoa1214939_appendix.pdf
- Intervention: Delivery by means of either cesarean section or labor induction (for women in the planned vaginal-delivery group) between 37 weeks 5 days and 38 weeks 6 days of gestation.
- Primary outcome: a composite of fetal or neonatal mortality or serious neonatal morbidity.Neonatal mortality was assessed for the period from 0 to 27 days after birth. Serious neonatal morbidity was defined as one or more of the following: birth trauma (spinal cord injury, basal or depressed skull fracture, fracture of a long bone, injury to brachial plexus or phrenic or facial nerve); subdural or intracerebral hemorrhage; Apgar score of less than 4 at 5 minutes; coma, stupor, or decreased response to pain; seizures; need for assisted ventilation within 72 hours after birth; septicemia or meningitis; necrotizing enterocolitis; bronchopulmonary dysplasia; grade III or IV intraventricular hemorrhage; or cystic periventricular leukomalacia.
- Secondary outcome: a composite of maternal death or serious maternal morbidity before 28 days post partum.
- Analysis and Sample Size: a sample of 2800 pregnancies (5600 twins) was required in order to detect a reduction in the risk of the composite primary outcome of fetal or neonatal death or serious neonatal morbidity from 4% to 2% with a policy of planned cesarean delivery (80% power and a two-sided type I error of 0.05, allowing for a 10% rate of crossover between groups).
- Patient follow-up: Outcome data were available for 1392 women (2783 fetuses or infants) in the planned-cesarean-delivery group and for 1392 women (2782 fetuses or infants) in the planned-vaginal-delivery group.
Between December 13, 2003, and April 4, 2011, a total of 2804 pregnant women were enrolled, 1398 women were randomly assigned to planned cesarean section and 1406 to planned vaginal delivery.
There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P = 0.49).
There was no significant difference between the planned-cesarean-delivery and planned-vaginal delivery groups in the frequency of the maternal composite outcome (7.3% and 8.5%, respectively; P = 0.29).
There were no significant interactions for the primary outcome between treatment group and parity, gestational age at randomization, maternal age, presentation of the second twin (cephalic vs. noncephalic), chorionicity, or the national perinatal mortality in the mother’s country of residence. The second twin was more likely than the first twin to have the primary outcome (odds ratio, 1.90; 95% CI, 1.34 to 2.69, P<0.001), however, planned cesarean section did not reduce this risk.
The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. The most common causes for cesarean delivery in the planned-vaginal-delivery group were failed induction of labor, maternal complication and antepartum hemorrhage.
In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery.
In this unique international effort to find evidence for the optimal mode of delivery for twins, planned cesarean section did not reduce the risk for perinatal death or serious neonatal morbidity as compared to vaginal delivery. As pointed out by the authors, this finding may in part be explained by the high rate of cesarean section (>40) in the planned-vaginal-delivery group, with most of these deliveries occurring during labor. Nevertheless, the design, the size of the study, and high follow-up rate suggest that the findings are robust.
Why is this knowledge important to neonatologists? Mainly, because the neonatologist is an important participant in counseling of women (and their partners) having twins, as well as in discussions with the obstetricians responsible for the delivery. With expectations of being the expert advisor acting in “the best interest of the baby”, the professional role of the neonatologist is to provide and discuss the safest mode of delivery. In this context, the study by Barrett et al is central.
The twin birth study is also reassuring for those who try to challenge the ongoing increase in cesarean section rates, not only for twin births,1 but also in general.2 Today, cesarean section is the most common surgical procedure in women of reproductive ages and in many large countries and hospitals, cesarean section rates exceed 50% by far. Besides the Twin Birth Study and the Term Breech Trial,3 there is a very weak evidence-base for cesarean section outside the emergency situation. For example, there is no randomized controlled trial testing cesarean section for preterm birth, still cesarean section is often recommended for deliveries occurring before term. Given that half of the infants in the Twin Birth Study were born at 32-36 weeks of gestation, there seems to be little evidence for improved outcome after planned cesarean section in moderately preterm infants. On the contrary, the opposite may be the case as suggested by observational data.4,5
In this study, only short-term maternal and infant outcomes were compared. Epidemiological studies have reported associations between birth by cesarean section and later health problems, such as increased risk for chronic immune disorders.6 While the underlying pathways for these associations are still obscure,7 it seems important that further long-term follow-up of participants in the Twin Birth Study will take place.
- Arabin B, Kyvernitakis I, Liao A, Zugaib M. Trends in cesarean delivery for twin births in the United States: 1995-2008. Obstetrics and gynecology 2012;119:657-8; author reply 8-9.
- OECD Health Statistics 2013, http://dx.doi.org/10.1787/888932917636
- Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group. Lancet 2000;356:1375-83.
- Malloy MH. Impact of cesarean section on intermediate and late preterm births: United States, 2000-2003. Birth (Berkeley, Calif) 2009;36:26-33.
- Altman M, Vanpee M, Cnattingius S, Norman M. Risk factors for acute respiratory morbidity in moderately preterm infants. Paediatric and perinatal epidemiology 2013;27:172-81.
- Sevelsted A, Stokholm J, Bonnelykke K, Bisgaard H. Cesarean section and chronic immune disorders. Pediatrics 2015;135:e92-8.
- Almgren M, Schlinzig T, Gomez-Cabrero D, et al. Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health? American journal of obstetrics and gynecology 2014;211:502 e1-8