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Reprints: Margreet J. Teune, MD, MSc, Department of Obstetrics and Gynecology, Academic Medical Center, PO Box 22700, 1105 DE Amsterdam, The Netherlands
Late-preterm infants (34 weeks 0/7 days-36 weeks 6/7 days' gestation) represent the largest proportion of singleton preterm births. A systematic review was performed to access the short- and/or long-term morbidity of late-preterm infants.
Study Design
An electronic search was conducted for cohort studies published from January 2000 through July 2010.
Results
We identified 22 studies studying 29,375,675 infants. Compared with infants born at term, infants born late preterm were more likely to suffer poorer short-term outcomes such as respiratory distress syndrome (relative risk [RR], 17.3), intraventricular hemorrhage (RR, 4.9), and death <28 days (RR, 5.9). Beyond the neonatal period, late-preterm infants were more likely to die in the first year (RR, 3.7) and to suffer from cerebral palsy (RR, 3.1).
Conclusion
Although the absolute incidence of neonatal mortality and morbidity in infants born late preterm is low, its incidence is significantly increased as compared with infants born at term.
The incidence of preterm birth, defined as delivery before the end of the 37th week (259th day) of pregnancy from the first day of the last menstrual period, is increasing. In the United States, the preterm rate rose from 9.1% in 1981 to 12.3% in 2003.
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.
In certain regions in Brazil the prevalence of preterm birth was 15% according to the 2004 Pelotas birth cohort, roughly 3 times the prevalence found in the 1982 birth cohort in the same city.
Infants born between the gestational ages of 34 weeks and 0/7 days through 36 weeks and 6/7 days (239th-259th day) are called near term or late preterm.
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.
Late-preterm infants account for about 74% of all preterm births and about 8% of all births. They are recognized as the fastest-increasing and largest proportion of singleton preterm births.
Several recent studies of late-preterm infants have documented increased short-term medical risks during their birth hospitalizations and increased adverse long-term outcomes (medical, social, behavior, school performance) compared to full-term infants.
Nevertheless, short- and long-term outcomes of late-preterm infants are not as frequently described as the outcomes of extremely preterm newborns and infants born late preterm are usually not entered in long-term developmental follow-up programs.
Gestational age and birth weight in relation to school performance of 10-year-old children: a follow-up study of children born after 32 completed weeks.
The aim of the current study was to perform a systematic review of the literature for medical and developmental short- and long-term outcomes of late-preterm infants to describe morbidity associated with late-preterm birth.
Materials and Methods
Search strategy
We performed an electronic search in PubMed, MEDLINE, Embase, and Cochrane trials databases (inception from January 2000 through July 2010) for original (cohort) studies that reported on short-term and/or long-term outcomes of infants born late preterm. The search parameters we used were “34 weeks” or “35 weeks” or “36 weeks” and “late preterm” or “near term” and “complications” or “morbidity” or “outcome.” To be included, a study had to report on the short- and/or long-term outcomes of late-preterm infants (34-36 weeks 6/7 days) compared to full-term infants (≥37 weeks). Reference lists of known articles were checked to identify cited articles not captured by electronic searches. Review articles were also excluded but their reference lists were screened for relevant studies. Cohort studies reporting on <50 infants were excluded. There were no language restrictions.
Data extraction
The following data were extracted from included articles: author, year of publication, methodological characteristics of each study, sample size, and short- and/or long-term outcomes. Short-term outcomes included neonatal outcomes such as Apgar score, need for mechanical ventilation or intubation, nasal continuous positive airway pressure, use of nasal oxygen, use of surfactant, presence of transient tachypnea, respiratory distress syndrome, persistent pulmonary hypertension, apnea, pneumothorax, pneumonia, meningitis, sepsis, hypoglycemia, feeding problems, hypothermia, hyperbilirubinemia, jaundice requiring phototherapy, and neonatal death. Long-term outcomes incorporated complications such as neurological morbidity, school performance, growth, and social outcomes. All articles were scored independently by 2 reviewers; disagreement was resolved by consensus or by a third reviewer.
Statistical analysis
All extracted information was systematically recorded in a database, in which we classified methodological characteristics of each study and their outcomes. For each outcome, we calculated the absolute risk (AR) of neonatal outcome and relative risk (RR) with corresponding 95% confidence intervals (CIs). Heterogeneity was explored by Cochrane Q2 test and I2. I2 can be interpreted as the proportion of total variation observed between the trials attributable to differences between trials rather than sampling error (chance).
I2 >75% is considered as a heterogeneous metaanalysis. We used a random effects model for pooling RR. Review Manager 5.0 (The Cochrane Collaboration, 2008; www.cochrane.org) was used to calculate these pooled effect estimates (RR and 95% CI).
