Births between 34 and Concern about higher morbidity in late preterm infants has led to numerous publications with largely the same conclusions: Late preterm infants are more prone to problems related to delayed transition and overall immaturity, and they should be treated differently from their more mature term counterparts.21,39,56,79,85 These observations have led to greater attention being paid to tracking short-term morbidity, health care costs, hospital stays, and issues such as rehospitalization. Nearly three out of four preterm births occur at late preterm gestational ages, and this number has shown a steady increase over the past couple of decades.54 Although the problem seems to be widespread, similar estimates from other nations are not readily available. Evidence is emerging that the increase in the late preterm birth rate is not limited to the United States alone, but is a worldwide phenomenon, although reported rates seem to be quite variable. The late preterm birth rate was 5.9% in Canada in 2006.90 In Denmark, moderately preterm births (32-36 weeks) constituted 5.4% of all singleton live births, and this rate increased by 22% from 1995 to 2005. A Brazilian study estimated the late preterm birth rate to be 10.8% in that country.76 Preterm infants have been aptly and clearly classified for many decades. The World Health Assembly in 1948 described preterm infants as those weighing less than 2500 g or being less than 37 weeks’ gestation. In 1950, the World Health Organization revised this definition, identifying all infants born before 37 completed weeks’ gestation (259th day), counting from the first day of the last menstrual period, as preterm infants.70 The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (ACOG) agree with this definition.2 To clarify and to place a greater emphasis on the fact that these near-term infants have a greater risk of morbidity and mortality than term infants, an expert panel at a workshop convened by the National Institute of Child Health and Human Development of the National Institutes of Health in July 2005 recommended that births between 34 completed weeks (34 weeks or day 239) and less than 37 completed weeks ( In the United States, there were 3,953,593 live births in 2011, of which 11.7%, or approximately 480,000, were preterm.32,54 Late preterm infants constituted 71% of all preterm births (Figure 42-2). Preterm births have increased by nearly 20% during 1990 to 2006, but the late preterm birth rate has shown a much bigger increase of 25% and early term births nearly 50% during 1990 to 2006.54 Looking at only singleton births (because multiple gestations are prone to preterm birth), preterm births less than 34 weeks have declined 4% since 1990, but late preterm births have increased by 10%. Despite advances in obstetric and neonatal medicine over the last two decades, late preterm infants are primarily responsible for the entire increase in the preterm birth rate. A trend toward earlier deliveries is also seen at what is traditionally referred to as term gestation (≥37 weeks’ gestation). Singleton births at 40 weeks and greater have declined by 35% since 1990, and births at 37 to 39 weeks have increased by 30% over the same time period. According to birth certificate data for singleton births, there has been a gradual shift in the overall gestational length to 39 weeks from 40 weeks (Figure 42-3). The cause of this increase has been attributed in part to a rise in inductions, an increase in cesarean section rates, and a decrease in vaginal birth after cesarean (VBAC) rates.21,50 Recent data show that the preterm birth rate has finally started to decline; they were 8% lower than their 2006 peak, and the late preterm birth rate has declined 10%. The early term birth rate has also declined by 7% since 2006, and there has been a simultaneous rise in births at 39 weeks’ gestation by 11%.34,55 This decrease may be attributed to national efforts to decrease elective or non–medically indicated deliveries before 39 weeks’ gestation.13,65 This declining trend, although encouraging, still exceeds the rates in the 1990s and 1980s.54 Non-Hispanic black infants have nearly 1.5 times the late preterm birth rate than non-Hispanic white infants. The late preterm birth rate was 11% for singleton non-Hispanic black infants, 8.5% for Hispanic infants, and 7.8% for non-Hispanic white infants.54 Looking at only singleton late preterm births, rates increased by 35% for non-Hispanic whites and 10% for Hispanics between 1990 and 2005; for non-Hispanic blacks, the rate declined during 1990 to 2000, but has increased by 7% since 2000. Despite having the lowest rate of late preterm births, non-Hispanic white infants had the largest increase (35%) in late preterm births during 1990 to 2005.53 Because non-Hispanic whites are responsible for most US births, the overall increase in preterm birth rate in the United States can be explained largely by an increase in late preterm births among non-Hispanic white infants.17,53 Most recent data show that between 2005 to 