Kathleen M. Berkowitz and Thomas J. Garite
Table Of Contents
Kathleen M. Berkowitz, MD
Thomas J. Garite, MD
DIAGNOSIS AND INCIDENCE
ETIOLOGY AND PATHOPHYSIOLOGY
The postdate pregnancy is one of the most common, yet challenging conditions currently facing obstetricians. The recognized increases in perinatal morbidity and mortality that occur in the postdate pregnancy mandate that the physician accurately diagnose and manage postdatism.1 The incidence of macrosomia, oligohydramnios, meconium aspiration, and cesarean section performed for fetal distress all are increased after 42 weeks of gestation.2,3,4 The postmaturity syndrome described by Clifford,5 characterized by placental dysfunction, meconium staining, and loss of subcutaneous fat reserves, complicates at least 20% of postdate pregnancies.6 Perinatal mortality rates, as determined by the National Birthday Trust data,7 begin to increase after 42 weeks and quintuple by 44 weeks of gestation. Despite all of the recognized risks attending the postdate pregnancy, its definition and diagnosis remain a topic of considerable discussion.
This chapter discusses what constitutes a postdate pregnancy, how to diagnose and manage its complications, what methods of fetal surveillance should be used, and how to decide the timing and route of delivery.
The accepted normal duration of pregnancy is 266 days after ovulation. The timing of an ovulatory event may be estimated as occurring 14 days after the first day of the last menstrual period if cycles occur at 28-day intervals. Ovulation occurring during longer or shorter cycles also can be estimated, providing the cycles are regular in length.
Postdate pregnancy, prolonged pregnancy, and postmaturity syndrome should not be used as interchangeable terms. A postdate pregnancy usually is defined as a pregnancy lasting more than 294 days, or 42 completed weeks after the first day of the last menstrual period. Whereas some physicians consider prolonged pregnancy and postdate pregnancy to be the same entity, others believe that the term prolonged pregnancy should be reserved for well-dated pregnancies known to exceed 42 weeks of gestation and that the term postdate should be used for the more global group of patients thought to be beyond 42 weeks. The postmaturity syndrome was described in detail by Clifford5 and advocates the use of a staging system to quantify increasingly severe clinical manifestations of placental dysfunction. Stage I is typified by a long, lean infant with wrinkled, peeling skin. Stage II includes the clinical findings of stage I and adds greenish meconium staining of amniotic fluid, fetal skin, and placental membranes. Stage III is characterized by a high incidence of fetal distress and yellow-brown meconium staining, indicative of the presence of meconium for several days. The incidence of the postmaturity syndrome increases with the length of pregnancy; at 42 weeks, about 20% of fetuses have stigmata of postmaturity.
|DIAGNOSIS AND INCIDENCE|
The incidence of postdatism decreases as the accuracy of the dating criteria used increases.8 The reported incidence of postdate pregnancy ranges from 3% to 17%.3,9,10 The advent of sensitive over-the-counter pregnancy test kits and the common use of early ultrasound for dating have improved the clinical estimation of conception in women who present early for prenatal care. Sonography is most useful when performed before the 20th week of gestation, with measurement of the crown-rump length in the first trimester as the most accurate parameter. Menstrual recall, early palpation of uterine size, and Doppler auscultation of fetal heart tones are less accurate but helpful methods used to determine the estimated date of delivery. However, many women are unable to accurately recall either the date of their last menstrual period or the regularity of their cycles.11 Amenorrhea caused by recent abortion, discontinuation of contraceptive pill use, or breast-feeding can obscure the timing of ovulation and conception. The presence of myomas may alter the estimation of uterine size. Other women may first present for care late in pregnancy or with a history of irregular menstrual cycles. Any of these factors decrease the accuracy with which the postdate pregnancy can be identified.
|ETIOLOGY AND PATHOPHYSIOLOGY|
Maternal age, parity, ethnicity, and history of prior pregnancy loss do not seem to be related to the incidence of prolonged pregnancy.8,12,13 Maternal history of a previous prolonged pregnancy,8 low socioeconomic status,13 maternal weight gain,2 and a history of first-trimester bleeding10 are associated with a higher incidence of prolonged pregnancy. However, these associated clinical conditions do not appear to be causal and thus their predictive power is limited. For instance, the association of low socioeconomic status with an increased incidence of postdatism may reflect delayed initiation of prenatal care and the subsequent use of less accurate dating criteria, rather than a true causal relationship with postdate pregnancy.
