When gestational age, birth weight, and sex are combined (Fig. 1), it becomes evident that at each gestational age, a lower birth weight carries a higher mortality risk. This effect is most pronounced in the lower ranges of gestational age and birth weight. In addition, when infants of similar gestational age and weight are compared, mortality rates are higher for males than for females. For example, a male born at 24 weeks of gestation weighing 700 g has a predicted mortality rate of 51%, whereas a female of the same age and weight has a predicted mortality rate of 35% (14).
These data apply to liveborn infants. Many of the smallest infants do not survive labor, do not respond to resuscitation, or are so small that resuscitation in the delivery room is not attempted. Among those who survive resuscitation in the delivery room, most deaths occur within the first 3 days of life (15,16). It is significant that the small proportion of infants weighing less than 500 g who do survive resuscitative efforts in the delivery room usually are female, small‐for‐gestationalage newborns (4).
▸ How should patients and their families be counseled about the morbidity associated with extremely preterm or extremely LBW infants?
Two recent large, prospective studies addressing morbidity —one using gestational age and one using birth weight—provide useful data. A gestational‐age‐based population study of 811 extremely preterm newborns used data collected in 1995 and found that disabilities in mental and psychomotor development, neuromotor function, or sensory and communication function were present in about one half of the large cohort of survivors at 30 months of corrected age (16). Approximately one quarter met the criteria for severe disability (16). Male newborns had lower psychomotor scores and were significantly more likely to have cerebral palsy than female newborns. A similar disadvantage for male newborns has been reported by others (2,17).
The most recent NICHD Neonatal Research Network study, which used data based on the birth weights of infants delivered at 14 tertiary care centers, reported similar results. Of all infants weighing 501–750 g, 100% had growth failure, 50% had intraventricular hemorrhage, 25% had grades III‐IV intraventricular hemorrhage, and 78% had respiratory distress syndrome (RDS) (14). The major morbidities influencing later development in these children included chronic lung disease, severe brain injury (intraventricular hemorrhage and periventricular leukomalacia), necrotizing enterocolitis, nosocomial infections, and retinopathy of prematurity.
▸ What are the risk factors for cerebral palsy at the threshold of viability?
A study from the NICHD Neonatal Research Network provided the first multicenter, prospective outcome data regarding the neurodevelopmental, neurosensory, and functional outcome of 1,151 extremely LBW newborns evaluated from birth to 18–22 months corrected age (Table 3) (2). Importantly, the sample size was sufficient to overcome some of the limitations that hampered the clinical applicability of earlier longitudinal outcome studies. One quarter of the children had an abnormal neurologic examination, approximately one third had a Bayley II Mental Development Index score less than 70 or a Psychomotor Developmental Index score less than 70 (normal for both these indices is >80), and 10% had visual or hearing impairment. Significant risk factors associated with cerebral palsy were grades III‐IV intraventricular hemorrhage, periventricular leukomalacia (odds ratio [OR], 3.05), and necrotizing enterocolitis (OR, 2.01). Risk factors for abnormal neurologic examination or Mental Development Index or Psychomotor Developmental Index scores less than 70 included grades III‐IV intraventricular hemorrhage, periventricular leukomalacia, chronic lung disease, use of postnatal steroids, necrotizing enterocolitis, a mother with less than a high school education, and male sex of the fetus.
▸ How does the assessment of gestational age affect counseling?
Gestational age often is well established. However, if gestational age is uncertain, it is important that the clinician consider a wide range of prognoses and care options and counsel the patient about a range of possible outcomes. Even relatively small discrepancies of 1 or 2 weeks in gestational age or 100–200 g in birth weight may have major implications for survival and long‐term morbidity.
In some cases—for example, in patients with little or no prenatal care—the gestational age is not established, and the clinician must consider data from fetal ultrasound measurements obtained near the time of anticipated delivery. Such measurements generally are not used to determine estimated gestational age unless they are the only data available. Although no single method has been determined to be superior, most ultrasound fetal weight formulas that include measurements of the fetal head, abdomen, and femur will yield a weight estimate within 15% of the actual weight (for weights <1,500 g) and a gestational age estimate within 2 weeks of the actual gestational age (from 20 to 30 weeks) (18). If there is a discrepancy of 2 weeks or more between the age based on menstrual dating and the age based on ultrasound measurements, or the woman is uncertain about the date of her last menstrual period, the physician may decide to make management decisions based on the ultrasound measurements, especially if measurements indicate a gestational age older than previously thought. If the measurements suggest a younger fetus, the possibility that the fetus is growth restricted should always be considered.
Ultrasonography also may provide useful information regarding the presence or absence of fetal malformations that may alter the prognosis of the fetus. However, fetal measurement and anatomic evaluation can be difficult in cases of multiple gestation or reduced amniotic fluid volume. Evaluation of multiple gestation also can be problematic because the prognosis for one infant may differ from that of the other(s).
▸ Does the mode of delivery affect neonatal outcome?
Few studies have evaluated the influence of obstetric management on the outcome of infants at the threshold of viability. Retrospective, nonrandomized studies have consistently failed to document a benefit of cesarean delivery for the extremely preterm fetus (19–23). It has even been difficult to document improved outcome with cesarean delivery for the extremely preterm fetus in breech position (20,21,24).
No prospective randomized studies of antenatal transfer of the extremely LBW infant to a tertiary care center have been reported. Retrospective data are difficult to analyze because the rapidity of labor, the severity of antepartum complications and the stability of the mother, the distance to the nearest high‐risk nursery, and other factors all influence transfer decisions. However, data from retrospective studies have demonstrated a decreased mortality risk for very LBW infants delivered at hospitals with a level III neonatal intensive care unit compared with delivery at hospitals with level I or level II neonatal intensive care units (25,26). Therefore, based on limited data, maternal transport to a tertiary care center should be considered when possible.
