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Spontaneous Late Preterm Births: What Can Be Done to Improve Outcomes?

Jay D. Iams, MD,* and Edward F. Donovan, MD
Despite the increase in indicated late preterm births, spontaneous preterm labor and preterm premature rupture of the fetal membranes are the most common antecedent diagnoses leading to births between 34-0/7 and 36-6/7 weeks of gestation. Regional and institutional variation in the rates of late spontaneous preterm birth suggests that there may be opportunities to reduce the number of these births. This article summarizes the factors contributing to late spontaneous preterm birth and offers suggestions to improve care for these mothers and infants. Semin Perinatol 35:309-313 2011 Elsevier Inc. All rights reserved. KEYWORDS late preterm, spontaneous preterm, preterm labor, preterm PROM, fetal maturity, quality improvement

n 2008, 12.3% of births in the United States were preterm (37 weeks gestation), and 71% of these (8.8%) were late preterm, occurring between 34-0/7 and 36-6/7 weeks gestation.1 Although these infants fare better than those born before 34 weeks gestation, they experience substantially increased morbidity and mortality compared with infants born after 37 weeks gestation, and in fact account for the overwhelming majority of admissions to neonatal intensive care. Antecedents of preterm birth are commonly categorized as either spontaneous or indicated, according to whether there were medical or obstetrical complications that led to the preterm birth. Spontaneous preterm births are dened as those that follow the spontaneous onset of labor, ruptured membranes, or related diagnoses, such as cervical insufciency, chorioamnionitis, or unexplained uterine bleeding or spotting. Approximately 70% of preterm births are spontaneous, but the relative percentage has decreased in recent years as indicated preterm births have increased.2 Between 1990 and 2006, the overall rate of preterm birth increased steadily from 7.9% to more than 12%. Almost all of this increase occurred in the late preterm period, and most of

*Ohio Perinatal Quality Collaborative, The Ohio State University Medical Center, Columbus, OH. Ohio Perinatal Quality Collaborative, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH. From and supported in part by The Ohio Perinatal Quality Collaborative: http://opqc.net/. Address reprint requests to Jay Iams, MD, 395 West 12th Avenue, Columbus, OH 43210-1267. E-mail: jay.iams@osumc.edu

that increase in singletons was explained by an increased rate of indicated preterm births. However, spontaneous late preterm births still account for more than 50% of late preterm deliveries and remain the leading cause of admissions to neonatal intensive care.3 Thus, improvements in care for conditions leading to spontaneous late preterm birth carry great potential to prevent or reduce perinatal morbidity and mortality. Most efforts to prevent and ameliorate the causes of spontaneous preterm birth have been directed at births before 32 weeks gestation, where rates of perinatal and infant mortality are the highest. Strategies to detect and arrest preterm labor and membrane rupture have been largely ineffective in preventing preterm birth but have been somewhat successful in prolonging pregnancy to allow administration of antenatal corticosteroids, antibiotics to reduce the risk of infection and prolong latency after preterm premature rupture of membranes (P-PROM), and to transfer the fetus in utero to an appropriate birth hospital. Before 34 weeks gestation, these benets are augmented by daily increases in fetal maturity. These efforts are considered successful if the pregnancy reaches 34 weeks, after which none of these strategies is deemed necessary. However, infants born between 34 and 37 weeks continue to experience increased morbidity and mortality and thus constitute a population at risk, risk that has until recently been considered minor and transient. Further prolongation of pregnancy between 34 and 37 weeks confers maturational benets that are less easily quantied. A closer look at their outcomes has revealed more short- and 309

0146-0005/11/$-see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semperi.2011.05.007

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Table 1 Diagnoses Antecedent to Late Preterm Birth at 3 Major Medical Centers n UTSW* 21,771 UT Houston 514 Ohio State 1700 Years 17 1 3 Indicated, PTL, P-PROM % % % 20 46 45 45 36 27 35 18 28

