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Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e3181f73f97
Original Research

Precursors for Late Preterm Birth in Singleton Gestations

Laughon, S. Katherine MD, MS; Reddy, Uma M. MD, MPH; Sun, Liping MD, MS; Zhang, Jun PhD, MD

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From the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

For a list of participating institutions, see the Appendix online at http://links.lww.com/AOG/A201.

The data included in this article were obtained from the Consortium on Safe Labor, which was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through Contract No. HHSN267200603425C.

Presented as a poster at the Annual Meeting of the Society for Pediatric and Perinatal Epidemiologic Research, June 22–23, 2010, Seattle, Washington.

Corresponding author: Dr. S. Katherine Laughon, Epidemiology Branch, NICHD, National Institutes of Health, 6100 Executive Boulevard, Room 7B03, Rockville, MD 20852; e-mail: laughonsk@mail.nih.gov.

Financial Disclosure The authors did not report any potential conflicts of interest.

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Abstract

OBJECTIVE: To characterize precursors for late preterm birth in singletons and incidences of neonatal morbidities and perinatal mortality by gestational age and precursor.

METHODS: Using retrospective observational data, we compared 15,136 gestations born late preterm with 170,593 deliveries between 37 0/7 and 41 6/7 weeks. We defined the following categories of precursors for late preterm delivery: “spontaneous labor,” “premature rupture of the membranes (preterm PROM),” “indicated” delivery, and “unknown.” Incidences of neonatal morbidities were calculated according to category of precursor stratified by gestational age at delivery. Neonatal morbidities and mortality associated with potentially avoidable deliveries (eg, “soft” precursors or elective) were compared between late preterm births and neonates born at 37–40 weeks.

RESULTS: Late preterm birth comprised 7.8% of all births and 65.7% of preterm births. Percentages of precursors were 29.8% spontaneous labor, 32.3% preterm PROM, 31.8% “indicated” (obstetric, maternal, or fetal condition), and 6.1% unknown. Different precursors for delivery were associated with varying incidences of neonatal morbidity. One in 15 neonates delivered late preterm for “soft” or elective precursors, and neonatal morbidity and mortality were increased compared with delivery at or after 37 weeks for these same indications.

CONCLUSION: A significant number of late preterm births were potentially avoidable. Elective deliveries should be postponed until 39 weeks of gestation.

LEVEL OF EVIDENCE: II

The overall rate of preterm birth before 37 weeks of gestation for singletons increased from 9.7% in 1990 to 11.0% in 2005, which was entirely due to the increase in preterm births between 34 and 36 weeks of gestation, designated as “late preterm” by the 2005 Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health workshop.1,2 Goldenberg et al have defined the obstetric “precursors” for preterm birth to be spontaneous preterm labor with intact membranes, preterm premature rupture of membranes (PROM), and delivery for maternal or fetal indications, known as “medically indicated.”3 The reason for the increase in late preterm births among singletons is secondary to an increase in medically indicated deliveries, rather than spontaneous labor or preterm PROM.4 Previous research on late preterm neonates has focused on their physiologic immaturity with associated higher morbidities and mortality compared with neonates born at 37 weeks of gestation or later.2,5–8 Less is known about the medical indications for late preterm delivery with only individual institutions reporting indications for a small number of women.9 It is important to know which medical indications for delivery have been driving the national increase in late preterm birth, because neonatal outcomes likely differ depending on the underlying pathophysiology of the pregnancy complication. It has also been shown that the actual indication for delivery is a factor in neonatal mortality.10 Additionally, medical and obstetric indications for delivery are heterogeneous and the evidence to guide the timing of delivery in certain pregnancy conditions is limited. There likely are some indications that can be expectantly managed with delivery at 37 weeks or later to decrease the risk of neonatal morbidity and mortality without a significant increase in stillbirth.2,5–8

We sought to provide epidemiologic data from the Consortium on Safe Labor, which reflects current obstetric practice in the United States. First, we quantified the proportion of different precursors for late preterm birth, with indicated deliveries further characterized by the individual medical and obstetric complications. We also calculated the incidence of neonatal morbidities and mortality by gestational age for the different precursors of late preterm birth. Finally, we wanted to further explore the morbidities associated with the proportion of deliveries that were potentially preventable.

