PEDIATRICS Vol. 123 No. 1 January 2009, pp. 109-113 (doi:10.1542/peds.2007-3743)
ARTICLE |
Perinatal Outcomes Associated With Preterm Birth at 33 to 36 Weeks’ Gestation: A Population-Based Cohort Study
a Neonatal Service, Poole Hospital NHS Foundation Trust, Dorset, England
b Division of Child Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, England
c Division of Neonatology, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. The aim of our population-based study was to compare the mortality and morbidity of late-preterm infants to those born at term. Advancement in the care of extremely preterm infants has led to a shift of focus away from the more mature preterms, who are being managed as "near terms" and treated as "near normal." Some recent studies have suggested an increased risk of mortality and morbidity in this group compared with infants born at term. However, there are few population-based mortality and morbidity statistics for this cohort, particularly reflecting current practice.
METHODS. Using data from the British Columbia Perinatal Database Registry we analyzed all singleton births between 33 and 40 weeks’ gestation from April 1999 to March 2002 in the province of British Columbia, Canada. We divided this birth cohort into late preterm (33–36 weeks, n = 6381) and term (37–40 weeks, n = 88 867) groups. We compared mortality and morbidity data and associated maternal factors between the 2 groups.
RESULTS. Stillbirth rate and perinatal, neonatal, and infant mortality rates were significantly higher in the late-preterm group. Infants in this group needed resuscitation at birth more frequently than those in the term group. Late-preterm infants had a significantly higher incidence of respiratory morbidity and infection and had a significantly longer duration of hospital stay. Maternal factors that were more common in the late-preterm group included chorioamnionitis, hypertension, diabetes, thrombophilia, prelabor rupture of membranes, primigravida, and teenage pregnancy.
CONCLUSIONS. Our data support recent literature regarding neonatal mortality and morbidity in late-preterm infants and warrants a review of care for this group at the local, national, and global levels. Reorganization of services and increased resource allocation may be needed in most hospitals and community settings to achieve optimization of care for this group of infants.
Key Words: late preterm • near term • morbidity • outcomes
Abbreviations: RDS—respiratory distress syndrome • TTN—transient tachypnea of the newborn • RR—relative risk • CI—confidence interval
Progress in the frontiers of neonatology has continually pushed back the limit of viability and significantly improved the survival of extremely preterm infants.1–3 Increasing survival of extremely preterm infants coupled with their increased hospital stays4 has diverted the finite resources away from the infants born between 34 and 36 weeks of gestation (now termed the late-preterm group5,6).
These late-preterm infants have traditionally been labeled as "near-term" infants,5 treated as "near-normal" infants, grouped along with the well newborns,7 and discharged on the same schedule as term-born infants.8 The care of these infants has slowly moved away from neonatal units to transitional care units and to rooming in with parents in many cases.7–9
However, recent evidence5,6,10,11 suggests that this group of infants is not near normal, and managing them on the basis of such a perception may be inappropriate. Epidemiologic data from countries such as Canada, the United Kingdom, and the United States indicate an increase in the gestation-specific neonatal mortality rate between 6 and 8.5 times when compared with term infants.12–15 In Canada, late-preterm infants, although comprising only 4% of all live births, contribute 
10% of all early neonatal mortality.12 The recent increase in neonatal mortality rate in the United States has been attributed to the increasing proportion of moderately preterm infants.16 Late-preterm births are associated with increased morbidity when compared with the term-born population. Specifically, hypothermia,6 hypoglycemia,6 hyperbilirubinemia,10 respiratory distress,11 and difficulty initiating feeds17 have been found to be more common within this group compared with term neonates. Therefore, these infants deserve closer attention than their term counterparts. The number of larger preterm infants is much higher than extremely preterm infants,18 and good neonatal care of much shorter duration can potentially result in much improved outcomes. Unfortunately, in recent years, the trend has been in the opposite direction, with a tendency to discharge these infants earlier8,17 and to manage them like term infants.7,9
In response to recent literature from other parts of the world, we decided to study a cohort of late-preterm infants and to compare the neonatal characteristics and outcomes associated with birth at 33 to 36 weeks’ gestation (preterm group) with their term-born peers (term group).