2010, late preterm births have declined among all race categories, with the biggest percentage drop among the non-Hispanic whites and non-Hispanic black infants (Figure 42-4). Earlier studies indicated that late preterm infants have survival rates within 1% of term infants,36 but there is mounting evidence to show that late preterm infants have significantly higher mortality compared with term infants. Mortality rates in the 2009 period linked birth and death certificate data showing that late preterm infants have three times the mortality rate (7.13/1000 live births) compared with term infants (1.98/1000 live births) and even early term infants had higher mortality (3.09/1000 live births) compared with full-term infants.56 The etiology of prematurity is complex and multifactorial, and although known clinical entities such as pre-eclampsia and premature rupture of membranes (PROM) are significant contributors to preterm births, several other causes have been implicated in the increase in the late preterm birth rate (Box 42-1). Cesarean section rates have dramatically increased in the United States and worldwide, increasing from a low of 5% in 1970 to 31% in 2006.33 Among the many reasons cited for this increase are increased fetal surveillance and interventions, the increasing age of women giving birth, increasing number of multiple births resulting from fertility treatments, obesity, and heightened concerns of physicians and mothers about the risks of vaginal birth. In 2006, a national consensus conference coined a new term for cesarean deliveries for which no medical indication could be found and where maternal choice was the leading factor, cesarean delivery on maternal request.63 Although the exact number of such deliveries is hard to track, it is believed that 10% of cesarean sections may be performed at maternal request.72 Declercq and colleagues18 examined demographic and medical risk factors from 1991 to 2002, and found no association between changes in the maternal risk profile and the observed shifts in the primary cesarean section rates, implying that changes in maternal characteristics are not responsible for the increasing rate of cesarean sections. Davidoff and colleagues,17 looking at birth certificate data from 1992 to 2002, showed that all categories of live births have had an increase in late preterm (34-36 weeks’ gestation) and early term (37-39 weeks’ gestation) birth rates. Although spontaneous births and births from PROM declined during this period, births from medical interventions increased, with cesarean section accounting for most of the medical intervention group. Although elective cesarean sections are discouraged before 39 weeks’ gestation, a study by Tita and associates84 found that nearly 36% of elective repeat cesarean sections were performed before 39 weeks’ gestation. Among these elective cesarean births, infants born at 37 and 38 weeks had greater than 1.5 times the odds of death or complications, including respiratory compromise, hypoglycemia, sepsis, and admission to the NICU (Table 42-1).84 Induction rates have also increased with cesarean section rates, and there was a shift toward earlier gestations in both groups.17 In 2005, 22% of all singleton live births were induced. Of those, late preterm and term births had the largest increase in induction rates. Overall, the induction rates for late preterm births have increased 130% since 1990, and these rates have increased 175% for the early term group.53 Although medically indicated interventions have led to a decrease in the number of stillbirths, we do not know how much this has contributed to the increase in the preterm birth rate or whether the gains realized in preventing stillbirths are offset by increased NICU admissions and complications associated with prematurity (Figure 42-5). More recently, many states have implemented quality improvement programs to decrease elective deliveries before 39 weeks’ gestation. In one multistate collaborative undertaken over 12 months, elective scheduled early-term deliveries decreased from 27.8% in the first month to 4.8% in the 12th month; in addition, rates of elective scheduled singleton early-term inductions and cesarean deliveries decreased significantly.66 TABLE 42-1 Odds Ratios* for Adverse Neonatal Outcomes According to Completed Week of Gestation at Delivery *Odds ratio (95% confidence interval). †All outcomes are adjusted for maternal age (as a continuous variable), race or ethnic group, number of previous cesarean deliveries, marital status, payer, smoking status, and presence or absence of diet-controlled gestational diabetes mellitus. ‡Newborn sepsis included suspected infections (with clinical findings suggesting infection) and proven infections. Adapted from Tita AT, et al: Timing of elective repeat cesarean delivery at term and neonatal outcomes. N Engl J Med. 2009;360:111. Some evidence suggests that 2.5% to 18% of live births are delivered by cesarean section on maternal request.60,63 Other studies disagree,19,57 claiming that the increasing