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Postdates and Antenatal Testing
Postdates and Antenatal Testing Michael Y. Divon, MD, and Noa Feldman-Leidner, MD The standard definition of a prolonged pregnancy is 42 completed weeks of gestation. The incidence of prolonged pregnancy varies depending on the criteria used to define gestational age at birth. It is estimated that 4 to 19% of pregnancies reach or exceed 42 weeks gestation. Several studies that have used very large computerized databases of well-dated pregnancies provided insights into the incidence and nature of adverse perinatal outcome such as an increased fetal and neonatal mortality as well as increased fetal and maternal morbidity in prolonged pregnancy. Fetal surveillance may be used in an attempt to observe the prolonged pregnancy while awaiting the onset of spontaneous labor. This article reviews the different methodologies and protocols for fetal surveillance in prolonged pregnancies. On the one hand, false-positive tests commonly lead to unnecessary interventions that are potentially hazardous to the gravida. On the other hand, to date, no program of fetal testing has been shown to completely eliminate the risk of stillbirth. Semin Perinatol 32:295-300 © 2008 Elsevier Inc. All rights reserved. KEYWORDS prolonged pregnancy, fetal testing, perinatal morbidity, prenatal mortality, nonstress test, biophysical profile, Doppler
Prolonged Pregnancy
T
he standard definition of a prolonged pregnancy is 42 completed weeks of gestation. This definition is endorsed by the American College of Obstetricians and Gynecologists, The World Health Organization, and the International Federation of Gynecology and Obstetrics.1-3 In view of more recent perinatal mortality data that were derived from accurately dated pregnancies, it would be reasonable to conclude that prolonged pregnancy should be defined as gestational age at birth greater than or equal to 41 weeks of gestation. The incidence of prolonged pregnancy varies depending on the criteria used to define gestational age at birth. It is estimated that 4 to 19% of pregnancies reach or exceed 42 weeks gestation and 2 to 7% complete 43 weeks of gestation.
Prolonged Pregnancy as an Indication for Fetal Testing Several studies that have used very large computerized databases of well-dated pregnancies provide insights into the incidence and nature of adverse perinatal outcome in proDepartment of Obstetrics and Gynecology, Lenox Hill Hospital, New York, NY. Address reprint requests to Michael Y. Divon, MD, Department of Obstetrics and Gynecology, Lenox Hill Hospital, 130 E. 77th St., New York, NY 10075. E-mail: [email protected]
0146-0005/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.semperi.2008.04.013
longed pregnancy. Divon and coworkers evaluated fetal and neonatal mortality rates in 181,524 accurately dated term and prolonged pregnancies.4 Their study documented a small but significant increase in fetal mortality in accurately dated pregnancies that extend beyond 41 weeks gestation and demonstrated that fetal growth restriction is independently associated with a large increase in perinatal mortality in these pregnancies. These results were confirmed by other investigators.5,6 Clausson and coworkers documented that perinatal mortality rates in small for gestational age fetuses had higher odds ratio for stillbirth and neonatal death.6 The stillbirth rate did not change significantly when fetuses with congenital malformations were excluded. However, an 80% drop in neonatal deaths occurred when malformed neonates were excluded from the analysis. In addition, prolonged pregnancies were associated with an increased frequency of neonatal convulsions, meconium aspiration syndrome, and Apgar score of ⬍4 at 5 minutes. Again, morbidity in postterm small for gestational age (SGA) infants was higher than in postterm AGA infants. Further support for the concept that the “small and old” fetus suffers from increased perinatal mortality was provided by Campbell and coworkers, who performed a multivariate analysis of factors associated with perinatal death among 65,796 singleton postterm (ⱖ294 days) births.7 Three variables were identified as independent predictors of perinatal mortality. SGA and maternal age equal or greater than 35 years were associated with a significant increase in perinatal mortality. Interestingly, large for gesta295
296 tional age status (ie, birth weight ⱖ90th percentile for gestational age) was associated with a modest protective effect for perinatal death. However, macrosomia was associated with a higher incidence of labor dysfunction, obstetrical trauma, shoulder dystocia, and maternal hemorrhage. Several studies have shown that the incidence of macrosomia increases with advancing gestational between 37 and 43 weeks. In addition, this increase also results in doubling the cesarean rate for protraction or descent disorders.8-10 There is good evidence to suggest that fetal and maternal morbidity are also increased as gestational age advances beyond term. Tunon and coworkers compared neonate intensive care unit (NICU) admission rates among 10,048 term pregnancies and 246 prolonged pregnancies (ⱖ296 days by both scan and last menstrual period (LMP) dates).11 Prolonged pregnancy was associated with a significant increase in NICU admissions (odds ratio, 2.05; 95% CI, 1.35 and 3.12). Several maternal and fetal complications were evaluated in a large (n ⫽ 45,673) retrospective, cohort study by Caughey and Musci.12 The authors concluded “that risks to both mother and infant increase as pregnancy progresses beyond 40 weeks’ gestation, and that antenatal fetal testing should begin sooner than current recommendation of 42 weeks of gestation.” Olesen and coworkers evaluated a large computerized Danish database of singleton, live-born term and postterm (⬎42 weeks) deliveries to quantify maternal and fetal risks associated with postterm delivery.13 Both perinatal and maternal complications were increased significantly in postterm deliveries.