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Data were obtained from the British Columbia (BC) Perinatal Database Registry and Reporting Tool of the BC Reproductive Care Program. This registry consists of data collected from facilities throughout the province and imported into the central BC Perinatal Database Registry. Data from the Canadian Institute for Health Information and matched files from the BC Vital Statistics Agency complement the data elements. Participation in the registry is voluntary and accounts for
99% of births in the province. The population used for this analysis included all singleton newborns identified in the database registry to be born at 33 to 40 completed weeks’ gestation between April 1, 1999, and March 31, 2002. For the analysis, newborns were categorized as late-preterm (born between 33–36 completed weeks’ gestation) or term (born between 37–40 weeks’ gestation). Gestational age was determined by early-gestation ultrasonogram in most cases. In cases where this was not available (minority of cases), it was the best estimate of the clinician involved in care.
The variables that were compared between the 2 groups included maternal risk variables including premature rupture of membranes, maternal diabetes, maternal hypertension, thrombophilia, and chorioamnionitis. We compared outcome variables including need for emergency cesarean section and resuscitation, 5-minute Apgar score below 7, respiratory morbidity, neonatal infection, and length of neonatal stay. Mortality data including death before 1 day, 7 days, 28 days, and 1 year were also compared.
For the purpose of this study, definitions of variables were based on preset definitions in the provincial database. Premature rupture of membranes was defined as rupture of membranes before the first stage of labor. The maternal diabetes variable included women who had preexisting diabetes mellitus, gestational diabetes, or an abnormal glucose-tolerance test result. The thrombophilia variable included women with circulating anticoagulants, and chorioamnionitis was defined as infection or suspected infection of the amniotic cavity as determined by clinical criteria by a physician. Primary emergency cesarean section was defined as cesarean section performed on an emergent basis on a mother who had not had a previous cesarean section. Neonatal outcome variables were defined as follows: need for resuscitation included need for bag and mask intermittent positive pressure ventilation, intermittent positive pressure ventilation through an endotracheal tube, cardiac compression, or drug administration in the neonatal stabilization period. Respiratory morbidity was defined as respiratory distress due to respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), or other conditions that caused clinical respiratory distress. Neonatal infection was a physician-defined variable that included culture-proven or suspected sepsis.
Statistical analysis was performed by using the 
2 test for significant differences in the proportions of perinatal characteristics and outcomes among the 2 gestation groups. A P value of <.05 was considered significant. We determined the relative risk (RR) ratios for the incidence of various adverse neonatal outcomes between the groups. The 95% confidence interval (CI) of the RR ratio was also calculated. The statistical package used was PEPI for Windows.19
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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During the study period the late-preterm group included 6381 infants, and the term group 88 867 infants. Demographic data for the study population are listed in Table 1.
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Mortality data are presented in Fig 1. The perinatal mortality rate was 8 times greater (95% CI: 6.2–10.4), the neonatal mortality rate was 5.5 times greater (95% CI: 3.4–8.9), and the infant mortality rate was 3.5 times greater (95% CI: 2.5–5.1) in the preterm group. Table 2 shows the age-specific RR of death between the 2 groups up to 1 year of life. The RR of death from day 1 up to 1 year of life gradually reduced from 11.4 to 3.5, showing that the maximum risk of death in the late-preterm group was in the first few days of life.
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There were significant differences among all the neonatal outcome variables compared between the 2 groups (Fig 2). Neonatal respiratory morbidity was 4.4 times greater in the preterm group (95% CI: 4.2–4.6), and neonatal infections were 5.2 times more common (95% CI: 4.6–5.9). The mean hospital stay was 142 hours in the preterm group compared with 57 hours in the term group.
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Comparison between maternal risk factors of the 2 groups is shown in Fig 3. The most important associations were the increased prevalence of chorioamnionitis (RR: 3.1 [95% CI: 2.6–3.7]), hypertension (RR: 2.5 [95% CI: 2.3–2.7]), and prelabor rupture of membranes (RR: 1.7 [95% CI: 1.6–1.7]) in the preterm group.