J.D. Iams and E.F. Donovan

Risks of Preterm Labor and P-PROM to the Mother and Fetus/Newborn

Preterm Premature Ruptured Membranes (P-PROM)
Expectant management of P-PROM is almost always accompanied by an increased risk of maternal infection that is made acceptable by the potential benet to the fetus and newborn of advanced maturity to be gained by waiting for spontaneous labor. However, after 34-0/7 weeks gestation, the literature consistently supports delivery as the safest option for mother and fetus in most cases because the risks of immaturity to the newborn, although common, are generally more easily managed in the nursery than sepsis. Unfortunately, the more subtle effects (learning disability, attention decit hyperactivity disorder, etc) have not been measured in this population. It would be nearly impossible to detect the benets of small prolongations of pregnancy on these outcomes. Despite these general conclusions, the optimal gestational age to minimize risks for mother, fetus, and newborn is clearly different for each patient. In a 2004 survey of maternal fetal medicine physicians, delivery was recommended for women with PPROM at 34-0/7 weeks gestation by 56% at 34 weeks, 26% at 35 weeks, 12% at 36 weeks, and 4% at 37 weeks gestation.9 Absent a better prediction model of the relative risks of fetal, neonatal and maternal infection versus global organ immaturity, prompt delivery at 34 weeks seems to be the safest choice for almost all women with P-PROM.10

Ohio State, the Ohio State University Medical Center, Columbus; PTL, preterm labor; UT Houston, University of Texas Health Science Center, Houston; UTSW, University of Texas Southwestern Medical School, Dallas. *McIntire and Leveno.6 Holland et al.7 Walton and Dyson.8

long-term adverse outcomes than are generally appreciated by the medical profession or the public.4 It is appropriate then to ask, where do these infants come from? Why are they born early? What are the antecedents of late spontaneous preterm birth, and isnt there something that can be done to improve their health at birth?

Prevalence and Demographics

Several studies of birth records have examined the sources of late preterm births with variable results. Reddy et al5 examined the records of 292,627 late preterm singleton births and found that 49% were associated with spontaneous labor. The proportion that followed P-PROM was not calculated separately but was 16%. Remarkably, no reason was recorded in 23% of late preterm births. Laughon et al3 evaluated records of 15,136 late preterm births from a population of more than 170,000. Late preterm births comprised 7.8% of all births and 65.7% of preterm births; 29.8% of late preterm births followed spontaneous labor; 32.3% preterm PROM; 31.8% had an obstetrical, maternal, or fetal condition leading to late preterm birth after induction of labor or cesarean delivery in the absence of labor, and 6.1% were unknown. Single-site studies that are smaller but more detailed also reveal variation in the relative percentages of late preterm births preceded by preterm labor, preterm PROM, or medical/obstetrical indications. Data from 3 tertiary medical centers summarized in Table 1 reveal substantial variation in the contribution of spontaneous versus indicated and preterm labor versus P-PROM to late preterm births.6-8 The variation may arise from population or coding differences but is equally likely related to local practice customs, creating opportunities for improvement. Late preterm births also vary regionally (Fig. 1). It is not clear why this is so, but states with the greatest rates of late preterm birth are also the states with the greatest percentage of African Americans, whose rates of spontaneous and indicated late preterm birth exceed that of other racial/ethnic groups.1

Figure 1 From March of Dimes Peristatsrates of late preterm birth by state. From http://www.marchofdimes.com/peristats/

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Spontaneous late preterm births
311 The considerations listed in Table 2 are dominated by and can be summarized as predictability of outcome. Expectant management of any complicated pregnancy carries the burden of continued surveillance for and measurement of adverse outcomes. Prenatal assessment and management of these risks is imperfect at all times but unfortunately varies with the clock and calendar. Although prematurity-related risks of delivery for the fetus decrease daily after 34 weeks gestation, today it is impossible to weigh those risks accurately against the risks of prolonging the pregnancy. The tolerance of risk by the American public and their health care providers is low. Thus, predictability of outcome is an important and unavoidable consideration in obstetrical management.