cesarean section rates stem from the changing practice standards of medical professionals and their willingness to perform cesarean sections because of the perceived safety and protection from malpractice litigation. Further prospective studies are required to quantify how much of the increase in late preterm births is owing to necessary medical interventions and how much can be attributed to cesarean section by physician or maternal request. Gestational age measurement is an inexact science; the methods currently used, such as the Naegele rule (which assesses gestational age from the first day of the last menstrual period) and ultrasound at 20 weeks’ gestation, are accurate only to ±1 to 2 weeks’ gestational age. Combined with the fact that developmental variability exists during fetal maturation, and conditions such as maternal obesity and PROM can cause an overestimation or underestimation of gestational age, the task of accurate gestational age prediction is even more challenging. In an attempt to reduce mortality among post-term gestations, ACOG in 1989 recommended induction of labor at 43 weeks.3 The Society of Obstetricians and Gynecologists of Canada later recommended induction at 41 weeks.15 The ACOG more recently issued guidelines that cesarean delivery or induction on maternal request should not be performed before 39 weeks’ gestation or without evidence of lung maturity.1 This gradual shift toward lower gestational age along with the inaccuracies of gestational age measurement might have led to the increasing proportions of late preterm births. Tocolysis and antenatal steroids are routinely recommended only for women at less than 34 weeks’ gestation because infants born at 34 weeks’ gestation and beyond are believed to have mortality rates similar to that of term infants.21 More recent studies have shown, however, that infants born at 34 weeks’ gestation are at 50% increased risk for requiring intensive care,22,25,38,59 and late preterm infants have increased morbidity, including long-term morbidities such as behavioral and developmental delay.11 This idea of a magical cutoff at 34 weeks when the fetus becomes mature compared with just a few days prior needs to be revisited in light of new evidence. Use of intrapartum fetal monitoring and prenatal ultrasound has been increasing over the years, from a rate of 68% and 48%, respectively, in 1989 to 85% and 67% in 2003.21 Prenatal ultrasound can lead to an overestimation of gestational age in maternal conditions associated with fetal macrosomia, such as obesity and gestational diabetes, both of which have increased rapidly in the last decade. There is the possibility of earlier intervention (induction or elective cesarean section) when ultrasound estimates are used to guide the management plan.70 Although fetal surveillance is designed to reduce adverse neonatal outcome, when coupled with antenatal tests with poor positive predictive value (biophysical profile, non-stress test), it may inadvertently increase medical interventions, with a resultant increase in late preterm and early term birth rates.21 More women are now choosing to have children at a later age; it is well known that preterm birth is more prevalent among women with advanced maternal age. Women older than 35 years old also have nearly twice the rate of cesarean section compared with women 20 to 24 years old. Increasing numbers of women are also seeking assisted reproductive technologies (ART); 38,910 women delivered infants through ART in 2005 (two times the 1996 rate), and more than 50% of these women were older than 35 years.9 Of infants born by ART, 32% were of multiple gestations, and these births are more likely to be preterm.10 From 1990 to 2005, the percentage of twins delivered preterm increased; late preterm births, which constituted 29% of these twin births in 1990, increased to 38% in 2005 (a 31% increase),53 and twin births from ART make up a significant proportion of this group. Studies have shown that singleton births from ART are also more likely to be preterm.5,10 It is surprising to some that late preterm infants, who are large and do not look anything like their tiny preterm counterparts, are at increased risk of medical complications related to prematurity. As their name implies, these infants are not term, however, and are prone to a host of clinical problems, including RDS, temperature instability, feeding difficulties, hypoglycemia, hyperbilirubinemia, apnea, late neonatal sepsis, prolonged hospital stay, and readmission.22–24,71,89 Thermoregulation in a newborn depends on the amount of brown adipose tissue, white adipose tissue, and body surface area (see Chapter 36).52 Nonshivering thermogenesis is controlled by the hypothalamic ventral medial nucleus through the sympathetic nervous system, which releases the neurotransmitter norepinephrine; this acts on the brown adipose tissue to liberate free fatty acids, which are eventually oxidized, producing heat. Late preterm infants have decreased stores of brown adipose tissue and the hormones