Fetal Surveillance Fetal surveillance may be used in an attempt to observe the prolonged pregnancy safely while awaiting the onset of spontaneous labor. On the one hand, false-positive tests commonly lead to unnecessary interventions that are potentially hazardous to the gravida. On the other hand, to date, no program of fetal testing has been shown to completely eliminate the risk of stillbirth. Data presented earlier in this review indicate that perinatal mortality is significantly increased as early as 41 weeks gestation and possibly even earlier. The optimal gestational age for the initiation of fetal testing has not been established. Jazayeri and coworkers provided physiologic evidence of altered fetal oxygenation in patients at ⱖ41 weeks by demonstrating elevated plasma erythropoietin levels in these patients.14 Thus, it would seem prudent to initiate fetal testing at 41 weeks of gestation. Extensive experience with biophysical profile testing in high-risk populations indicates a perinatal mortality rate of 0.73 per 1000 tested pregnancies within 1 week of a normal test provided that the amniotic fluid volume is normal.15 Twice-weekly testing with the biophysical profile was reported in a series of 307 patients followed beyond 42 weeks of gestation. When the profile score was normal, waiting for
M.Y. Divon and N. Feldman-Leidner spontaneous labor resulted in healthy neonates and a much lower cesarean section rate. No stillbirths were observed in this small series.16 Several investigators have examined the efficacy of using a nonstress test (NST) as a primary testing modality with the addition of sonographic assessment of amniotic fluid. Clark and coworkers tested 279 prolonged pregnancies with this testing scheme. No stillbirths were recorded.17 Miller and coworkers reported on the use of a similar protocol in 6390 prolonged pregnancies.18 The false-negative rate of this test was 0.8 per 1000 women tested—a rate that favorably compares with those reported for the contraction stress test or the complete biophysical profile.15,19 An analysis of all false-positive tests showed that the routine use of nonstress testing combined with the amniotic fluid index (AFI) resulted in a 60% false-positive rate in the prediction of intrapartum fetal compromise compared with a 40% false-positive rate using the complete biophysical profile. This increase in false-positive tests was felt to be partly due to the poor specificity of the AFI in predicting fetal compromise. Alfirevic and Walkinshaw compared the impact on perinatal outcome of two different protocols for antenatal fetal monitoring after 42 weeks.20. One hundred forty-five women with singleton, uncomplicated pregnancies after 42 weeks of gestation were randomly allocated to fetal monitoring by either a biophysical profile combined with computerized cardiotocography or a standard cardiotocography supplemented by measurement of the largest vertical pocket of amniotic fluid. Their results documented significantly more abnormal antenatal monitoring tests in the biophysical profile combined with the computerized cardiotocography group. There were no differences in cord blood gases, neonatal outcome, or outcomes related to labor and delivery between the two groups, but there was a trend toward more obstetric interventions in the biophysical profile combined with the computerized cardiotocography group. Amniotic fluid volume after 42 weeks was more likely to be labeled as abnormal with amniotic fluid index than with largest vertical pocket. Sylvestre and coworkers evaluated the incidence of abnormal testing (NST and AFI) as a function of birth weight in 792 uncomplicated prolonged pregnancies (⬎41 weeks).21 They showed an inverse relationship between abnormal testing and birth weight. In addition, small fetuses were more likely to require a cesarean delivery for non-reassuring fetal status during labor than were all other fetuses. Thus, it is reasonable to conclude that the small, postterm fetus is not only more likely to die in utero but is also more likely to fail antepartum fetal testing and to be delivered by nonelective cesarean section for an intrapartum diagnosis of non-reassuring fetal status. The implicit assumption in the expectant management strategy is that the presence of an abnormal fetal test (such as oligohydramnios, low biophysical profile score, or spontaneous fetal heart rate decelarations) represents a change in fetal status that requires intervention in the from of prompt delivery. A novel view of the regulation of fetal homeostasis during late gestation was offered by Onyeije and Divon.22 These
Postdates and antenatal testing authors studied the incidence of maternal ketonuria (as a reflection of maternal starvation and dehydration) and its association with abnormal fetal surveillance tests. One thousand eight hundred ninety-five patients were managed expectantly with semiweekly fetal testing. Beginning at 41 weeks gestation, clinically detectable ketonuria occurred in 10.9% of patients studied. Patients with ketonuria were at increased risk for abnormal test results, including the presence of oligohydramnios (24 versus 9.3%, P ⬍ 0.0001), nonreactive NST (6.2 versus 2.15%, P ⬍ 0.0001), and the presence of fetal heart rate decelerations (14 versus 9.2%, P ⬍ 0.0039). The authors suggested that reversible maternal ketonuria contributes to the false-positive test results often encountered in fetal testing, and that such patients might benefit from treatment of ketonuria rather than be delivered in response to the abnormal test results. The formation of amniotic fluid is a complex and poorly understood process. Multiple authors have demonstrated that amniotic fluid volume decreases as gestational age advances beyond 32 or 34 weeks gestation. Marks and Divon evaluated the AFI in 511 well-dated prolonged pregnancies.23 Gestational age at the time of the study ranged from 41 weeks to 43 weeks and 6 days. AFI measurements ranged from 1.7 to 24.6 cm, with a mean and standard deviation of 12.4 ⫾ 4.2 cm at 41 weeks. Oligohydramnios (AFI ⬍5.0 cm) was detected in 11.5% of the study population. Longitudinal data were available from 121 patients. These patients demonstrated a mean decrease in AFI of 25% per week. Thus, the authors concluded that the majority of pregnancies at ⱖ41 weeks gestation have a normal volume of amniotic fluid. In the absence of ruptured membranes or fetal urinary tract abnormalities, diminishing levels of amniotic fluid volume may be related to poor placental function.24 Trimmer and coworkers detected diminished urine production in pregnancies of 42 weeks or more with oligohydramnios and suggested that decreased fetal urine production was the result of preexisting oligohydramnios, which limited fetal swallowing of amniotic fluid rather than a decrease in renal perfusion.25 Bar-Hava and coworkers used pulsed-wave Doppler to evaluate resistance index values in the fetal middle cerebral artery, renal, and umbilical arteries in 57 pregnancies at ⱖ41 weeks gestation.26 It was expected that, with hypoxia, impedance in the cerebral circulation might decrease as impedance increased in the renal circulation. Oligohydramnios (AFI ⬍5 cm) was detected in 15 patients. The various resistance index values and the ratios among them were not significantly different in patients with or without oligohydramnios. Interestingly, the mean birth weight in patients with oligohydramnios was significantly lower than the mean birth weight in patients with a normal AFI. The authors concluded that oligohydramnios in these patients is not associated with a noticeable redistribution of blood flow and suggested that the cause of oligohydramnios is probably unrelated to renal perfusion. The fact that oligohydramnios was found more often in the smaller fetuses is intriguing. It suggests that the appearance of oligohydramnios is a pathologic rather than a physiologic