Preterm Labor
Risks for the mother with uncomplicated progressive preterm labor are not different from labor at full term. When preterm labor is complicated by maternal hemorrhage, trauma, or infection, progressive labor and delivery may introduce a transient increase in maternal risk as cardiac output increases. Cardiac work may rise further postpartum as the placental shunt is lost but the net effect of delivery is usually a decrease in maternal risk. Attempts to arrest preterm labor may add or introduce risk for the mother by prolonging the interval to delivery or by the side effects of the tocolytic drug chosen. The ratio of risks to benets of tocolysis for the fetus is difcult to assess after 34 weeks gestation, when in utero transfer and antenatal steroids are not necessarily helpful.

Relative Risks of Delivery Versus Expectant Management of Women at Risk of Spontaneous Late Preterm Birth
In most women with spontaneous preterm labor or P-PROM after 34-0/7 weeks of gestation, labor will progress with little opportunity to intervene except to administer antibiotics for group B streptococcal prophylaxis and to transfer the mother to an appropriate hospital. There are, however, several clinical scenarios in which physicians make decisions that affect the timing of delivery:

What Are the Opportunities to Improve Care for Women with Spontaneous Preterm Birth After 34 Weeks Gestation?
Despite clearly increased health risks for late preterm infants, the options for reducing the most common causespontaneous preterm parturitionseem limited. The marginal ability of drugs to arrest labor or prevent infection and the absence of evidence to support antenatal steroids at this gestational age leave caregivers with few traditional weapons. Several strategies have emerged.

Contractions persistent without cervical change; Cervical change, for example, 4-cm dilation without contractions; Suspected premature ruptured membranes without evidence of infection good history and low uid but no conrmation of rupture; and Vaginal spotting of uncertain origin. Clinical management of these situations is often not clear, there being no large series or trials to guide care. Before 34 weeks, patients with these problems are managed expectantly, but the calculus changes at 34-0/7 weeks. In each case, assessment of management options often favors allowing or even promoting delivery at that time (Table 2).

Late Preterm Steroids

There is currently little published evidence to support administration of antenatal corticosteroids after 34 weeks gestation, but neither is there reason to believe that steroids would not confer benet for late preterm infants destined to experience respiratory and other morbidities. In fact, a primary morbidity of concern in later preterm infants is lack of fetal lung maturity for which steroids seem to exert their primary benet. Stutcheld et al11 reported a 50% reduction in respiratory morbidity in infants born at 37 weeks gestation or longer by cesarean delivery. This and other studies prompted the ongoing Antenatal Late preterm Steroids (ALPS) Trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Network of Maternal Fetal Medicine Research Units.12 However successful this trial may be in demonstrating reduced respiratory morbidity in late preterm infants, it will not decrease and may even increase the number of infants born between 34-0/7 and 36-6/7 weeks if steroids provide coverage for choosing delivery over continuing a complicated pregnancy. It is important to note that steroids may provide no benet for other aspects of incomplete fetal maturation, such as hyperbilirubinemia, poor feeding, increased infection risk, and others. Late antenatal steroids will also not address the excess morbidity experienced by so-called early term infants born at 37 and 38 weeks compared with those born at 39 and 40 weeks.6,13 That problem will require a different approach.

Table 2 Risks and Advantages of Prolonging Pregnancy Complicated by Preterm Labor or Preterm PROM after 34-0/7 Weeks of Gestation Risks of Waiting Infection Abruption Cord prolapse Noncompliance Delivery en route back to hospital Malpresentation Stillbirth Advantages of Delivery Ability to monitor mother and fetus Rapid access to intervene Cesarean birth quickly available Enforced compliance Legal liability protection Predictability of outcome Falling fetal & neonatal mortality

PROM, premature rupture of membranes.

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ers, advocacy organizations, researchers, health systems, and government about the avoidable morbidity and even mortality associated with inappropriately scheduled births.25 It is reasonable to expect that extending this conversation to include births between 34 and 36 weeks might favorably inuence decisions about the relative merits and risks of indicated and spontaneous late preterm birth. Improved prospective documentation of the short- and long-term mortality and morbidity experienced by infants born after spontaneous late preterm birth by gestational week, growth percentile and demography could also improve ante- and post-natal care.