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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There has been steadily growing awareness of the clinical risks faced by late-preterm infants and the relative neglect of this cohort of infants in an era characterized by diversion of neonatal care resources4 toward securing survival of increasingly immature preterm infants. A growing body of research has demonstrated that mortality and morbidity for moderately preterm infants has been underestimated previously. Kramer et al,18 in their landmark study on the contribution of mildly and moderately preterm births on infant mortality, recognized that mildly (34–36 weeks) and moderately (32–33 weeks) preterm births contributed etiologic fractions of
7% to 9% and 4% to 6%, respectively, to all neonatal, postneonatal, and infant mortality rates. Wang et al,10 in a hospital-based study of late-preterm infants, found that temperature instability, respiratory distress, hypoglycemia, and jaundice occurred significantly more often in the preterm group. Many other data have come through in recent years regarding the morbidities seen in this cohort of infants,6,11,17,20,21 and these data were reviewed by Raju et al.5 It has to be emphasized that most of this literature was either hospital based or gave an indirect estimate of morbidity by disease-specific mortality rather than by population-based morbidity rates. The purpose of our study was to provide a population-based analysis of the mortality and morbidity rates of the late-preterm group.
Stillbirth Rates
In our study, stillbirth and perinatal mortality rates are 8 times higher in the preterm group. These results are consistent with the values derived from the Confidential Enquiry Into Stillbirths and Deaths in Infancy report,13 which gave an 11-fold higher stillbirth rate for the 32- to 36-week group compared with the term group.
Mortality Rates
With regard to neonatal mortality rates, the five-fold higher neonatal mortality rate in the preterm group in our study is comparable to the gestation-specific neonatal mortality rates from other data sources from Canada, the United States, and the United Kingdom.12–15 It is of interest that the RR of death decreases from 11-fold at day 1 to 3.5-fold when the deaths up to 1 year of age are taken into account (Table 2), which demonstrates that the need for extra care is particularly high in the first week of life. The values are similar to the RRs of 7.9, 3.6, and 3.0 calculated for early neonatal, late neonatal, and postneonatal mortality rates, respectively, for 34- to 36-week gestation births in Canada between 1992 and 1994.18 Excluding the neonatal period, risk of mortality between 28 days and 1 year is still 2 times higher in the preterm group, suggesting an unmet need for continued vigilance and follow-up (Table 2). This might be related to the fact that apparent life-threatening events and sudden unexplained deaths in infancy are much higher in late-preterm than term-born infants.22
Morbidity in Late-Preterm Infants
The occurrence of respiratory distress was nearly 4.5-fold higher in the preterm group than in the term group. The RR of the underlying diseases such as RDS, TTN, and other conditions causing respiratory distress could not be calculated from our data set. Wang et al, 10 in their retrospective comparison of infants born at 35 to 36 weeks’ gestation compared with 37 to 40 weeks, found a high incidence of respiratory distress in the former group with an odds ratio of 9.14. The frequency of respiratory distress seen in our study is similar to that quoted by Escobar et al11 from the United States and Rubaltelli et al23 from Italy.
Similarly, the incidence of suspected or proven infection is >5 times higher in the preterm group. This is similar to the odds of near-term infants undergoing evaluations for sepsis in the Wang et al study.10 Also, Tomashek et al17 analyzed data regarding readmission to hospital in late-preterm infants. Late-preterm infants had a higher incidence of hospital readmission when compared with term infants (3.5% vs 2%). Approximately one third of the readmissions were due to infections in both groups. It must be remembered that these studies offer only indirect measures of infection risk as opposed to our study, from which a population-based risk ratio for infection is available. A recent review highlighted the lack of data regarding infections in the late-preterm infant population.24
The increased frequency of primary emergency cesarean section in the preterm group suggests that in many cases, preterm labor does compromise the fetus. The mean length of hospital stay was greater in the preterm group, as it was in the Phibbs and Schmitt study,4 highlighting the fact that this group uses more neonatal care resources than the term group.