297 process. It may indicate that the pathophysiology of oligohydramnios in prolonged pregnancy is similar to that involved with the formation of oligohydramnios in the growth-restricted fetus, and overall it is consistent with the concept that it is the small and “older” fetus that is more prone to complications arising from asphyxia. Leveno and coworkers used the presence of oligohydramnios to explain the increased incidence of abnormal antepartum and intrapartum fetal heart rate (FHR) abnormalities seen in prolonged pregnancies.27 These authors suggested that prolonged FHR decelerations representing cord compression preceded 75% of cesarean deliveries for fetal jeopardy. The association between reduced amniotic fluid index and variable decelerations is well documented, as suggested by Gabbe and coworkers, and variable FHR decelerations detected in patients with oligohydramnios are probably related to increased umbilical cord compression.28 Both Phelan and coworkers and Divon and coworkers found that the frequency of nonstress tests demonstrating FHR decelerations or bradycardia increased as the ultrasonographic estimates of the amniotic fluid declined.29-31 The use of an amniotic fluid index ⱕ5.0 cm to define oligohydramnios was first suggested by Phelan and coworkers in 1987, as an arbitrary cutoff value based on retrospective studies. Nevertheless, it has since gained popular appeal.29,30 A meta-analysis evaluated the risk of cesarean delivery for fetal distress, 5-minute Apgar score of ⬍7, and umbilical artery pH ⬍7.00 in patients with antepartum or intrapartum AFI ⬍5.0 cm.32 Eighteen reports describing 10,551 patients at various gestational ages were included in the analysis. The overall incidence of oligohydramnios was 15.2%. The authors concluded that an AFI ⱕ5.0 cm is associated with an increased risk of cesarean delivery for fetal distress (relative risk of 2.2; 95% CI, 1.5-3.4) and an Apgar score of ⬍7 at 5 minutes (relative risk of 5.2; 95% CI, 24113). However, no association was demonstrated between oligohydramnios and severe fetal acidosis. A prospective, blinded observational study of the usefulness of ultrasound assessment of amniotic fluid in the prediction of adverse outcome in the prolonged pregnancy was reported by Morris and coworkers.33 The authors demonstrated that AFI ⬍5 cm was significantly associated with adverse perinatal outcome. Despite these associations, the sensitivity of an AFI ⬍5 cm was very low, ranging from 11.5 to 28.6 for major adverse outcome, fetal distress in labor, or admission to the NICU. The authors concluded that “routine use is likely to lead to increased obstetric intervention without improvement in perinatal outcome” and that large clinical trials are necessary to assess the effectiveness of delivery based on sonographically diagnosed oligohydramnios. In a recent study Lam and coworkers evaluated the usefulness of AFI in the fetal surveillance of postdate pregnancies.34 The authors concluded that “although AFI may be used to predict the occurrence of thick meconium stained liquor and the need for intervention for fetal distress in postdate pregnancies, its role on its own is limited.” The presence of sonographically diagnosed oligohydramnios is often used as an indication for delivery of pregnancies
M.Y. Divon and N. Feldman-Leidner
298 that reach term gestation or extend beyond term. One should however realize that up to 50% of patients, who are diagnosed by ultrasound as having oligohydramnios, will have a normal volume of amniotic fluid on artificial rupture of the membranes.35 In addition, there are no large-scale prospective randomized studies documenting the benefits of delivery once oligohydramnios has been diagnosed. In the absence of such studies, it would seem prudent to deliver patients at or beyond 41 weeks gestation who demonstrate oligohydramnios primarily because of the large body of data which documents an association between diminished amniotic fluid volume and adverse perinatal outcome. Doppler velocimetry is often used to identify fetal compromise due to altered fetal circulation. Its role in establishing fetal well-being in prolonged pregnancies is unclear. Several studies have concluded that the use of umbilical artery Doppler velocimetry is not associated with an improvement of the positive-predictive value of fetal testing in prolonged pregnancy.36-39 Zimmermann and coworkers performed a fetal Doppler cross-sectional, prospective study in 153 pregnancies beyond 287 days of gestation (36% were followed beyond 42 weeks of gestation).39 The resistance indices of the umbilical artery and the middle cerebral artery waveforms were studied every 2 days until delivery. All velocities fell within the known 95% confidence intervals for normal term fetuses. Doppler measurements were unable to predict adverse fetal outcomes, such as abnormal fetal heart rate tracings, thick meconium, the need for urgent operative delivery, acidemia at delivery, or neonatal encephalopathy. In contrast, Oz and coworkers studied 147 well-dated, singleton, postterm pregnancies, of which 21 (14.3%) had oligohydramnios.40 The authors assessed the correlation between renal and umbilical artery Doppler velocimetry, and oligohydramnios. They demonstrated that the renal artery resistance index was significantly higher in cases with oligohydramnios. A renal artery Doppler end-diastolic velocity below the mean for gestational age significantly increased the risk of oligohydramnios (relative risk of 1.5 with 95% CI of 1.1-2.0). Their findings support the hypothesis that increased arterial impedance is an important factor in the development of oligohydramnios in prolonged pregnancies. Two other studies support these findings.41,42 Recently, Lam and coworkers in a prospective observational study of 118 uncomplicated postdated pregnancies at 41 weeks evaluated the distribution of fetal cerebro-placental Doppler indices and amniotic fluid volume.41 The correlation with the incidence of passage of thick meconium in labor was analyzed. The middle cerebral artery pulsatility index was found to be significantly better than amniotic fluid volume or umbilical artery pulsatility index in predicting the risk of thick meconium-stained liquor in labor. Figueras and coworkers in a prospective study of prolonged pregnancies evaluated the value of middle cerebral artery Doppler indices obtained from different sampling sites in predicting umbilical cord gases at delivery.42 Fifty-six patients were included in the final analysis. The proximal middle cerebral artery pulsatility index was found to significantly predict umbilical artery pO2 at delivery but did not predict pH.