Properly timed initiation of labor is a complex process requiring appropriate interactions of the fetal hypothalamo-hypophyseal-adrenal axis, the placenta, fetal membranes, decidua, uterine myometrium, and cervix. Failure to coordinate these interactions impedes labor; several different pathogenic mechanisms may thus result in postdate pregnancy. Simply stated, interactions between the endocrine systems of fetus, placenta, and mother must induce anatomic and functional changes in uterine musculature and cervical resistance. The uterus is transmuted from a quiescent organ suited to retaining its contents to one that actively and rhythmically works to expel the fetus.
Activation of the myometrium is hormonally mediated by withdrawal of inhibitors of myometrial activity. For example, nitric oxide acts to relax the myometrium. At term, levels of messenger ribonucleic acid encoding inducible nitric oxide are decreased.14 The possible role of progesterone withdrawal, a mechanism well established in labor activation in many mammalian species, remains elusive. Whereas no measurable changes in progesterone occur during the phase of uterine activation, the ability of progesterone to maintain uterine relaxation could wane if antagonists to progesterone action increase. The myometrium is rendered more responsive to stimulation of stretch receptors and begins to generate the high-frequency, high-amplitude electrical signals that result in co-ordinated contractions. Once activated, the uterus also is more receptive to stimulation by prostaglandins and oxytocin.
The fetal hypothalamo-hypophyseal-adrenal axis also must be activated to effect regular contractions. The maturation, size, and function of the fetal adrenal medulla and the provisional zone of the adrenal cortex depend on the release of adrenocorticotropin from the fetal anterior pituitary.15 Adrenocorticotropic hormone also regulates fetal adrenal production of steroid hormones. As cortisol levels increase at term, cortisol increasingly competes with progesterone for binding sites on the glucocorticoid receptor.16 Increased production of other steroid hormones has been described before the onset of labor in normal human pregnancy.17 These increases are absent in anencephalic pregnancies.18 The fetal adrenal appears to be critical in timing the onset of labor because anencephalics with normal fetal adrenal cortical regions usually deliver at or before the due date, whereas those with adrenal hypoplasia classically have a postdate delivery.1 Drost and Holm19 adrenalectomized fetal sheep and were able to prolong pregnancy, whereas McDonald and Nathanielsz20 prolonged ovine gestation by ablation of the fetal paraventricular nuclei. Labor is preceded by increased maternal cortisol levels in sheep.21 Other workers22 have been able to initiate labor by intra-amniotic instillation of cortisol in the human. However, a key difference between sheep and primate models of labor initiation lies in the ability of primate fetal adrenal cortical stimulation to produce cortisol and estrogens, whereas in the sheep estrogen is not produced.
Serum estriol levels increase with advancing gestation until 40 weeks; there is a progressive decline in estriol values that parallels the decline in amniotic fluid level when the term gestation is exceeded.23,24 Placental sulfatase deficiency, a rare and specific type of placental dysfunction, is characterized by low estriol production. Prolonged pregnancy is common in patients with placental sulfatase deficiency.25 Ballantyne proposed a role for placental dysfunction in 1902 and linked to the development of the postmaturity syndrome.26 Clifford5 further advanced the theory of placental dysfunction as a cause of postmaturity syndrome, with decreased nutrient transfer to the fetus, resulting from calcification and aging of the placenta. As the placenta ages, increased rates of placental infarction and fibrin deposition decrease placental exchange of wastes and nutrients with the maternal circulation. Placental senescence impairs the transfer of oxygen fuels and the disposition of wastes as the number of villous capillaries and intervillous spaces decline. The postdate fetus experiences a range of physiologic changes that predispose it to the development of hypoxia and acidosis. These stresses in turn activate the fetal hypothalamic-hypophyseal-adrenal axis to produce more cortisol, attempting to trigger the normal process of uterine activation and stimulation leading to labor.
Grannum and coworkers27 advocate using sonography to grade the severity of placental aging on a scale of 0 to 3. A grade 3 placenta exhibits sonographic findings of linear echogenic densities, probably representing areas of increased calcium deposition, dividing the placental bed into compartments. Echolucent areas may be seen in the central portion of the compartments. The incidence of grade 3 placentas increases after 40 weeks, but its presence alone cannot be used to predict the occurrence of fetal distress or the postmaturity syndrome. However, Yeh and colleagues28 found that the postmaturity syndrome was more common when both oligohydramnios and a grade 3 placenta were present.
