Faculty Bibliography

Randomized controlled trials (RCT)s of surgery are fundamentally different from RCTs of medications because it is difficult to blind or mask a surgical procedure or perform "sham' operations. An additional challenge is the variation in skills and surgical proficiency of participating centers and surgeons. Addressing heterogeneity in surgical proficiency remains of paramount importance, especially when RCTs involve a new or complex procedure such as minimally invasive radical surgery. In the presence of such heterogeneity, it is very cumbersome to objectively evaluate and monitor surgical skills so that most trials simply report associations that are averaged across surgeons and hospitals/centers. Such reporting is non-transparent because the rates of complications and adverse outcomes are reported only as averages, and these averages may not apply to the individual participating surgeons or centers. These factors, coupled with the inherent non-generalizability of findings from such RCTs - due to the strict inclusion and exclusion criteria for enrollment - may lead to conclusions that no longer apply to real life for individual surgeons or centers. Case in point is a recently published non-inferiority RCT that reported that minimally invasive radical hysterectomy was associated with lower rates of disease-free survival (86% versus 96.5% at 4.5 years) and overall survival (93.8% versus 99% at 3 years) than open abdominal radical hysterectomy in patients with cervical cancer. However, RCTs involving two competing complex or new procedures may be affected by tremendous confounding due to variations in surgical proficiency and also non-standardization for other confounding factors such as patient selection categories (i.e. stage of cancer) and adjuvant post-operative therapies that may affect long-term survival. The purpose of this Viewpoint is not to provide an exhaustive review of the trial but to use it as an illustration to focus on two challenging areas that most RCTs of a new complex surgical procedure suffer from: un-adjusting or not correcting for surgical skill variability and non-transparent reporting of averaged results. We provide suggestions to overcome these deficiencies through robust methodological and statistical approaches.

BACKGROUND:Prior studies have reported an increased risk for preterm delivery following a term cesarean delivery. However, these studies did not adjust for high risk conditions related to the first cesarean delivery and are known to recur. OBJECTIVE:To determine if there is an association between term cesarean delivery in the first pregnancy and subsequent spontaneous or indicated preterm delivery. STUDY DESIGN/METHODS:This was a retrospective cohort study of women with the first two consecutive singleton deliveries (2007-2014) identified through a linked pregnancy database at a single institution. Women with a first pregnancy that resulted in cesarean delivery at term were compared to women whose first pregnancy resulted in vaginal delivery at term. Exclusion criteria were known to recur medical or obstetrical complications during the first pregnancy. A propensity score analysis was performed by matching women that underwent a cesarean delivery with those that underwent a vaginal delivery in the first pregnancy. The association between cesarean delivery in the first pregnancy and preterm delivery in the second pregnancy in this matched set was examined using conditional logistic regression. The primary outcome was overall preterm delivery <37 weeks in the second pregnancy. Secondary outcomes included type of preterm delivery (spontaneous versus indicated), late preterm delivery (34-36 6/7 weeks), early preterm delivery (< 34 weeks), and small for gestational age (SGA) birth. RESULTS:percentile for gestational age (3.6% versus 2.2%; aOR 1.26, 95% CI 0.52 - 3.06). CONCLUSION/CONCLUSIONS:After robust adjustment for confounders through a propensity score analysis related to the indication for the first cesarean delivery at term, cesarean delivery is not associated with an increase in preterm delivery, spontaneous or indicated, in the subsequent pregnancy.