In conclusion, given the information available at the present time, it is difficult to define the extent to which the use of Doppler velocimetry can improve the positive-predictive value of fetal testing in prolonged pregnancy. Sonographic fetal weight estimates are often obtained as part of fetal testing in prolonged pregnancies. The accurate and timely prediction of macrosomia may well influence delivery management decisions. However, one should note that the accurate estimation of fetal weight must be viewed in its broad clinical context of feto-pelvic disproportion. Thus, the crucial factor is the relationship of the fetal size to the maternal pelvis rather than the common clinical preoccupation with macrosomia alone. Focusing on either one of these factors in isolation represents a conceptual error.43 Traditionally, obstetricians have predicted fetal weight by abdominal palpation or symphysialfundal height measurement. Ultrasound failed to fulfill the expectation for a more accurate method to estimate fetal weight. Both Chervenak and coworkers and Pollack and coworkers documented that a sonographic estimate of fetal weight of ⬎4000 g had low sensitivity and low positivepredictive value and, therefore, the authors concluded that routine sonographic screening for macrosomia in prolonged pregnancies is associated with relatively low accuracy.43-45 In an attempt to improve the accuracy of sonographic estimates of fetal weight, O’Reilly-Green and Divon used receiver operating characteristic curve analysis to identify optimal cutoff values of estimate of fetal weight in the prediction of macrosomia in prolonged pregnancies.46 The authors concluded that cutoff values derived from their analysis resulted in reasonable sensitivities but disappointingly low positive-predictive values. The practical implications of the low predictive value of ultrasonography have been highlighted by Rouse and coworkers. These authors have shown that in nondiabetic pregnancies the level of intervention and the economic costs of prophylactic cesarean delivery for fetal macrosomia diagnosed by mean of ultrasonography would be excessive.47,48 It would seem reasonable that as fetal weight continues to increase with advancing gestational age, delivery of those pregnancies with a potential for macrosomia might prevent some cases of shoulder dystocia and a subsequent brachial plexus injury. However, this intervention could be achieved only by increasing the rate of inductions of labor or by an increased use of cesarean deliveries, both of which would subject the patient to added morbidity or even unnecessary mortality.
Summary Management of the prolonged pregnancy is primarily determined by the interplay of three factors: certainty of gestational dating, the risks associated with expectant management, and the likelihood of spontaneous vaginal delivery following an induction of labor. A Cochrane Database of Systematic Review from 2007 assessed the effects of interventions aimed at either reducing the incidence or
Postdates and antenatal testing improving the outcome of postterm pregnancy. Twentysix trials of variable quality were included.49 The author concluded that routine early pregnancy ultrasound examination and subsequent adjustment of delivery date appear to reduce the incidence of postterm pregnancy. Furthermore, routine induction of labor after 41 weeks gestation appears to reduce perinatal mortality. However, there was not enough evidence to evaluate the effects of antenatal testing on fetal wellbeing.
References 1. American College of Obstetricians and Gynecologists (ACOG): American College of Obstetricians and Gynecologists Practice Bulletin. Management of Postterm Pregnancy, September 2004 2. World Health Organization (WHO): Recommended definition terminology and format for statistical tables related to perinatal period and rise of new certification for the cause of perinatal deaths. Modifications recommended by FIGO as amended, October 14, 1976. Acta Obstet Gynecol Scan 56:247-253, 1977 3. Federation of Gynecology and Obstetrics (FIGO): Report of the FIGO subcommittee on Perinatal Epidemiology and health statistics following a workshop in Cairo, November 11-18, 1984. London, International Federation of Gynecology and Obstetrics 1986, p 54 4. Divon MY, Haglund B, Nisell H, et al: Fetal and neonatal mortality in the post-term pregnancy: the impact of gestational age and fetal growth restriction. Am J Obstet Gynecol 178:726-731, 1998 5. Ingemarsson I, Kallen K: Stillbirths and rate of neonatal deaths in 76,761 postterm pregnancies in Sweden, 1982-1991: a register study. Acta Obstet Gynecol Scand 76:658-662, 1997 6. Clausson B, Cnattingius S, Axelsson O: Outcomes of post-term births: the role of fetal growth restriction and malformations. Obstet Gynecol 94:758-762, 1999 7. Campbell MK, Ostbye T, Irgens LM: Post-term birth: risk factors and outcomes in a 10-year cohort of Norwegian births. Obstet Gynecol 89:543-548, 1997 8. Boyd ME, Usher RH, McLean FH: Fetal macrosomia: prediction, risks, proposed management. Obstet Gynecol 61:715-722, 1983 9. McLean FH, Boyd ME, Usher RH, et al: Post-term infants: too big or too small? Am J Obstet Gynecol 164:619-624, 1991 10. Nahum GG, Stanislaw H, Huffaker BJ: Fetal weight gain at term: linear with minimal dependence on maternal obesity. Am J Obstet Gynecol 172:1387-1394, 1995 11. Tunon K, Eik-Nes SH, Grottum P: Fetal outcome in pregnancies defined as post-term according to the last menstrual period estimate, but not according to the ultrasound estimate. Ultrasound Obstet Gynecol 14:12-16, 1999 12. Caughey AB, Musci TJ: Complications of term pregnancies beyond 37 weeks of gestation. Obstet Gynecol 103:57-62, 2004 13. Olesen AW, Wesergaad JG, Olsen J: Perinatal and maternal complications related to postterm delivery: a national register-based study, 1978-1993. Am J Obstet Gynecol 189:222-227, 2003 14. Jazayeri A, Tsibris JC, Spellacy WN: Elevated umbilical cord plasma erythropoietin levels in prolonged pregnancies. Obstet Gynecol 92:6163, 1998 15. Manning FA, Morrison I, Harman CR, et al: Fetal assessment based on fetal biophysical profile scoring: experience in 19,221 referred highrisk pregnancies. II. An analysis of false-negative fetal deaths. Am J Obstet Gynecol 157:880-884, 1987 16. Johnson JM, Harman CR, Lange IR, et al: Biophysical profile scoring in the management of the post term pregnancy: an analysis of 307 patients. Am J Obstet Gynecol 154:269-273, 1986 17. Clark SL, Sabey P, Jolley K: Nonstress testing with acoustic stimulation and amniotic fluid volume assessment: 5973 tests without unexpected fetal death. Am J Obstet Gynecol 160:694-697, 1989 18. Miller DA, Rabello YA, Paul RH: The modified biophysical profile: antepartum testing in the 1990’s. Am J Obstet Gynecol 174:812-817, 1996