▸ Is there a benefit to the use of antenatal corticosteroids for extremely preterm births?
Although antenatal corticosteroids decrease the incidence of RDS in newborns at 29–34 weeks of gestation, randomized controlled trials have not shown a benefit in newborns treated between 24 and 28 weeks of gestation (27). In the largest randomized trial conducted on patients with intact membranes at 24–28 weeks of gestation, there was no benefit in the overall incidence or severity of RDS, but there was a significant reduction in the incidence of grades III and IV intraventricular hemorrhage (P = 0.01) (28). Although the precise impact of corticosteroids on RDS in pregnancies between 22 and 25 weeks of gestation has not been fully determined, the National Institutes of Health consensus conference statements on antenatal corticosteroid use recommended that all pregnant women at risk of preterm delivery between 24 and 34 weeks of gestation be considered candidates for a single course of corticosteroids (27,29).
What are the current recommendations and ethical considerations regarding resuscitation and continued support of the extremely preterm fetus?
Ethical decisions regarding the extent of resuscitative efforts and the subsequent support of the neonate are complex (30–32). The decision to withhold or withdraw support should not be made entirely on the basis of gestational age or birth weight, but should be individualized based on the newborn's condition at birth, survival and morbidity data, and the parents' preferences.
Each member of the health care team should make every effort to maintain a consistent theme in their discussions with family members regarding the assessment, prognosis, and recommendations for care. However, parents should understand that decisions about neonatal management made before delivery may be altered depending on the condition of the neonate at birth, the postnatal gestational age assessment, and the newborn's response to resuscitative and stabilization measures. It also is important that parents understand that the outcome depends on many factors (such as infection), some of which may not be obvious before delivery or even at the time of resuscitation. Recommendations regarding the extent of continuing support depend on frequent reevaluations of the neonate's condition, trends, and prognosis. The course of an individual newborn may change with time.
There are circumstances in which the withdrawal of life support may be appropriate, recognizing that the views of the parents are of prime importance. Compassionate care should be provided to the infant, including careful handling, maintenance of a neutral thermal environment, and gentle monitoring of vital signs.
Because it is difficult to predict how an individual extremely preterm newborn will develop, proactive programs to assess and support the infant through early school years are desirable (4). When the extremely preterm newborn does not survive, support should be provided to the family by physicians, nurses, and other staff after the infant's death. Perinatal loss support groups, intermittent contact by telephone, and a later conference with the family to review the medical events surrounding the infant's death and to evaluate the grieving response of the parents often are helpful.
Summary of Recommendations
The following recommendations are based on good and consistent scientific evidence (Level A):
▸ In general, parents of anticipated extremely preterm fetuses can be counseled that the neonatal survival rate for newborns increases from 0% at 21 weeks of gestation to 75% at 25 weeks of gestation, and from 11% at 401–500 g birth weight to 75% at 701–800 g birth weight. In addition, females generally have a better prognosis than males.
▸ In general, parents of anticipated extremely preterm fetuses can be counseled that infants delivered before 24 weeks of gestation are less likely to survive, and those who do are not likely to survive intact. Disabilities in mental and psychomotor development, neuromotor function, or sensory and communication function are present in approximately one half of extremely preterm fetuses.
The following recommendations are based on limited or inconsistent scientific evidence (Level B):
▸ Based on data from retrospective studies, maternal transport to a tertiary care center before delivery should be considered when possible.
▸ The effects of aggressive resuscitation at birth on the outcome of the extremely preterm fetus also are unclear. Therefore, management decisions regarding the extremely preterm fetus must be individualized.
▸ The effect of antenatal steroid use in the extremely preterm fetus is unclear; however, it is recommended that all women at risk of preterm delivery between 24 and 34 weeks of gestation be considered candidates for a single course of corticosteroids.
▸ Prospectively collected outcome data for extremely preterm fetuses are available. Whenever possible, data specific to the age, weight, and sex of the individual extremely preterm fetus should be used to aid management decisions made by obstetricians and parents of fetuses at risk for preterm delivery before 26 completed weeks of gestation. This information may be developed by each institution and should indicate the population used in determining estimates of survivability.
The following recommendations are based primarily on consensus and expert opinion (Level C):
▸ When extremely preterm birth is anticipated, the estimated gestational age and weight should be carefully assessed, the prognosis for the fetus should be determined, and each member of the health care team should make every effort to maintain a consistent theme in their discussion with family members regarding the assessment, prognosis, and recommendations for care.
▸ Because it is difficult to predict how an individual extremely preterm newborn will develop, proactive programs to assess and support the infant through early school years are desirable. When the extremely preterm newborn does not survive, support should be provided to the family by physicians, nurses, and other staff after the infant's death.
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The MEDLINE database, the Cochrane Library, and ACOG's own internal resources and documents were used to conduct a literature search to locate relevant articles published between between January 1985 and January 2001. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified articles. When reliable research was not available, expert opinions from obstetrician‐gynecologists were used.
Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force:
I Evidence obtained from at least one properly designed randomized controlled trial.
II‐1 Evidence obtained from well‐designed controlled trials without randomization.
II‐2 Evidence obtained from well‐designed cohort or case‐control analytic studies, preferably from more than one center or research group.
II‐3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence.
III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:
Level A—Recommendations are based on good and consistent scientific evidence.
Level B—Recommendations are based on limited or inconsistent scientific evidence.
Level C—Recommendations are based primarily on consensus and expert opinion.© 2002 The American College of Obstetricians and Gynecologists