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MATERIALS AND METHODS

The Consortium on Safe Labor was a study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and has been described in detail elsewhere.11 In brief, this was a retrospective cohort study involving 228,668 deliveries from 12 clinical centers and 19 hospitals representing nine American College of Obstetricians and Gynecologists districts. Women gave birth between 2002 and 2008. Institutional Review Board approval was obtained by all participating institutions. Women could have more than one pregnancy in the cohort, so to avoid intra-person correlation we included only the first pregnancy for a total of 206,969 women. One site that did not include indications for induction was excluded. There were 16,910 deliveries between 34 0/7 and 36 6/7 weeks of gestation. Of the late preterm births, 15,136 were singletons and 1,774 were multiple gestations (1,712 twin, 61 triplet, one quadruplet). We compared the 15,136 singleton gestations born late preterm with 170,593 singleton deliveries between 37 0/7 and 41 6/7 weeks of gestation.

Demographic data, medical history, labor and delivery information as well as obstetric, postpartum, and neonatal outcomes were extracted from patient electronic medical records from each institution. Data from the neonatal intensive care unit (NICU) were collected and linked to the newborn record. Maternal and newborn discharge International Classification of Diseases, 9th Revision, Clinical Modification codes were also collected for each delivery. Data were transferred in electronic format from each site and were mapped to common categories for each predefined variable at the data coordinating center. Investigators at each site completed surveys on hospital and physician characteristics. Data inquiries, cleaning, and logic checking were performed. Validation studies were performed for four key outcome diagnoses and the electronic medical records were found to be a highly accurate representation of the medical charts (more than 95% for the majority of variables).11

We defined the following categories of precursors for late preterm delivery: “spontaneous labor,” “preterm PROM,” “indicated” delivery, and “unknown.” The admission reason and indication for induction or cesarean delivery were used to identify the precursors for delivery. We identified any other maternal, fetal, obstetric, or demographic variables associated with the outcome of the pregnancy. We classified the precursors for delivery using the following hierarchy: women who presented in spontaneous labor were included only in the “spontaneous preterm birth” category even if they had other pregnancy complications (eg, maternal diabetes), and women with premature rupture of the membranes and not in labor were included as “preterm PROM.” Thus, if a woman presented both with preterm PROM and in spontaneous labor she was counted only once in the “spontaneous labor” category. If a woman did not present in spontaneous labor or with preterm PROM, we then identified all potential maternal, fetal, or obstetric complications of pregnancy, and included these in the “indicated” category. A woman could have more than one pregnancy condition in the “indicated” category. If there was no other reason, then we identified those women who were admitted to labor and delivery for an unspecified “fetal” or “maternal” reason and not in spontaneous labor or preterm PROM. These two categories were the only ones in the “indicated” category that were exclusive, and are specified as “admission for fetal reason, not otherwise specified” or “admission for maternal reason, not otherwise specified.” The “unknown” category included elective inductions or cesarean deliveries as identified by the site with no other obstetric, fetal, or maternal conditions, and also if there was no reason for induction or cesarean delivery provided and there were no other obstetric, fetal, or maternal conditions of the pregnancy.

We calculated the incidence of neonatal outcomes according to category of precursor of late preterm delivery stratified by the gestational age at delivery. Finally, we identified precursors for preterm delivery that could have been managed to deliver until 37 weeks of gestation and then potentially up to 40 weeks of gestation according to available evidence and expert opinion, and recategorized these as “soft precursors.” Soft precursors included suspected macrosomia without maternal diabetes12; uncomplicated gestational13 and chronic hypertension14; and history of fetal, maternal, or obstetric complication in a previous pregnancy (eg, history of preeclampsia in a previous pregnancy). We also identified “elective” induction or cesarean delivery as indicated by the site, with no other fetal, maternal, or obstetric complication. For late preterm birth, the soft precursors category came from both the original “indicated” and “unknown” categories. We did not include spontaneous labor or preterm PROM because those were likely the indications for the preterm delivery (ie, soft indications without spontaneous or preterm PROM).