The amniotic fluid volume declines by as much as 33% per week in the postdate pregnancy.29 As placental blood flow decreases, the fetus must redistribute a decreased circulating blood volume to maintain renal blood flow. Diminished fetal ventricular function may also hamper the fetus's efforts to maintain renal perfusion.30 As renal blood flow decreases, so does fetal urinary output. Eventually, the decrease in amniotic fluid leads to umbilical cord compression. Intermittent cord compression can be diagnosed by identifying the presence of variable decelerations during fetal heart rate testing. Cord compression stimulates the passage of meconium by the same vagal reflex that initiates a heart rate deceleration. Meconium passed into a small amniotic fluid volume tends to be thicker, more tenacious, and more difficult to clear after aspiration. A significant amount of cord compression can lead to hypoxia, acidosis, and fetal distress. A fetus already compromised by other factors such as diabetes, hypertension, or intrauterine growth retardation has few reserves available to protect it against the additional stresses imposed by the physiologic changes occurring in the postdate pregnancy. They are particularly at risk for increased perinatal mortality.
Although placental function decreases in the postdate pregnancy, the total placental area increases so that the exchange of nutrients usually continues to support fetal growth. Therefore, the most common problem associated with postdatism is not postmaturity syndrome but macrosomia. Birth weights in excess of 4000 g are threefold to sevenfold more common in the postdate pregnancy,2 with an overall incidence of 25% at 42 weeks. The delivery of macrosomic infants is associated with increased rates of labor dystocia, birth trauma, cesarean section, and neonatal complications such as hypoglycemia, temperature instability, and jaundice. In a large review of shoulder dystocia, 40% of the cases were noted to occur in the postdate infant.31 In deciding whether to use a liberal policy of induction in the postdate population to decrease the development of macrosomia, the clinician should recognize that there is a crossover point at which the increased cesarean section rate associated with failed induction would negate any advantage of preventing a cesarean section performed for macrosomia.
Although ultrasound may be helpful in identifying macrosomic infants at risk for birth trauma, clinicians should be aware of the limitations of this modality in predicting birth weight. The formulas currently used to estimate fetal size are less accurate in macrosomic infants because of variations in head shape and adiposity found in this group. Formulas predicted on estimates of macrosomic populations or which depend less on fetal head size may carry greater accuracy in identifying the fetus at risk for shoulder dystocia.32
Intrauterine asphyxia results from a deficit in the required amount of oxygen being delivered to the fetus. The deficit results from chronic conditions such as uteroplacental insufficiency or from acute, intermittent cord compression seen in conjunction with oligohydramnios. Pregnancies complicated by chronic hypertension or diabetes mellitus, already compromised by suboptimal placental function before term, carry a fourfold to fivefold greater risk of perinatal mortality when allowed to continue after the delivery date.12 The clinical manifestations of asphyxia may range from fairly mild symptoms like the presence of variable decelerations to the development of permanent neurologic sequelae. Antepartum testing is meant to detect the fetus with hypoxia, but often a dysmature or otherwise compromised fetus exists in a prehypoxic state. Tests that could consistently identify the prehypoxic fetus at risk for asphyxia would allow this group to be delivered before complications arise. Estriol levels correlate inversely with the rate of fetal heart rate decelerations and the occurrence of fetal distress,24 but the inconvenience of performing frequent 24-hour urine collections has led to the use of other predictive tests such as the amniotic fluid index. The reliable identification of a subset of postdate pregnancies at risk for fetal hypoxia and asphyxia obviates routine induction in the low-risk postdate patient.
The mechanisms of meconium passage described earlier are more likely to be found in the postdate pregnancy. The meconium also is likely to be thicker and more tenacious because of the frequency of oligohydramnios. Meconium aspiration is eight times more common in postdatism, and its complications include pneumonia, pneumothorax, a requirement for assisted ventilation, and the development of pulmonary hypertension.33 The intrapartum identification of meconium should be accompanied by preparations to suction both the mouth and nares to clear meconium from the pharynx before delivery of the fetal body. Personnel trained in neonatal intubation should be available to intubate and continue suctioning as required. Intrapartum meconium aspiration can be decreased by the use of saline amnioinfusion, which dilutes the meconium and helps to prevent occlusion of the respiratory passages.34 An intrauterine pressure catheter is used to introduce a specific bolus amount of saline solution, followed by a variable rate of infusion as determined by baseline uterine tonus. The pressure catheter continues to provide accurate readings of the intrauterine pressure being generated by contractions.