Maternal Factors
Presence of chorioamnionitis was 3 times greater in the preterm cohort. Thrombophilia and hypertension ranked as the next common factors (Fig 3). The incidence of maternal hypertension in the late-preterm group was 2.5 times more than the term group. Prelabor rupture of membranes was seen in 36.5% of preterm births (1.7 times more than in the term group), similar to the rate reported by others.25 The higher incidence of prelabor rupture of membranes and chorioamnionitis is compatible with a possible role of this complication in the etiology of preterm labor and may also contribute to the higher incidence of infection seen in the preterm cohort, as summarized by Hauth.26
Magnitude of the Problem
From our study and the literature, it is clear that the late-preterm group is significantly more vulnerable when compared with the term group. The magnitude of the risk has only recently been determined. Recognizing this, the recent workshop sponsored by the National Institute of Child Health and Human Development proposed that the term "late preterm" replace "near term" for infants born between 34 to 36 weeks’ gestational age, reflecting the increased risk of morbidity when compared with infants born at term.5
In 1996 in California, the average spending per case for newborns was $11 000 at 33 weeks’ gestation and $2600 at 36 completed weeks in contrast to an average of $1100 for term infants.27 Moreover, in the last 2 decades there has been a steady increase in the rate of late-preterm births. In the United States, the rate has increased by 15% from 1990 to 2002, whereas the rate of very preterm births has remained stable.16 Similarly, in Denmark, the rate of preterm births at 32 to 36 weeks increased by 22% from 1995 to 2004.28 It follows that in view of increased mortality and morbidity rates of late-preterm infants and their increasing numbers, appropriately increased resources should be directed to meet the needs for care of this at-risk group of infants.
Strengths
To our knowledge, ours is the first large population-based study to assess mortality and morbidity in a large cohort of infants born late preterm, with preset variable definitions. The data represent a large birth cohort over a period of 3 consecutive years. Our data support the recent drive to treat 33- to 36-week-gestation newborns as slightly more mature preterm infants rather than as slightly immature term infants.
Limitations
Limitations of our study include relative lack of stratification of certain variables based on underlying diseases. For example, the variable "respiratory morbidity" included diseases such as RDS, TTN, and other conditions causing respiratory distress in the newborn. However, stratification of this variable in a large population-based study would have been possible only at the expense of accuracy. The vital statistics data are incomplete because 1% of all births were not reported. However, we do not think that this limitation would significantly impact our findings.
It would have been very informative if we had analyzed the morbidities on the basis of week of gestation rather than grouping infants at 33 to 36 weeks’ gestation. Unfortunately, because of the nature of the database, it was not possible to analyze in this way. There need to be additional prospective studies that examine this. Future prospective studies can be designed to study the effect of maternal complications such as chorioamnionitis on neonatal outcome in the late-preterm group.
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CONCLUSIONS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The data presented in our study expand recent literature on the increased mortality and morbidity rates of the late-preterm group. These data, we hope, will be some of the many that will lead to review of care for the late-preterm group at the local, national, and global levels and help optimize care for this cohort of infants. Reorganization of services and increased resource allocation to provide better clinical support to this group may be needed in most settings. Our findings may also affect antenatal counseling regarding delivery at late-preterm gestation.
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ACKNOWLEDGMENTS |
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We thank Dr Michael Whitfield and Dr Ruth Milner for critical review of this manuscript.
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FOOTNOTES |
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Accepted Mar 27, 2008.
Address correspondence to Horacio Osiovich, MD, FRCPC, Children's and Women's Health Centre of British Columbia, Division of Neonatology, Room 1R47, 4480 Oak St, Vancouver, BC, Canada V6H 3V4. E-mail: hosiovich{at}cw.bc.ca
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Infants born after 33 weeks’ gestation have traditionally been labeled as "near term" and treated as "near normal." Some recent studies have suggested an increased risk of mortality and morbidity in this group of infants compared with term infants.
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| What This Study Adds To our knowledge, our study is the first large population-based study to assess mortality and morbidity in a large cohort of late-preterm infants. Our results support the recent drive to treat these infants as late-preterm infants rather than near-term infants.
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PEDIATRICS (ISSN 1098-4275). ©2009 by the American Academy of Pediatrics
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