Results
The results of the search strategy are shown in Figure 1. The electronic search detected 314 articles of which 48 were selected for full reading after studying the abstract. From these 48 articles, 8 studies were excluded because there was no full-term comparison group included.
The contribution of mild and moderate preterm birth to infant mortality: Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.
Gestational age and birth weight in relation to school performance of 10-year-old children: a follow-up study of children born after 32 completed weeks.
Twenty studies were excluded for other reasons (eg, studies reporting on <50 infants, review articles, not possible to make 2×2 tables). From references in selected articles and identified reviews, another 8 articles were included. Thus, 22 articles were available for the final review. These 22 studies included in total 2,368,471 late-preterm infants and 27,007,204 term infants.
The results of these 22 studies were used to calculate pooled RR and 95% CI if possible. For some outcomes high values of I2 (>75%) were found when calculating pooled RR. Nevertheless, almost all studies reporting on a specific outcome showed the same direction of effect (RR, >1). Characteristics of the included studies are presented in Table 1.
Table 2 shows the short-term outcomes of late-preterm infants compared to term infants. Late-preterm infants were more likely to suffer poorer short-term outcomes. The incidence rate was higher for late-preterm infants in 26 of the 27 short-term outcomes; 23 of these outcomes were significant (Table 2). Late-preterm infants had higher rates for neonatal death (0-28 days) than term infants (RR, 5.9; 95% CI, 5.0–6.9) with an AR of 0.38% vs 0.07% (Figure 2) . They were more likely to need mechanical ventilation (RR, 4.9; 95% CI, 2.8–8.6; AR, 2.5% vs 1.2%) or to suffer from respiratory distress syndrome (RR, 17.3; 95% CI, 9.8–30.6; AR, 5.3% vs 0.39%). Furthermore, they suffered more often from necrotizing enterocolitis (OR, 7.5; 95% CI, 3.3–17.3; AR, 0.11% vs 0.007%) and intraventricular hemorrhage occurred more often in late-preterm infants (OR, 4.9; 95% CI, 2.1–11.7; AR, 0.41% vs 0.09%). Table 3 shows the short-term outcomes of late-preterm infants by week of gestation compared to term infants for those studies that included such data. The shorter the term of pregnancy, the higher the risk was for neonatal morbidity and mortality.
TABLE 2Short-term outcomes of infants born late preterm compared to full-term infants
Eleven studies reported on long-term outcomes of late-preterm infants. Infant death in the first year after delivery occurred 4 times more among children born late preterm (RR, 3.7; 95% CI, 2.9–4.6; AR, 0.83% vs 0.27%).
Four studies reported adverse neurological development in later life. Late-preterm infants (n = 40,416) were more likely to suffer from cerebral palsy than infants born at term (n = 981,154) (RR, 3.1; 95% CI, 2.3–4.2; AR 0.43% vs 0.14%) and late-preterm infants (n = 40,203) were more likely to develop mental retardation than infants born at term (n = 977,505) (RR, 1.5; 95% CI, 1.2–1.9; AR, 0.81% vs 0.49%).
One of these studies (32,126 late-preterm infants, 852,157 term infants) also reported an increased risk of developing schizophrenia (RR, 1.4; 95% CI, 1.1–1.8; AR, 0.19% vs 0.14%), but no increased risk of autism (RR, 0.72; 95% CI, 0.40–1.3; AR, 0.03% vs 0.05%) in late-preterm infants.
However, another study (53 late-preterm infants, 1245 term infants) comparing cognitive, achievement, socioemotional, and behavioral outcomes between late-preterm infants and term infants showed that late-preterm offspring have no real deficits as they mature.
A fourth study (60 late-preterm infants, 35 term infants) examined general cognition, attention/working memory, language, manual coordination/motor dexterity, and visuomotor and executive function in preschoolers born late preterm (34-36 weeks) who required neonatal intensive care unit admission compared to term-born participants. In this study late-preterm birth was associated with visuospatial, visuomotor, and executive function deficits, but not with attention/working memory, receptive or expressive language, nonverbal reasoning, or manual coordination/dexterity deficits.
Several studies reported school outcomes. One of these studies (7152 late-preterm infants, 152,661 term infants) compared prekindergarten and kindergarten outcomes among healthy late-preterm infants and healthy term infants at birth. This study suggested that healthy late-preterm infants compared with healthy term infants face a greater risk for developmental delay and school-related problems through the first 5 years of life (developmental delay/disability between 0-3 years: RR, 1.4; 95% CI, 1.3–1.6; not ready to start school at 4 years: RR, 1.2; 95% CI, 1.0–1.3; exceptional student education at 5 years: RR, 1.1; 95% CI, 1.1–1.2; retention in kindergarten at 5 years: RR, 1.3; 95% CI, 1.2–1.4; suspension in kindergarten 5 years: RR, 1.5; 95% CI, 1.2–1.8).