The hallmarks of the postmature infant as described by Clifford5 include meconium staining, loss of subcutaneous fat reserves, and skin peeling. The infant's appearance is like that of a wizened old gnome—long, thin, and wrinkled with decreased muscle mass and long nails on the toes and fingers. The decreased stores of fat and glucose predispose these infants to metabolic disturbances such as hypoglycemia, hypothermia, and polycythemia. Currently, there is no way of predicting in utero which infants will develop the syndrome, although it is more commonly seen after 42 weeks and in conjunction with oligohydramnios.
Early reports suggest that the postmature infant experienced quantifiable delays of either mental or physical development that lasted up to the fifth year of life.35,36 Mothers reported increased incidence of sleep and feeding difficulties. However, other studies that used rigorous pregnancy dating criteria and stratified infants based on their Clifford staging showed that once the infant passed the perinatal period, its development was comparable with term control infants.37,38
The development of simple, reliable methods for fetal surveillance, the use of ultrasound to determine fetal size and amniotic fluid volume, and the introduction of cervical ripening agents have improved the clinician's ability to manage the postdate pregnancy safely. Before the introduction of adequate methods of fetal surveillance in the 1970s, routine induction of labor at 42 weeks was commonly practiced to improve the perinatal outcome.39,40 This management strategy predictably led to a high incidence of cesarean section for failed induction of labor, and many practitioners began to advocate expectant management for patients with an unfavorable cervix and who were at low risk for poor perinatal outcome.41 However, before the late 1970s, reliable methods for differentiating pregnancies at risk from those in which expectant management could safely be practiced did not exist. The fear of complications of macrosomia and difficulty in predicting labor dystocia and shoulder dystocia associated with this complication may have contributed to higher than necessary cesarean section rates until newer technology allowed better differentiation of the macrosomic fetus. Postdate patients with an unfavorable cervix have benefitted from the introduction of cervical ripening agents. Prostaglandin preparations to ripen the cervix are available as a gel (dinoprostone [Prepidil]), removable sustained release suppository (Cervidil), or as a vaginal tablet (misoprostol). These agents sensitize the uterus to the action of uterotonic agents, as well as remodel the cervix, and have encouraged physicians to undertake induction of labor in postdate patients when delivery is indicated.
The development of simple, inexpensive, and easily interpreted methods of antepartum fetal testing has led to the current practice of watchful waiting in patients with an unfavorable cervix and reassuring antepartum test results, reserving routine induction for patients with an inducible cervix, nonreassuring test results, or other risks for a poor outcome. Antepartum surveillance generally begins at 41 weeks, or 287 days from the first day of the last menstrual period, because the perinatal morbidity and mortality begin to rise before 42 weeks of amenorrhea.42,43 Several antenatal surveillance schemes are in current use44,45,46,47,48,49 (Table 1). The ideal test would be easily administered and easily interpreted, noninvasive, cost effective, sensitive enough to identify the fetus at risk, and yet specific enough to prevent excessive intervention. Use of the contraction stress test, the nonstress test, or the biophysical profile for antepartum testing decreases the perinatal morbidity and mortality associated with postdatism. The relative merits of each testing scheme have led to considerable debate as to which is the single “best” test.
BP, blood pressure; CTX, contractions; FHR, fetal heart rate.