299 19. Freeman RK, Anderson G, Dorchester W: A prospective multicenter multi institutional study of antepartum fetal heart rate monitoring. II. Contraction stress test versus non-stress test for primary surveillance. Am J Obstet Gynecol 143:778-781, 1982 20. Alfirevic Z, Walkinshaw SA: A randomized controlled trial of simple compared with complex antenatal fetal monitoring after 42 weeks of gestation. Br J Obstet Gynaecol 102:638-643, 1995 21. Sylvestre G, Fisher M, Westgren M, et al: Non-reassuring fetal status in the prolonged pregnancy: the impact of fetal weight. Ultrasound Obstet Gynecol 18:244-247, 2001 22. Onyeije CI, Divon MY: The impact of maternal ketonuria on fetal test results in the setting of postterm pregnancy. Am J Obstet Gynecol 184:713-718, 2001 23. Marks AD, Divon MY: Longitudinal study of the amniotic fluid index in postdates pregnancy. Obstet Gynecol 79:229-233, 1992 24. Gresham El, Rankin JH, Makowski EL, et al: An evaluation of fetal renal function in chronic sheep preparation. J Clin Invest 51:149156, 1972 25. Trimmer KJ, Leveno KJ, Peters MT, et al: Observation on the cause of oligohydramnios in prolonged pregnancy. Am J Obstet Gynecol 163: 1900-1903, 1990 26. Bar-Hava I, Divon MY, Sardo M, et al: Is oligohydramnios in post-term pregnancy associated with redistribution of fetal blood flow? Am J Obstet Gynecol 173:519-522, 1995 27. Leveno KJ, Quirk JG Jr, Cunningham FG, et al: Prolonged pregnancy observations concerning the causes of fetal distress. Am J Obstet Gynecol 150:465-473, 1984 28. Gabbe SG, Ettinger BB, Freeman RK, et al: Umbilical cord compression associated with amniotomy: laboratory observations. Am J Obstet Gynecol 126:353-355, 1976 29. Phelan JP, Smith CV, Broussard P, et al: Amniotic fluid volume assessment with the four-quadrant technique at 36-42 weeks’ gestation. J Reprod Med 32:540-542, 1987 30. Phelan JP, Ahn MO, Smith CV, et al: Amniotic fluid index measurements during pregnancy. J Reprod Med 32:601-604, 1987 31. Divon MY, Marks AD, Henderson CE: Longitudinal measurement of amniotic fluid index in postterm pregnancies and its association with fetal outcome. Am J Obstet Gynecol 172:142, 1995 32. Chauhan SP, Sanderson M, Hendrix N, et al: Perinatal outcome and amniotic fluid index in the antepartum and intrapartum periods: a meta-analysis. Am J Obstet Gynecol 181:1473-1478, 1999 33. Morris JM, Thompson K, Smithey J, et al: The usefulness of ultrasound assessment of amniotic fluid in predicting adverse outcome in prolonged pregnancy: a prospective blinded observational study. BJOG 110:989-994, 2003 34. Lam H, Leung WC, Lee CP, et al: Amniotic fluid volume at 41 weeks and infant outcome. J Reprod Med 2006 6:484-488, 2006 35. O’Reilly-Green CP, Divon MY: Predictive value of amniotic fluid index for oligohydramnios in patients with prolonged pregnancies. J Matern Fetal Med 5:218-226, 1996 36. Strokes HJ, Roberts RV, Newnham JP: Doppler flow velocity waveform analysis in postdate pregnancies. Aust NZ J Obstet Gynecol 31:27-30, 1991 37. Guidetti DA, Divon MY, Cavalieri RL, et al: Fetal umbilical artery flow velocimetry in postdate pregnancies. Am J Obstet Gynecol 157:15211523, 1987 38. Farmakides G, Schulman H, Ducey J, et al: Uterine and umbilical Doppler velocimetry in post term pregnancy. J Reprod Med 33:259261, 1988 39. Zimmermann P, Albck T, Koskinen J, et al: Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy. Ultrasound Obstet Gynecol 5:189-197, 1995 40. Oz AU, Holub B, Mendilcioglu I, et al: Renal artery Doppler investigation of the etiology of oligohydramnios in postterm pregnancy. Obstet Gynecol 100:715-718, 2002 41. Lam H, Leung WC, Lee CP, et al: The use of fetal Doppler cerebroplacental blood flow and amniotic fluid volume measurement in the surveillance of postdated pregnancies. Acta Obstet Gynecol Scand 84:844-848, 2005
300 42. Figueras F, Lanna M, Palacio M, et al: Middle cerebral artery Doppler indices at different sites: prediction of umbilical cord gases in prolonged pregnancies. Ultrasound Obstet Gynecol 24:529-533, 2004 43. Pollack RN, Hauer-Pollack G, Divon MY: Macrosomia in postdates pregnancies: the accuracy of routine ultrasonographic screening. Am J Obstet Gynecol 167:7-11, 1992 44. Chervenak JL, Divon MY, Hirsch J, et al: Macrosomia in the post-date pregnancy: is routine sonography screening indicated. Am J Obstet Gynecol 161:753-756, 1989 45. Pollack RN, Divon MY: Problems in detecting fetal macrosomia. Contemporary Ob/Gyn, October 1991 46. O’Reilly-Green CP, Divon MY: Receiver operating characteristic
M.Y. Divon and N. Feldman-Leidner curves of sonographic estimated fetal weight for prediction macrosomia in prolonged pregnancies. Ultrasound Obstet Gynecol 9:403-408, 1997 47. Rouse DJ, Owen J: Prophylactic cesarean delivery for fetal macrosomia diagnosed by means of ultrasonography—a Faustian bargain? Am J Obstet Gynecol 181:332-338, 1999 48. Rouse DJ, Owen J, Goldenberg RL, et al: The effectiveness and costs of elective cesarean delivery for fetal macrosomia diagnosed by ultrasound. JAMA 276:1480-1486, 1996 49. Crowley P: Interventions for preventing or improving the outcome of delivery at or beyond term. Cochrane Database of Systematic Reviews 2, 2007
Prolonged Pregnancy
T
he standard definition of a prolonged pregnancy is 42 completed weeks of gestation. This definition is endorsed by the American College of Obstetricians and Gynecologists, The World Health Organization, and the International Federation of Gynecology and Obstetrics.1-3 In view of more recent perinatal mortality data that were derived from accurately dated pregnancies, it would be reasonable to conclude that prolonged pregnancy should be defined as gestational age at birth greater than or equal to 41 weeks of gestation. The incidence of prolonged pregnancy varies depending on the criteria used to define gestational age at birth. It is estimated that 4 to 19% of pregnancies reach or exceed 42 weeks gestation and 2 to 7% complete 43 weeks of gestation.
