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Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South Florida, Tampa. He can be reached at DrLockwood@ubm.com.
Seven strategies to fight the rising tide.
Dr Lockwood, editor in chief, is Senior Vice President, USF Health, and Dean, Morsani College of Medicine, University of South Florida, Tampa. He can be reached at DrLockwood@advanstar.com.
The Centers for Disease Control and Prevention (CDC) preliminary report of 2015 birth outcomes contains some heartening news.1 The birth rate for teenagers aged 15 to 19 years continues to fall, dropping 8% in just 1 year, 46% since 2007 and 64% since its peak rate in 1991. And while the decrease wasn’t of the same magnitude, cesarean delivery rates also fell for the third year in a row to 32% from 32.2%. Moreover, the cesarean rate for low-risk women (ie, nulliparas with singleton fetuses in vertex presentations at term) dropped to 25.7% from 26.0%.
Unfortunately, after nearly a decade of declines, the US preterm birth (PTB) rate rose from 9.57% in 2014 to 9.62% in 2015. Interestingly, this increase was largely confined to late (34 to 36 weeks) PTBs, which increased from 6.82% to 6.87%. The increase was also fueled by a widening of the already serious racial disparity in PTBs. Rates increased among non-Hispanic black women from 13.23% to 13.39% while declining among non-Hispanic whites from 8.91% to 8.88%. While all these changes are small, they should be a wake-up call to reinvigorate our efforts to fully implement proven strategies to reduce PTBs.
The March of Dimes has been strongly advocating 7 strategies to reduce PTBs; my version of these interventions include:
Thus, the aging of our maternity wards, combined with the ongoing obesity epidemic, could certainly help account for a rise in indicated PTBs. The observed increase in racial disparity may either parallel these secular trends or be an independent contributor. Clearly we should avoid performing truly elective PTBs but a reduction in indicated PTBs will take a concerted societal effort to encourage women to reduce preconception weight and excess gestational weight gain through diet and exercise. It will also necessitate more aggressive blood pressure and glucose control among hypertensive and diabetic patients, respectively, both prior to and during pregnancy. Finally, it may also be time to for an honest discussion with younger women about the benefits of planning pregnancies between the ages of 25 and 35 years.
One cautionary note comes from the recent UK OPPTIMUM trial.19 This was a complex double-blind trial in which women were randomized to vaginal progesterone (200 mg per day) (n=618) versus placebo (n=1228) from 22–24 to 34 weeks if they had a prior PTB at ≤34 weeks, or a cervical length ≤25 mm, or a positive fetal fibronectin test combined with other clinical risk factors for PTB. The authors noted that progesterone did not affect the primary obstetric outcome of fetal death or birth <34 weeks (adjusted OR of 0.86, 95% CI: 0.61–1.22) or a composite neonatal outcome (OR 0.62; 95%CI: 0.38–1.03). However, this study mixed various risk categories and may have been underpowered for these outcomes. Also the presence of an elevated fetal fibronectin suggests that pro-parturition inflammatory processes may well have been under way by the time progesterone therapy was initiated. This is important because we have shown that both abruption (via thrombin) and infection (via interleukin-1Î²) are associated with significant down-regulation of decidual cell progesterone receptor levels20,21 and in the absence of its receptor even pharmacologic levels of progesterone will be ineffective.
Given these studies I would contend that progesterone therapy is best started early and, ideally prophylactically. Thus, I would recommend 17-OHP starting at 16 weeks in women with prior PTBs and high-dose vaginal progesterone for asymptomatic women with shortened cervix ≤20 mm, ideally started at 10 to 22 weeks, but certainly no later than 24 weeks and only if there is no evidence of infection or active abruption.
The recent national uptick in PTB rates may reflect the aging of our maternity population with its attendant accumulation of comorbidities triggering indicated PTBs. However, this increase should be a reminder that we must all do our best to optimize our patients’ lifestyle choices, BMI, fitness levels, and medical regimens prior to conception to reduce indicated PTBs. We should also fully employ the 7 practices described above that are known to reduce PTB rates. Our struggle against PTB is far from over and now is the time to redouble our efforts.
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Centers for Disease Control and Prevention. Trends in Smoking Before, During, and After Pregnancy-Pregnancy Risk Assessment Monitoring System, United States, 40 Sites, 2000–2010. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6206a1.htm. Accessed June 22, 2016.
Practice Committee of American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril. 2012;97(4):825-834.
Hamilton BE, Martin JA, Osterman MJ, Curtin SC, Matthews TJ. Births: Final Data for 2014. Natl Vital Stat Rep. 2015;64(12):1-64.
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Kresowik JD, Stegmann BJ, Sparks AE, Ryan GL, van Voorhis BJ. Five years of a mandatory single-embryo transfer (mSET) policy dramatically reduces twinning rate without lowering pregnancy rates. Fertil Steril. 2011;96(6):1367-1369.
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Conde-Agudelo A, Romero R, Nicolaides K, et al. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol. 2013;208(1):42.e1-42.e18.
Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012;206(5):376-386. Erratum in: Am J Obstet Gynecol. 2013;208(1):86.
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Grobman WA, Thom EA, Spong CY, et al. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012;207(5):390.e1-8.
Norman JE, Marlow N, Messow CM, et al. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016;387(10033):2106-2116.
Lockwood CJ, Kayisli UA, Stocco C, et al. Abruption-induced preterm delivery is associated with thrombin-mediated functional progesterone withdrawal in decidual cells. Am J Pathol. 2012;181(6):2138-2148.
Guzeloglu-Kayisli O, Kayisli UA, Semerci N, et al. Mechanisms of chorioamnionitis-associated preterm birth: interleukin-1Î² inhibits progesterone receptor expression in decidual cells. J Pathol. 2015;237(4):423-434.