Culture Change
The care of women at risk of spontaneous late preterm birth illustrates the current obstetrical culture surrounding the 34 week benchmark: It has become a dating landmark, comparable with age 16 or even 21 years as an indicator of having arrived at an age at which certain behaviors are expected. Individually, our neonatal colleagues are sometimes complicit in this view, assuring obstetricians that the nursery can handle that and thus may be a safer place for an individual infant to reside. Collectively, however, we have burdened our neonatal colleagues with late preterm births that are now so routine that we may not even notify or consult them before birth. The result has been a marked increase in late preterm births, justied in part by the coincident decrease in fetal mortality, but accompanied by a cultural change in which gestational age has become conated with fetal maturity: 34 weeks is now viewed as usually mature and 37 weeks gestation, the lower boundary of term, has become mature. This culture change is illustrated by looking back to1972, when birth weight was the most common surrogate for fetal age and maturity. At that time, the different meanings of preterm and low birth weight were described as follows: Infants who are premature because of curtailed gestation (gestational age of 37 completed weeks) are designated preterm. . . . Infants who are premature by virtue of birth weight (2500 g or less at birth) are designated low birthweight infants.14 (Italics added.) The distinction made at that time was between age (preterm) and maturity (premature), a subtle difference that has been lost over time so that preterm has come to mean not fully mature, whereas term has come to mean mature. If these meanings are allowed to stand, then the denition of term should be revised so that it more accurately infers mature, ie, 39 rather than 37 weeks gestation, as suggested by Fleischman et al.15 Alternately, the word premature could be reintroduced to describe an infant of any gestational age who manifests immaturity of any organ system at birth.16 Regardless of how it is accomplished, a renewed appreciation of the maturity or immaturity of the fetus/infant, in addition to its age, could over time improve decision-making around the timing of delivery in complicated pregnancies.

Conclusions
The most common antecedent of late preterm births is spontaneous preterm parturition manifested as preterm labor, ruptured membranes, and/or progressive cervical effacement. Most of these births progress to delivery despite efforts to prevent or delay them. Improved outcomes for late preterm infants can be obtained by selecting the appropriate hospital to care for a premature infant and antibiotic prophylaxis according to current guidelines of care. Antenatal corticosteroid administration before late spontaneous preterm birth is currently being investigated. Increased attention to age-specic morbidity and mortality for premature infants of all gestational ages is needed. Improved awareness of the maturity of the fetus in addition to its gestational age may favorably affect decisions about perinatal care for these mothers and infants.

References
1. Martin JA, Hamilton BE, Sutton PD, et al: Births: Final Data for 2008. National Vital Statistics Reports; Vol 59 no 1. Hyattsville, MD, National Center for Health Statistics, 2010 2. Ananth CV, Joseph KS, Oyelese Y, et al: Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000. Obstet Gynecol 105:1084-1091, 2005 3. Laughon SK, Reddy UM, Sun L, et al: Precursors for late preterm birth in singleton gestations. Obstet Gynecol 116:1047-1055, 2010 4. Goldenberg RL, McClure EM, Bhattacharya A, et al: Womens perceptions regarding the safety of births at various gestational ages. Obstet Gynecol 114:1254-1258, 2009 5. Reddy UM, Ko CW, Raju TN, et al: Delivery indications at late-preterm gestations and infant mortality rates in the United States. Pediatrics 124:234-240, 2009 6. McIntire DD, Leveno KJ: Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol 111:3541, 2008 7. Holland MG, Refuerzo JS, Ramin SM, et al: Late preterm birth: How often is it avoidable? Am J Obstet Gynecol 201:e1-e4, 2009 8. Walton J, Dyson K, Iams J: Maternal indications and neonatal complications in late preterm birth [abstr 568]. Am J Obstet Gynecol 204: S227, 2011 9. Ramsey PS, Nuthalapaty FS, Lu G, et al: Contemporary management of preterm premature rupture of membranes (PPROM): A survey of maternal-fetal medicine providers. Am J Obstet Gynecol 191:1497-1502, 2004 10. Mercer BM: Preterm premature rupture of the membranes, in Berghella V, ed: Preterm Birth: Prevention and Management. New York, WileyBlackwell, 2010 11. Stutcheld P, Whitaker R, Russell I, et al: Antenatal betamethasone and incidence of neonatal respiratory distress after elective cesarean section: Pragmatic randomised trial. BMJ 331:662, 2005