Importance/UNASSIGNED:Whether the changing gestational age distribution in the United States since 2005 has affected perinatal mortality remains unknown. Objective/UNASSIGNED:To examine changes in gestational age distribution and gestational age-specific perinatal mortality. Design, Setting, and Participants/UNASSIGNED:This retrospective cohort study examined trends in US perinatal mortality by linking live birth and infant death data among more than 35 million singleton births from January 1, 2007, through December 31, 2015. Exposures/UNASSIGNED:Year of birth and changes in gestational age distribution. Main Outcomes and Measures/UNASSIGNED:Changes in the proportion of births at gestational ages 20 to 27, 28 to 31, 32 to 33, 34 to 36, 37 to 38, 39 to 40, 41, and 42 to 44 weeks; changes in perinatal mortality (stillbirth at ≥20 weeks, and neonatal deaths at <28 days) rates; and contribution of gestational age changes to perinatal mortality. Trends were estimated from log-linear regression models adjusted for confounders. Results/UNASSIGNED:Among the 34 236 577 singleton live births during the study period, the proportion of births at all gestational ages declined, except at 39 to 40 weeks, which increased (54.5% in 2007 to 60.2% in 2015). Overall perinatal mortality declined from 9.0 to 8.6 per 1000 births (P < .001). Stillbirths declined from 5.7 to 5.6 per 1000 births (P < .001), and neonatal mortality declined from 3.3 to 3.0 per 1000 births (P < .001). Although the proportion of births at gestational ages 34 to 36, 37 to 38, and 42 to 44 weeks declined, perinatal mortality rates at these gestational ages showed annual adjusted relative increases of 1.0% (95% CI, 0.6%-1.4%), 2.3% (95% CI, 1.9%-2.8%), and 4.2% (95% CI, 1.5%-7.0%), respectively. Neonatal mortality rates at gestational ages 34 to 36 and 37 to 38 weeks showed a relative adjusted annual increase of 0.9% (95% CI, 0.2%-1.6%) and 3.1% (95% CI, 2.1%-4.1%), respectively. Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality showed an annual relative adjusted decline of -1.3% (95% CI, -1.8% to -0.9%). The decline in neonatal mortality rate was largely attributable to changes in the gestational age distribution than to gestational age-specific mortality. Conclusions and Relevance/UNASSIGNED:Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality at this gestational age declined. This finding may be owing to pregnancies delivered at 39 to 40 weeks that previously would have been unnecessarily delivered earlier, leaving fetuses at higher risk for mortality at other gestational ages.

Importance/UNASSIGNED:Preterm and postterm deliveries have declined since 2005 in the United States, but the association between these changes and neonatal mortality remains unknown. Objective/UNASSIGNED:To estimate changes in the gestational age distribution among spontaneous and clinician-initiated deliveries between 2006 and 2013 and associated changes in neonatal mortality. Design, Setting, and Participants/UNASSIGNED:A retrospective cohort analysis was conducted of 22 million singleton live births without major malformations in the United States from 2006 to 2013. Data analysis was performed from August to October 2017. Main Outcomes and Measures/UNASSIGNED:Changes in gestational age distribution among spontaneous and clinician-initiated deliveries at extremely preterm (20-27 weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), term (39-40), late term (41 weeks), and postterm (42-44 weeks) gestations and changes in neonatal mortality rates at less than 28 days between 2006 and 2013. These changes were estimated from log-linear Poisson regression models with robust variance, adjusted for confounders. Results/UNASSIGNED:Among 22 million births, 12 493 531 (56.7%) were spontaneous and 9 557 815 (43.3%) were clinician-initiated deliveries. Among spontaneous deliveries, the proportion of births at 20 to 27, 28 to 31, 32 to 33, 34 to 36, and 37 to 38 weeks declined. Among clinician-initiated deliveries, the proportion of births at 34 to 36 and 37 to 38 weeks declined and the proportion at 39 to 40 weeks increased. Among spontaneous deliveries, overall neonatal mortality rates declined from 1.8 to 1.3 per 1000 live births, mainly at 20 to 27 weeks (adjusted annual decline, 1%; 95% CI, -2% to -1%) and 28 to 31 weeks (adjusted annual decline, 6%; 95% CI, -8% to -5%). Among clinician-initiated deliveries, overall mortality rates remained unchanged (2.1 to 2.2 per 1000 live births). However, mortality rates declined (0.6 to 0.5 per 1000 live births) at 39 to 40 weeks by 1% (95% CI, -3% to -0.4%) annually, adjusted for confounders. Conclusions and Relevance/UNASSIGNED:In the United States, there was a decline in spontaneous deliveries associated with an overall decline in neonatal mortality. Although clinician-initiated deliveries increased at 39 to 40 weeks, neonatal mortality at that gestation declined.