Prolonged Pregnancy as an Indication for Fetal Testing Several studies that have used very large computerized databases of well-dated pregnancies provide insights into the incidence and nature of adverse perinatal outcome in proDepartment of Obstetrics and Gynecology, Lenox Hill Hospital, New York, NY. Address reprint requests to Michael Y. Divon, MD, Department of Obstetrics and Gynecology, Lenox Hill Hospital, 130 E. 77th St., New York, NY 10075. E-mail: [email protected]
0146-0005/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.semperi.2008.04.013
longed pregnancy. Divon and coworkers evaluated fetal and neonatal mortality rates in 181,524 accurately dated term and prolonged pregnancies.4 Their study documented a small but significant increase in fetal mortality in accurately dated pregnancies that extend beyond 41 weeks gestation and demonstrated that fetal growth restriction is independently associated with a large increase in perinatal mortality in these pregnancies. These results were confirmed by other investigators.5,6 Clausson and coworkers documented that perinatal mortality rates in small for gestational age fetuses had higher odds ratio for stillbirth and neonatal death.6 The stillbirth rate did not change significantly when fetuses with congenital malformations were excluded. However, an 80% drop in neonatal deaths occurred when malformed neonates were excluded from the analysis. In addition, prolonged pregnancies were associated with an increased frequency of neonatal convulsions, meconium aspiration syndrome, and Apgar score of ⬍4 at 5 minutes. Again, morbidity in postterm small for gestational age (SGA) infants was higher than in postterm AGA infants. Further support for the concept that the “small and old” fetus suffers from increased perinatal mortality was provided by Campbell and coworkers, who performed a multivariate analysis of factors associated with perinatal death among 65,796 singleton postterm (ⱖ294 days) births.7 Three variables were identified as independent predictors of perinatal mortality. SGA and maternal age equal or greater than 35 years were associated with a significant increase in perinatal mortality. Interestingly, large for gesta295
296 tional age status (ie, birth weight ⱖ90th percentile for gestational age) was associated with a modest protective effect for perinatal death. However, macrosomia was associated with a higher incidence of labor dysfunction, obstetrical trauma, shoulder dystocia, and maternal hemorrhage. Several studies have shown that the incidence of macrosomia increases with advancing gestational between 37 and 43 weeks. In addition, this increase also results in doubling the cesarean rate for protraction or descent disorders.8-10 There is good evidence to suggest that fetal and maternal morbidity are also increased as gestational age advances beyond term. Tunon and coworkers compared neonate intensive care unit (NICU) admission rates among 10,048 term pregnancies and 246 prolonged pregnancies (ⱖ296 days by both scan and last menstrual period (LMP) dates).11 Prolonged pregnancy was associated with a significant increase in NICU admissions (odds ratio, 2.05; 95% CI, 1.35 and 3.12). Several maternal and fetal complications were evaluated in a large (n ⫽ 45,673) retrospective, cohort study by Caughey and Musci.12 The authors concluded “that risks to both mother and infant increase as pregnancy progresses beyond 40 weeks’ gestation, and that antenatal fetal testing should begin sooner than current recommendation of 42 weeks of gestation.” Olesen and coworkers evaluated a large computerized Danish database of singleton, live-born term and postterm (⬎42 weeks) deliveries to quantify maternal and fetal risks associated with postterm delivery.13 Both perinatal and maternal complications were increased significantly in postterm deliveries.