The contraction stress test remains the gold standard for antepartum fetal surveillance.4,50 Freeman44 conducted a prospective study of over 700 postdate pregnancies using weekly contraction stress testing to identify fetuses at risk for intrapartum distress. There were no perinatal deaths using this methodology. However, only 57.9% of patients had a normal result for the last test before delivery. Many (38.5%) patients had equivocal test results that required either frequent retesting or other intervention. Although the low rates of perinatal mortality and morbidity achieved using the contraction stress test attest to its sensitivity, the high percentage of equivocal results obtained can make the test cumbersome to administer to numerous patients. The test also frequently requires the intravenous administration of oxytocin, although sometimes this can be obviated by use of nipple stimulation rather than oxytocin infusion. The nonstress test now is the most widely used method of antepartum fetal surveillance because of its simplicity and noninvasive nature. Analysis of a fetal heart tracing requires the identification of accelerations, spontaneous decelerations, baseline heart rate, and uterine activity before classifying the tracing as reactive, reactive with decelerations, or nonreactive. Fetal stimulation by palpation or the use of vibroacoustic stimuli can be used to induce reactivity without compromising the validity of the test. When the nonstress test is performed weekly, perinatal outcome is not as favorable as when the contraction stress test is performed weekly.45 Performance of the test twice weekly improves perinatal outcome.51 Recently, estimation of the amniotic fluid volume in conjunction with the use of the nonstress test has been advocated as an acceptable alternative to a weekly contraction stress test.52 The biophysical profile48 is unique in its primary reliance on ultrasound parameters rather than fetal heart rate patterns. A normal biophysical profile with all ultrasound parameters identified during the test period of 30 minutes was associated with no perinatal mortality and low rates of perinatal morbidity. An abnormal test requires the use of nonstress testing in addition to ultrasound, with appropriate intervention predicated on the results of the nonstress test.
Doppler velocimetry studies have not been helpful in identifying the postdate infant at risk for intrapartum distress, perhaps because the umbilical arterial and venous diameters are increased in the postdate fetus.53 Recently, some have advocated that middle cerebral artery velocity or a ratio between middle cerebral and umbilical arterial velocities has been helpful in identification of the fetus most at risk for complications from postdate pregnancy.54
Use of Ultrasound
Fetal macrosomia occurs at least three times more frequently in postdate pregnancy than in term deliveries.2 There is increased morbidity to both mother and infant because of an increased frequency of birth trauma and cesarean delivery. Approximately 40% of shoulder dystocia cases occur in postterm deliveries.55 Use of ultrasound to estimate fetal weight represents a significant improvement over clinical estimation of fetal size by the Leopold method56 because it is less dependent on the mother's size and the skill of the examiner. However, the formulas currently available for estimation of fetal size are less accurate in the upper range of the birth weight spectrum because of fetal variation in head shape, adiposity, and muscle mass. The average margin of error is 10% to 15%. Even when this margin remains stable, the absolute value of the difference between estimated and actual weight is greater in larger infants. Ultrasound identification of a fetus with an estimated weight in excess of 4500 g should prompt the physician to consider cesarean delivery, although this remains controversial.
Once the timing and route of delivery has been selected, the clinician may be stymied by the presence of an unfavorable cervix. Most patients with documented postterm pregnancy have a low Bishop score.57 When expectant management is no longer an option, cervical ripening techniques may help to attain a safe vaginal delivery. Membrane stripping by vigorous cervical examination is a widely practiced technique that many practitioners subjectively believe decreases the incidence of postdate pregnancy.58 Theoretically, a low-grade deciduitis ensues and leads to the initiation of labor by release of prostaglandins near the cervical os. A prospective study involving 180 subjects was conducted in which women were randomized to either gentle cervical examination to assess Bishop score or to vigorous membrane stripping. The authors found a statistically decreased frequency of postterm delivery in patients who had undergone membrane stripping.59 Laminaria tents quickly accomplish the goal of cervical dilation but have been associated with a higher incidence of infectious complications such as neonatal group B streptococcal infection.60 Synthetic laminaria do not appear to be associated with increased infectious morbidity, but their efficacy as cervical ripening agents in postterm pregnancy has not been studied widely. The use of a Foley catheter, relaxin, or breast stimulation also has been advocated for cervical priming.59
Prostaglandin E2 appears to be the most promising cervical ripening agent to become available during the last decade. Dyson and coworkers61 conducted a prospective randomized trial involving 302 patients with documented postdate pregnancies and unfavorable Bishop scores. Rates of meconium passage, fetal distress, duration of labor, and cesarean section were higher in the group assigned to expectant management with antepartum testing than in the group who received intravaginal or intracervical prostaglandin gel as outpatients. However, other studies have not shown benefit.62 Great variation exists in the dosage, timing, and route of administration of prostaglandin gel. Even the type of gel used to suspend the prostaglandin may affect the rate of systemic absorption. Rapid absorption is associated with uterine hyperstimulation and fetal distress that may be difficult to treat because prostaglandin, once administered, cannot be removed easily. In summary, prostaglandin gel appears to be a reasonable adjunctive therapy in selected patients with unfavorable cervix who are to undergo induction of labor. Once the cervical priming is complete, amniotomy or oxytocin administration may be used to stimulate labor.