To examine how delaying delivery for women with a soft precursor would affect neonatal outcomes, we considered that a woman with a soft indication might be either delivered late preterm or expectantly managed until term. We compared neonatal morbidity and mortality between late preterm births for a soft indication and neonates born at 37–40 weeks of gestation with the same array of (soft) precursors. For pregnancies at 37 weeks of gestation or later, a woman with a soft precursor who was being expectantly managed could have gone into spontaneous labor or had rupture of membranes. Thus, we included all women at term with a soft precursor at that gestational week of delivery for comparison (ie, soft precursors with or without spontaneous or PROM). Stillbirths at term were also included in the comparison group.

We performed logistic regression to calculate the odds ratios for neonatal morbidities (oxygen use, transient tachypnea of the newborn, mechanical ventilation, respiratory distress syndrome, apnea, pneumonia or sepsis, and admission to the NICU) and perinatal mortality with delivery at 37, 38, 39, or 40 weeks of gestation compared with delivery at 34–36 weeks of gestation (the referent group) in women with a soft or elective precursor for delivery. We combined 34–36 weeks of gestation as the referent group because our goal was not to show the difference between neonatal outcomes at 34, 35, and 36 weeks of gestation, but rather to investigate whether neonatal outcomes improve with each advancing week of delivery beyond preterm. A backward elimination was performed and variables considered included maternal race, parity, body mass index (calculated as weight (kg)/[height (m)]2), type of insurance, and smoking. All variables were significant with a P<.05 and therefore were adjusted for in the final model. χ2, Cochran-Armitage test for trend, analysis of variance, and Kruskal-Wallis tests were also performed where appropriate. Statistical analysis was performed using SAS 9.1.

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RESULTS

The 15,136 deliveries between 34 0/7 and 36 6/7 weeks of gestation accounted for 7.8% of all births and 65.7% of preterm births among singleton gestations. The characteristics of the women, their newborns, and the delivery are presented in Table 1. Women who had a spontaneous preterm birth and preterm PROM had a higher percentage of maternal age younger than18 years old, body mass index less than 25.0, and single status than women with indicated or unknown precursors or women who delivered at term. The cesarean delivery rate was twice as high for women with an indicated or unknown reason for late preterm birth (56.1% and 53.4%, respectively) compared with spontaneous preterm birth (22.0%), preterm PROM (23.2%), or women who delivered at term (27.0%). Birth weight less than 2,500 g was most frequent in indicated births (42.3%), but also more frequent in deliveries resulting in preterm PROM (36.0%) compared with spontaneous preterm labor (28.5%). When stratified by gestational week at delivery, the mean birth weight was 69, 54, and 59 g higher at 34, 35, and 36 weeks of gestation, respectively, for spontaneous preterm labor compared with preterm PROM (P<.001). There was not a clear association for physician age and precursors for late preterm delivery.

Table 1
Table 1
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Table 1
Table 1
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The percentage of precursors for late preterm births was 29.8% for spontaneous labor and 32.3% for preterm PROM. Another 31.8% of the late preterm births had an obstetric, maternal, or fetal condition (“indicated”). There were 6.1% with an “unknown” precursor, of which 175 (19.1%) were elective and 740 (80.9%) had no obstetric, fetal, or maternal conditions. With increasing gestational age at delivery, the percentage of spontaneous labor and unknown precursors increased and the percentage of preterm PROM and indicated reasons decreased (Table 2). Hypertensive disease was the most frequent condition for indicated late preterm birth, constituting 47.7% of indicated deliveries and 15.2% of all late preterm births. A maternal condition was the second most frequent complication of indicated late preterm birth (31.5%), followed by a fetal condition (29.7%).

Table 2
Table 2
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Respiratory morbidity and neonatal sepsis, as well as admission to the NICU and median NICU length of stay all decreased with advancing gestational age, regardless of the reason for late preterm delivery (Table 3). There were very few cases of seizures and intracranial hemorrhage at these gestational ages, with no obvious gestational-age effect. Neonates that were delivered because of complications of preterm PROM had decreased severe respiratory morbidity, including decreased mechanical ventilation and respiratory distress syndrome, compared with neonates that were delivered for the other categories. Indicated deliveries had a higher incidence of newborn sepsis and neonatal death at 35 and 36 weeks compared with the other categories and a higher incidence of admission to the NICU at every gestational age compared with the other categories.