Fetal Surveillance Fetal surveillance may be used in an attempt to observe the prolonged pregnancy safely while awaiting the onset of spontaneous labor. On the one hand, false-positive tests commonly lead to unnecessary interventions that are potentially hazardous to the gravida. On the other hand, to date, no program of fetal testing has been shown to completely eliminate the risk of stillbirth. Data presented earlier in this review indicate that perinatal mortality is significantly increased as early as 41 weeks gestation and possibly even earlier. The optimal gestational age for the initiation of fetal testing has not been established. Jazayeri and coworkers provided physiologic evidence of altered fetal oxygenation in patients at ⱖ41 weeks by demonstrating elevated plasma erythropoietin levels in these patients.14 Thus, it would seem prudent to initiate fetal testing at 41 weeks of gestation. Extensive experience with biophysical profile testing in high-risk populations indicates a perinatal mortality rate of 0.73 per 1000 tested pregnancies within 1 week of a normal test provided that the amniotic fluid volume is normal.15 Twice-weekly testing with the biophysical profile was reported in a series of 307 patients followed beyond 42 weeks of gestation. When the profile score was normal, waiting for
M.Y. Divon and N. Feldman-Leidner spontaneous labor resulted in healthy neonates and a much lower cesarean section rate. No stillbirths were observed in this small series.16 Several investigators have examined the efficacy of using a nonstress test (NST) as a primary testing modality with the addition of sonographic assessment of amniotic fluid. Clark and coworkers tested 279 prolonged pregnancies with this testing scheme. No stillbirths were recorded.17 Miller and coworkers reported on the use of a similar protocol in 6390 prolonged pregnancies.18 The false-negative rate of this test was 0.8 per 1000 women tested—a rate that favorably compares with those reported for the contraction stress test or the complete biophysical profile.15,19 An analysis of all false-positive tests showed that the routine use of nonstress testing combined with the amniotic fluid index (AFI) resulted in a 60% false-positive rate in the prediction of intrapartum fetal compromise compared with a 40% false-positive rate using the complete biophysical profile. This increase in false-positive tests was felt to be partly due to the poor specificity of the AFI in predicting fetal compromise. Alfirevic and Walkinshaw compared the impact on perinatal outcome of two different protocols for antenatal fetal monitoring after 42 weeks.20. One hundred forty-five women with singleton, uncomplicated pregnancies after 42 weeks of gestation were randomly allocated to fetal monitoring by either a biophysical profile combined with computerized cardiotocography or a standard cardiotocography supplemented by measurement of the largest vertical pocket of amniotic fluid. Their results documented significantly more abnormal antenatal monitoring tests in the biophysical profile combined with the computerized cardiotocography group. There were no differences in cord blood gases, neonatal outcome, or outcomes related to labor and delivery between the two groups, but there was a trend toward more obstetric interventions in the biophysical profile combined with the computerized cardiotocography group. Amniotic fluid volume after 42 weeks was more likely to be labeled as abnormal with amniotic fluid index than with largest vertical pocket. Sylvestre and coworkers evaluated the incidence of abnormal testing (NST and AFI) as a function of birth weight in 792 uncomplicated prolonged pregnancies (⬎41 weeks).21 They showed an inverse relationship between abnormal testing and birth weight. In addition, small fetuses were more likely to require a cesarean delivery for non-reassuring fetal status during labor than were all other fetuses. Thus, it is reasonable to conclude that the small, postterm fetus is not only more likely to die in utero but is also more likely to fail antepartum fetal testing and to be delivered by nonelective cesarean section for an intrapartum diagnosis of non-reassuring fetal status. The implicit assumption in the expectant management strategy is that the presence of an abnormal fetal test (such as oligohydramnios, low biophysical profile score, or spontaneous fetal heart rate decelarations) represents a change in fetal status that requires intervention in the from of prompt delivery. A novel view of the regulation of fetal homeostasis during late gestation was offered by Onyeije and Divon.22 These
Postdates and antenatal testing authors studied the incidence of maternal ketonuria (as a reflection of maternal starvation and dehydration) and its association with abnormal fetal surveillance tests. One thousand eight hundred ninety-five patients were managed expectantly with semiweekly fetal testing. Beginning at 41 weeks gestation, clinically detectable ketonuria occurred in 10.9% of patients studied. Patients with ketonuria were at increased risk for abnormal test results, including the presence of oligohydramnios (24 versus 9.3%, P ⬍ 0.0001), nonreactive NST (6.2 versus 2.15%, P ⬍ 0.0001), and the presence of fetal heart rate decelerations (14 versus 9.2%, P ⬍ 0.0039). The authors suggested that reversible maternal ketonuria contributes to the false-positive test results often encountered in fetal testing, and that such patients might benefit from treatment of ketonuria rather than be delivered in response to the abnormal test results. The formation of amniotic fluid is a complex and poorly understood process. Multiple authors have demonstrated that amniotic fluid volume decreases as gestational age advances beyond 32 or 34 weeks gestation. Marks and Divon evaluated the AFI in 511 well-dated prolonged pregnancies.23 Gestational age at the time of the study ranged from 41 weeks to 43 weeks and 6 days. AFI measurements ranged from 1.7 to 24.6 cm, with a mean and standard deviation of 12.4 ⫾ 4.2 cm at 41 weeks. Oligohydramnios (AFI ⬍5.0 cm) was detected in 11.5% of the study population. Longitudinal data were available from 121 patients. These patients demonstrated a mean decrease in AFI of 25% per week. Thus, the authors concluded that the majority of pregnancies at ⱖ41 weeks gestation have a normal volume of amniotic fluid. In the absence of ruptured membranes or fetal urinary tract abnormalities, diminishing levels of amniotic fluid volume may be related to poor placental function.24 Trimmer and coworkers detected diminished urine production in pregnancies of 42 weeks or more with oligohydramnios and suggested that decreased fetal urine production was the result of preexisting oligohydramnios, which limited fetal swallowing of amniotic fluid rather than a decrease in renal perfusion.25 Bar-Hava and coworkers used pulsed-wave Doppler to evaluate resistance index values in the fetal middle cerebral artery, renal, and umbilical arteries in 57 pregnancies at ⱖ41 weeks gestation.26 It was expected that, with hypoxia, impedance in the cerebral circulation might decrease as impedance increased in the renal circulation. Oligohydramnios (AFI ⬍5 cm) was detected in 15 patients. The various resistance index values and the ratios among them were not significantly different in patients with or without oligohydramnios. Interestingly, the mean birth weight in patients with oligohydramnios was significantly lower than the mean birth weight in patients with a normal AFI. The authors concluded that oligohydramnios in these patients is not associated with a noticeable redistribution of blood flow and suggested that the cause of oligohydramnios is probably unrelated to renal perfusion. The fact that oligohydramnios was found more often in the smaller fetuses is intriguing. It suggests that the appearance of oligohydramnios is a pathologic rather than a physiologic