responsible for brown fat metabolism such as prolactin, norepinephrine, triiodothyronine, and cortisol, which peak at term gestation. They are more likely to lose heat because of a decreased amount of white adipose tissue and less insulation. Also, their smaller size leads to an increased ratio of surface area to body weight, losing heat readily to the environment.22,52,68 Late preterm infants have poor coordination of sucking and swallowing because of neuronal immaturity, and have decreased oromotor tone, generating lower intraoral pressures during sucking.22,44,68,71 Poor caloric intake and dehydration result in exacerbation of physiologic jaundice, leading to readmission to the hospital for dehydration and jaundice. These infants also have decreased activity of hepatic uridine diphosphate glucuronyl transferase enzyme and increased enterohepatic circulation because of immature gastrointestinal function and motility. This decreased ability for hepatic uptake and conjugation puts late preterm infants at increased risk of elevated serum bilirubin levels, and jaundice is more prolonged, prevalent, and severe in these infants.7,24 One study showed that infants born at 36 weeks’ gestation have an eight times greater risk of developing a total serum bilirubin concentration greater than 20 mg/dL (>343 mmol/L) compared with infants born at 41 weeks or later.64 The fetus gets a steady supply of glucose primarily by maternal transfer through the placenta. Immediately after birth, this constant supply of glucose is cut off, and the infant has to produce glucose primarily by hepatic glycogenolysis and gluconeogenesis.31 The postnatal surge in catecholamines, glucagon, and corticosteroids plays an important role in maintaining euglycemic control. This increase in plasma concentrations of catecholamines causes a decline in circulating insulin concentrations and a subsequent surge in glucagon concentrations. Glucose-regulated insulin secretion by the pancreatic β cells is also immature, resulting in unregulated insulin production during hypoglycemia.27 Late preterm infants are challenged to maintain euglycemia control secondary to developmentally immature hepatic enzyme systems for gluconeogenesis and glycogenolysis, hormonal dysregulation with inadequate adipose tissue lipolysis, and decreased hepatic glycogen stores that are depleted quickly after birth.22,27,71
The Late Preterm Infant
weeks’ gestation (referred to herein as late preterm births) account for a significant proportion of preterm births in North America and elsewhere. These infants are larger than usual premature infants, and they are generally passed off as mature infants, but they often manifest signs of physiologic immaturity or delayed transition in the neonatal period. Several studies have documented the high incidence of neonatal complications leading to neonatal intensive care unit (NICU) admissions in these infants.75 They have a higher incidence of transient tachypnea of the newborn (TTN),89 respiratory distress syndrome (RDS),12,89 persistent pulmonary hypertension of the newborn (PPHN),75 respiratory failure, jaundice, temperature regulation problems, hypoglycemia, and feeding difficulties than term infants.20,23,26
Definition
weeks or day 259) of gestation be referred to as late preterm infants (Figure 42-1).71 Several factors led to this definition; 34 weeks is considered a maturational milestone in obstetric practice, after which surfactant is usually present in the lungs and is often used as a cutoff for giving antenatal steroids. Because there is no such thing as a normal preterm infant, and the name near-term might imply that these infants are as healthy as term infants, use of terms such as near-term was discontinued. More recently, data have shown that term infants born at 37 and 38 weeks’ gestation have higher morbidity and mortality than infants born at 39 weeks’ gestation.35,51,54,79 Engle and Kominiarek21 suggested identifying infants between 37 completed weeks’ gestation (37 weeks or day 260) and 38 completed weeks’ gestation (
weeks or day 274) as early term infants.
Epidemiology and Trends
Etiology
Medical Interventions and Iatrogenic Causes
Outcome†
37 Weeks
38 Weeks
39 Weeks
40 Weeks
Any adverse outcome or death
2.1 (1.7-2.5)
1.5 (1.3-1.7)
Reference
0.9 (0.7-1.1)
Adverse respiratory outcome
RDS
4.2 (2.7-6.6)
2.1 (1.5-2.9)
Reference
1.1 (0.6-2.0)
TTN
1.8 (1.2-2.5)
1.5 (1.2-1.9)
Reference
0.9 (0.6-1.3)
RDS or TTN
2.5 (1.9-3.3)
1.7 (1.4-2.1)
Reference
0.9 (0.6-1.2)
Admission to NICU
2.3 (1.9-3.0)
1.5 (1.3-1.7)
Reference
0.8 (0.6-1.0)
Newborn sepsis‡
2.9 (2.1-4.0)
1.7 (1.4-2.2)
Reference
1.0 (0.7-1.5)
Treated hypoglycemia
3.3 (1.9-5.7)
1.3 (0.8-2.0)
Reference
1.2 (0.6-2.4)
Hospitalization ≥5 days
2.7 (2.0-3.5)
1.8 (1.5-2.2)
Reference
1.0 (0.8-1.4)
Gestational Age Assessment and Obstetric Practice Guidelines
Advanced Maternal Age, Assisted Reproductive Technologies, and Multiple Births
Pathophysiology
Thermoregulation
Feeding
Glucose Homeostasis
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weeks’ gestation.