Table 3
Table 3
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From the original “indicated” category, there were 869 (18.0%) deliveries for soft precursors and from the “unknown” category there were 175 (19.1%) elective deliveries with no other maternal, fetal, or obstetric complication, and together these 1,044 soft or elective precursors made up 6.9%, or approximately 1 in 15, of all late preterm deliveries (Table 4). The adjusted risk of oxygen use, transient tachypnea of the newborn, mechanical ventilation, respiratory distress syndrome, pneumonia or newborn sepsis, and admission to the NICU all were significantly decreased for neonates with soft or elective precursors delivered at 37, 38, 39, and 40 weeks of gestation compared with late preterm.

Table 4
Table 4
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DISCUSSION

Our large-scale study provides detailed information on precursors for late preterm births and associated neonatal outcomes. Spontaneous preterm birth, including spontaneous labor and preterm premature rupture of membranes, accounted for approximately two thirds of all late preterm births, and another third had an indicated precursor. A small percentage had no identifiable precursor. Some of these determinations may be the result of underreporting of maternal or fetal conditions; however, given the large number of different variables collected and our conservative effort to exclude all possible conditions, a certain proportion of these deliveries with an unknown precursor were likely truly elective. When combining pregnancies with a “soft” precursor for delivery or elective as indicated by the site with no other pregnancy complications, at least 1 in 15 of all late preterm births potentially could have been expectantly managed until 39 weeks of gestation.

When obstetric or maternal complications of pregnancy occur, caregivers have to balance the risks and benefits of delivery with expectant management for the maternal, fetal, and neonatal health to determine the optimal time for delivery. Our findings suggest that if delivery for women with a soft or elective precursor is delayed until 39 weeks of gestation, then neonatal morbidities may be decreased. In addition, current obstetric practice is to perform an amniocentesis to document fetal lung maturity before elective deliveries at less than 39 weeks. We did not have these data available; however, it is important to note that morbidities other than respiratory were still significantly decreased with delivery at gestational ages beyond 37 weeks compared with late preterm in deliveries with elective or soft precursors. Expectant management of these soft precursors was not associated with an increased risk of stillbirth or neonatal mortality in this study, and in fact is likely to be associated with a decreased risk of neonatal mortality.

It is not surprising or new that respiratory morbidity and neonatal sepsis, as well as admission to the NICU and median NICU length of stay, all decreased with advancing gestational age.5–7 However, the incidence of neonatal morbidities varied depending on the precursor for late preterm delivery. The differences in neonatal outcomes by type of precursor suggest that the underlying pathology for precursors is an important determining factor in neonatal morbidity. The precursor may directly affect neonatal risks, such as infection being more common in preterm PROM compared with spontaneous labor, and indirectly affect neonatal risks by influencing labor patterns and delivery route. For example, the lower rate of cesarean delivery for preterm PROM compared with indicated or unknown precursors may explain the lowest incidence of respiratory morbidity with this precursor. It has also been suggested that the increased NICU admissions in preeclampsia at term can be attributed to a high induction of labor and subsequent high cesarean delivery rate.15 Prolonged inductions with an unfavorable cervix also could increase the risk of chorioamnionitis and neonatal infections.

Our study is limited because we extrapolated the precursors for medically indicated delivery from indications for induction and cesarean delivery, which were not always provided. Thus, we were conservative and supplemented the precursors with any other medical, obstetric, or fetal conditions, even though those may not have been the actual indication for delivery. In addition, we were unable to determine whether an indication was a soft indication in certain conditions, such as small for gestational age with reassuring antenatal testing (normal nonstress test, biophysical profile score, amniotic fluid, and Doppler). Therefore, the true incidence of soft or elective precursors was likely higher than we have reported. This is supported by a recent study at a single center where 8.8% of the late preterm births were delivered for a mild stable condition, and an additional 8.2% were elective.16 Neonatal death was also not completely captured in our dataset, because neonatal deaths after hospital discharge could not be collected. However, this is a rare occurrence. Finally, the gestational age at delivery was the best obstetric estimate as determined by the clinician and transferred by the site. The study did not collect information on the accuracy of dating. However, this study represents current obstetric practice in the United States, so our findings can be extrapolated to a population where best obstetric estimating for gestational age is practiced.