Another study (970 late-preterm infants, 13,671 term infants) showed that infants born in the United States at 34-36 weeks' gestation without significant neonatal complications have greater rates of learning difficulties compared with full-term classmates. Late-preterm infants had lower reading scores than full-term infants in kindergarten to first grade. Teacher evaluations of math skills from kindergarten to first grade and reading skills from kindergarten to fifth grade were worse for late-preterm infants. Special education participation was higher for late-preterm infants at early grades.
Finally, late-preterm infants (n = 29,631) had a lower likelihood of finishing high school than term infants (n = 601,364) (RR, 0.96; 95% CI, 0.95–0.97; AR, 72% vs 75%).
Late-preterm infants (n = 25,193) are also less likely to complete university than term infants (n = 675,340) (OR, 0.87; 95% CI, 0.84–0.89; AR, 32% vs 35%).
One study (371 late-preterm infants, 2914 term infants) assessed the effect of late-preterm birth on growth outcomes when infants were 12 and 24 months. This study showed that late-preterm children grew faster than children born at term, but were at increased risk of underweight and stunting in the first 2 years of life. Failure to thrive in the first 2 years may put them at increased risk of future occurrences of serious morbidity in late childhood and of chronic disease development in adult life.
A Norwegian cohort study (29,711 late-preterm infants, 799,134 term infants) showed that late-preterm infants had a slightly higher risk to receive social security benefits (RR, 1.15; 95% CI, 1.12–1.17).
Nevertheless, late-preterm infants were less frequently studied compared with extreme preterm infants until recent years. In this study we estimate the magnitude of medical and developmental morbidity due to late-preterm birth. We demonstrate that late-preterm infants have a higher chance for respiratory complications, infections, intraventricular hemorrhage, feeding problems, hypothermia, and hypoglycemia, and they have a higher risk of mortality in the first year of life. Furthermore, late-preterm infants are at increased risk for long-term morbidity such as cerebral palsy and mental retardation. They have also a higher risk for problems during their school career.
A strength of this review is that both short- and long-term outcomes due to late-preterm birth were assessed and we have attempted to quantify those risks based on a large sample in multiple populations.
The study also has several limitations. It has been suggested that most of the excess neonatal morbidity in the late-preterm period is related to pregnancy complications (which include preeclampsia, intrauterine growth restrictions, placental abruption) leading to premature delivery rather than to prematurity by itself.
In this study, we included all infants born late preterm, both late-preterm infants born due to pregnancy complications and prematurity by itself. A subgroup analysis was not possible because of the limited number of eligible studies. Another limitation is that we have not made a selection in late-preterm infants based on, for instance, race, sex, maternal body mass index, mode of delivery, or administration of steroids. This might have resulted in high I2 for some outcomes. Thus, our results reflect the effect of all late-preterm births described in the consulted literature, whatever the cause of preterm birth and other patient or obstetric characteristics. Nevertheless, we think that the heterogeneity in risk profiles of adverse perinatal outcomes by gestational age at delivery provided strong impetus that future research should move away from associating the gestational at delivery, per se, to adverse outcomes, but should focus on the indication(s) for early delivery and the consequences of these indications on short- and long-term infant morbidity.
Our results suggest several areas for future research. More research is needed about the long-term outcomes, such as developmental delay and problems, school performance, and social outcomes due to late-preterm birth. Besides, information is needed about the specific fetal and maternal factors associated with late-preterm birth. We expect that the findings of this study will contribute toward determining the optimal obstetrical management as obstetricians and other clinicians weigh the risks and benefits to mother and child.
Conclusions
Late-preterm infants are recognized as the fastest-increasing and largest proportion of singleton preterm births. Although the absolute incidence of neonatal mortality and morbidity on the short and long term is low in infants born late preterm, its incidence is significantly increased as compared to term delivery. This information should be taken into account in the management of women who are at risk for preterm delivery near term.
References
Raju T.N.
Higgins R.D.
Stark A.R.
Leveno K.J.
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.
Gestational age and birth weight in relation to school performance of 10-year-old children: a follow-up study of children born after 32 completed weeks.
The contribution of mild and moderate preterm birth to infant mortality: Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.
This study was facilitated by Grant 80-82325-98-9010 from ZonMW , The Netherlands–Organization for Health Research and Development, The Hague, The Netherlands.
The authors report no conflict of interest.
Cite this article as: Teune MJ, Bakhuizen S, Gyamfi Bannerman C, et al. A systematic review of severe morbidity in infants born late preterm. Am J Obstet Gynecol 2011;205:374.e1-9.
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