The postdate fetus enters the labor process with little uteroplacental reserve and may rapidly become hypoxic or asphyxiated. Fetal heart rate patterns reflect the fetus's ability to withstand the stresses of intermittent hypoxia and may be classified as reassuring or nonreassuring. In general, a normal baseline fetal heart rate with good variability or a pattern of spontaneous deceleration with rapid recovery and good interval variability are indicative of a fetus who is tolerating labor without any ominous problems. Spontaneous variable decelerations are indicative of intermittent cord compression and can be seen frequently either in labor or during antepartum testing. The presence of variable decelerations is associated with oligohydramnios. Late decelerations are suggestive of uteroplacental insufficiency and are associated with increased rates of fetal distress, low Apgar scores, and perinatal morbidity. Persistent late decelerations, especially when associated with a loss of reactivity, are particularly ominous. A fetus displaying such a fetal heart rate pattern requires expeditious delivery in an environment equipped for neonatal resuscitation. Maternal positional changes, hydration, and oxygen administration may alleviate fetal heart rate patterns associated with intermittent cord compression. Recently, the use of saline amniofusion has decreased the rate of cesarean delivery performed for fetal distress and the rate of meconium aspiration.34,63 The obstetrician should be alert to the probability of meconium passage by the postdate infant and be ready to aggressively suction the nasopharynx and oropharynx after delivery of the fetal head. Fetal scalp blood sampling may be of value in identifying an acidotic fetus, but when acidosis is diagnosed, it may be a transient respiratory acidosis of little clinical significance rather than a metabolic acidosis.64 Additionally, fetal scalp puncture may lead to hemorrhage, scalp infection, and increased rates of vertical transmission of human immunodeficiency virus or hepatitis to the fetus.
These techniques combined with appropriate induction of labor allow many women to experience a safe vaginal delivery. Cesarean delivery still is required for many women with a postterm pregnancy; the perinatal morbidity of the procedure should be weighed against the likelihood of fetal asphyxia and birth trauma before proceeding. Use of prophylactic antibiotics can reduce the rate of endometritis and postoperative febrile morbidity.
Whereas the diagnosis of postdatism remains a challenge, the clinician's ability to identify a potentially compromised fetus has been improved by the introduction of reliable antepartum surveillance methods. The most important controversy that needs to be addressed is the issue of whether to use routine induction for all postdate patients or to selectively induce patients who have favorable cervices, nonreassuring antepartum test results, macrosomia, or other antepartum complications. Although physicians differ in their beliefs as to the reliability of antepartum testing in preventing all perinatal complications and in the likelihood of success using prostaglandin cervical ripening, evidence indicates that the use of routine induction in the postdate pregnancy leads to a significantly increased rate of cesarean section without a concomitant improvement in outcome. Watchful waiting can safely be used in most postdate pregnancies with normal antepartum test results and without other risk factors, and the subset of women who require delivery can be reliably predicted using current methodology. Ultrasound can improve the selection of women in whom a vaginal delivery may lead to increased birth trauma. The introduction of various cervical ripening techniques holds promise to decrease rates of failed labor induction. Finally, intrapartum treatment of fetal heart rate abnormalities may decrease the rates of cesarean section for fetal distress and for meconium aspiration syndrome. A satisfactory outcome can be reasonably expected in the postdate pregnancy managed appropriately.
16. Patel FA, Clifton VL, Chwalisz K et al: Steroid regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua in relation to labor. J Clin Endocrinol Metab 84: 291, 1999
25. Flint APT: Regulation of placental enzymes. In MacDonald PD, Porter JC (eds): Initiation of Parturition: Prevention of Postmaturity. Fourth Ross Conference on Obstetrics Research. Columbus, OH, Ross Laboratories, 1983
36. Field T, Dempsey J, Shumann HH: Five year follow-up of preterm respiratory distress syndrome and post-term postmaturity infants. In Field T, Sostek (eds): Infants Born at Risk. Philadelphia, Grune & Stratton, 1983