Our results regarding risk of neonatal morbidities for soft or elective precursors should be interpreted with caution, because we are applying cross-sectional data to a longitudinal outcome. In a prospective study, women with a soft precursor for delivery would be identified at late preterm and randomized to delivery compared with expectant management. We did not know the timing of diagnosis for hypertensive disease, and therefore excluded women between 34 and 36 weeks with a soft precursor who had preterm labor or rupture of membranes, and we also included women at term who may have developed gestational hypertension after 36 weeks of gestation. However, we performed a sensitivity analysis for the most common soft precursor, hypertensive disease, and assumed the “worst case scenario,” that all women who developed severe disease had developed gestational hypertension between 34 and 36 weeks and were expectantly managed. Although the incidence of neonatal morbidities was slightly higher in this group, the odds ratios from logistic regression were similar, thus supporting our findings that if delivery for women with a soft or elective precursor was delayed until term, then neonatal morbidities may be decreased. In the absence of a randomized controlled trial, these are the best data we have from an observational study, and our findings support previous demonstration of decreased neonatal morbidities with delivery at later gestational ages.5–7

Our large, nationally representative cohort study provides epidemiologic data on the precursors for late preterm birth in current obstetric practice in the United States that can be used to target future prevention strategies for preterm delivery. Different reasons for delivery in the late preterm period were associated with differing rates of neonatal morbidity, which affects counseling regarding the risks and benefits of late preterm delivery. There were a significant number of women with a soft or elective precursor for delivery, and both neonatal morbidity and perinatal mortality may be decreased in those neonates delivered at or beyond 37 weeks of gestation compared with late preterm. We conclude that elective deliveries should be postponed until 39 weeks of gestation. More prospective data are needed and guidelines should be developed to help providers and women decide which soft precursors can be managed expectantly.

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REFERENCES

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2.Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics 2006;118:1207–14.

3.Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84.

4.Joseph KS, Demissie K, Kramer MS. Obstetric intervention, stillbirth, and preterm birth. Semin Perinatol 2002;26:250–9.

5.Rubaltelli FF, Dani C, Reali MF, Bertini G, Wiechmann L, Tangucci M, et al. Acute neonatal respiratory distress in Italy: a one-year prospective study. Italian Group of Neonatal Pneumology. Acta Paediatr 1998;87:1261–8.

6.Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics 2004;114:372–6.

7.Escobar GJ, Clark RH, Greene JD. Short-term outcomes of infants born at 35 and 36 weeks gestation: we need to ask more questions. Semin Perinatol 2006;30:28–33.

8.Tomashek KM, Shapiro-Mendoza CK, Davidoff MJ, Petrini JR. Differences in mortality between late-preterm and term singleton infants in the United States, 1995-2002. J Pediatr 2007;151:450–6, 456.e1.

9.Lubow JM, How HY, Habli M, Maxwell R, Sibai BM. Indications for delivery and short-term neonatal outcomes in late preterm as compared with term births. Am J Obstet Gynecol 2009;200:e30–3.

10.Reddy UM, Ko CW, Raju TN, Willinger M. Delivery indications at late-preterm gestations and infant mortality rates in the United States. Pediatrics 2009;124:234–40.

11.Zhang J, Troendle J, Reddy UM, Laughon SK, Branch DW, Burkman R, et al. Contemporary cesarean delivery practice in the United States. Am J Obstet Gynecol 2010 Aug 11 [Epub ahead of print].

12.Irion O, Boulvain M. Induction of labour for suspected fetal macrosomia. The Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000938. DOI: 10.1002/14651858.CD000938.

13.Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 2003;102:181–92.

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