The Importance of Births Near Term (36-0/7 to 38-6/7 Weeks Gestation)

Induction of labor or cesarean delivery in the absence of labor when there is no need for the birth to occur before 39-0/7 weeks, for example, a prior low transverse cesarean birth in a women who declines a trial of labor, or for nonmedical reasons, for example, convenience of the patient, should be scheduled only after 39-0/7 weeks gestation because maternal and infant morbidity and mortality are signicantly lower after 39-0/7 weeks than at 36-38 weeks of pregnancy.17-21 Inappropriate scheduling of such births before 39-0/7 weeks has been the subject of successful quality improvement efforts22-24 that include promotion of documentation of the specic reason(s) for scheduled birth. Some part of this success is due to not only to the projects but also to the coincident ongoing national conversation among providers, pay-

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Spontaneous late preterm births
12. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Network of Maternal Fetal Medicine Research Units. NICHD Network. Available at: http://www.bsc.gwu.edu/mfmu/. Accessed June 7, 2011 13. Clark SL, Miller DD, Belfort MA, et al: Neonatal and maternal outcomes associated with elective term delivery. Am J Obstet Gynecol 200:e1-e4, 2009 14. Chase HC, Byrnes ME: Trends in Prematurity: United States, Rockville, MD, Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration, NCHS, 1972, pp 1950-1967. DHEW publication no. (HSM)72-1030. (Vital and health statistics; series 3, no. 15. from Blackmore CA, Rowley DL, Kiely JL. Birth Outcomes. Available at: http://www.cdc.gov/ Reproductivehealth/ProductsPubs/DatatoAction/. . ./birout2.pdf. Accessed June 7, 2011) 15. Fleischman AR, Oinuma M, Clark SL: Rethinking the denition of term pregnancy Obstet Gynecol 116:136-139, 2010 16. Iams JD, Donovan EF, Rose B, et al: What we have here is a failure to communicate: Obstacles to optimal care for preterm birth. Clin Perinatol, in press 17. ACOG Practice Bulletin 10, 1999, reafrmed in 2009 as Induction of labor. ACOG Practice Bulletin No. 107: Induction of labor. American College of Obstetricians and Gynecologists. Obstet Gynecol 114:386-397, 2009

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18. Tita AT, Landon MB, Spong CY, et al: Timing of elective repeat cesarean delivery at term and neonatal outcomes. N Engl J Med 360:111-120, 2009 19. Clark SL, Miller DD, Belfort MA, et al: Neonatal and maternal outcomes associated with elective term delivery. Am J Obstet Gynecol 200: 156.e1-156.e4, 2009 20. Zhang X, Kramer MS: Variations in mortality and morbidity by gestational age among infants born at term. J Pediatr 154:358-362, 2009 21. Cheng YW, Nicholson JM, Nakagawa S, et al: Perinatal outcomes in low-risk term pregnancies: Do they differ by week of gestation? Am J Obstet Gynecol 199:370.e-1-370.e7, 2008 22. Oshiro BT, Henry E, Wilson J, et al: Decreasing elective deliveries before 39 weeks of gestation in an integrated health care system. Obstet Gynecol 113:804-811, 2009 23. The Ohio Perinatal Quality Collaborative Writing Committee: A statewide initiative to reduce inappropriate scheduled births at 360/7-386/7 weeks gestation. Am J Obstet Gynecol 202:e1-e8, 2010 24. Clark SL, Frye DR, Meyers JA, et al: Reduction in elective delivery 39 weeks of gestation: Comparative effectiveness of 3 approaches to change and the impact on neonatal intensive care admission and stillbirth. Am J Obstet Gynecol 203:e1-e6, 2010 25. Donovan EF, Besl J, Paulson J, et al: Infant death among Ohio resident infants born at 32 to 41 weeks of gestation. Am J Obstet Gynecol 203:e1-e5, 2010