297 process. It may indicate that the pathophysiology of oligohydramnios in prolonged pregnancy is similar to that involved with the formation of oligohydramnios in the growth-restricted fetus, and overall it is consistent with the concept that it is the small and “older” fetus that is more prone to complications arising from asphyxia. Leveno and coworkers used the presence of oligohydramnios to explain the increased incidence of abnormal antepartum and intrapartum fetal heart rate (FHR) abnormalities seen in prolonged pregnancies.27 These authors suggested that prolonged FHR decelerations representing cord compression preceded 75% of cesarean deliveries for fetal jeopardy. The association between reduced amniotic fluid index and variable decelerations is well documented, as suggested by Gabbe and coworkers, and variable FHR decelerations detected in patients with oligohydramnios are probably related to increased umbilical cord compression.28 Both Phelan and coworkers and Divon and coworkers found that the frequency of nonstress tests demonstrating FHR decelerations or bradycardia increased as the ultrasonographic estimates of the amniotic fluid declined.29-31 The use of an amniotic fluid index ⱕ5.0 cm to define oligohydramnios was first suggested by Phelan and coworkers in 1987, as an arbitrary cutoff value based on retrospective studies. Nevertheless, it has since gained popular appeal.29,30 A meta-analysis evaluated the risk of cesarean delivery for fetal distress, 5-minute Apgar score of ⬍7, and umbilical artery pH ⬍7.00 in patients with antepartum or intrapartum AFI ⬍5.0 cm.32 Eighteen reports describing 10,551 patients at various gestational ages were included in the analysis. The overall incidence of oligohydramnios was 15.2%. The authors concluded that an AFI ⱕ5.0 cm is associated with an increased risk of cesarean delivery for fetal distress (relative risk of 2.2; 95% CI, 1.5-3.4) and an Apgar score of ⬍7 at 5 minutes (relative risk of 5.2; 95% CI, 24113). However, no association was demonstrated between oligohydramnios and severe fetal acidosis. A prospective, blinded observational study of the usefulness of ultrasound assessment of amniotic fluid in the prediction of adverse outcome in the prolonged pregnancy was reported by Morris and coworkers.33 The authors demonstrated that AFI ⬍5 cm was significantly associated with adverse perinatal outcome. Despite these associations, the sensitivity of an AFI ⬍5 cm was very low, ranging from 11.5 to 28.6 for major adverse outcome, fetal distress in labor, or admission to the NICU. The authors concluded that “routine use is likely to lead to increased obstetric intervention without improvement in perinatal outcome” and that large clinical trials are necessary to assess the effectiveness of delivery based on sonographically diagnosed oligohydramnios. In a recent study Lam and coworkers evaluated the usefulness of AFI in the fetal surveillance of postdate pregnancies.34 The authors concluded that “although AFI may be used to predict the occurrence of thick meconium stained liquor and the need for intervention for fetal distress in postdate pregnancies, its role on its own is limited.” The presence of sonographically diagnosed oligohydramnios is often used as an indication for delivery of pregnancies
M.Y. Divon and N. Feldman-Leidner
298 that reach term gestation or extend beyond term. One should however realize that up to 50% of patients, who are diagnosed by ultrasound as having oligohydramnios, will have a normal volume of amniotic fluid on artificial rupture of the membranes.35 In addition, there are no large-scale prospective randomized studies documenting the benefits of delivery once oligohydramnios has been diagnosed. In the absence of such studies, it would seem prudent to deliver patients at or beyond 41 weeks gestation who demonstrate oligohydramnios primarily because of the large body of data which documents an association between diminished amniotic fluid volume and adverse perinatal outcome. Doppler velocimetry is often used to identify fetal compromise due to altered fetal circulation. Its role in establishing fetal well-being in prolonged pregnancies is unclear. Several studies have concluded that the use of umbilical artery Doppler velocimetry is not associated with an improvement of the positive-predictive value of fetal testing in prolonged pregnancy.36-39 Zimmermann and coworkers performed a fetal Doppler cross-sectional, prospective study in 153 pregnancies beyond 287 days of gestation (36% were followed beyond 42 weeks of gestation).39 The resistance indices of the umbilical artery and the middle cerebral artery waveforms were studied every 2 days until delivery. All velocities fell within the known 95% confidence intervals for normal term fetuses. Doppler measurements were unable to predict adverse fetal outcomes, such as abnormal fetal heart rate tracings, thick meconium, the need for urgent operative delivery, acidemia at delivery, or neonatal encephalopathy. In contrast, Oz and coworkers studied 147 well-dated, singleton, postterm pregnancies, of which 21 (14.3%) had oligohydramnios.40 The authors assessed the correlation between renal and umbilical artery Doppler velocimetry, and oligohydramnios. They demonstrated that the renal artery resistance index was significantly higher in cases with oligohydramnios. A renal artery Doppler end-diastolic velocity below the mean for gestational age significantly increased the risk of oligohydramnios (relative risk of 1.5 with 95% CI of 1.1-2.0). Their findings support the hypothesis that increased arterial impedance is an important factor in the development of oligohydramnios in prolonged pregnancies. Two other studies support these findings.41,42 Recently, Lam and coworkers in a prospective observational study of 118 uncomplicated postdated pregnancies at 41 weeks evaluated the distribution of fetal cerebro-placental Doppler indices and amniotic fluid volume.41 The correlation with the incidence of passage of thick meconium in labor was analyzed. The middle cerebral artery pulsatility index was found to be significantly better than amniotic fluid volume or umbilical artery pulsatility index in predicting the risk of thick meconium-stained liquor in labor. Figueras and coworkers in a prospective study of prolonged pregnancies evaluated the value of middle cerebral artery Doppler indices obtained from different sampling sites in predicting umbilical cord gases at delivery.42 Fifty-six patients were included in the final analysis. The proximal middle cerebral artery pulsatility index was found to significantly predict umbilical artery pO2 at delivery but did not predict pH.
In conclusion, given the information available at the present time, it is difficult to define the extent to which the use of Doppler velocimetry can improve the positive-predictive value of fetal testing in prolonged pregnancy. Sonographic fetal weight estimates are often obtained as part of fetal testing in prolonged pregnancies. The accurate and timely prediction of macrosomia may well influence delivery management decisions. However, one should note that the accurate estimation of fetal weight must be viewed in its broad clinical context of feto-pelvic disproportion. Thus, the crucial factor is the relationship of the fetal size to the maternal pelvis rather than the common clinical preoccupation with macrosomia alone. Focusing on either one of these factors in isolation represents a conceptual error.43 Traditionally, obstetricians have predicted fetal weight by abdominal palpation or symphysialfundal height measurement. Ultrasound failed to fulfill the expectation for a more accurate method to estimate fetal weight. Both Chervenak and coworkers and Pollack and coworkers documented that a sonographic estimate of fetal weight of ⬎4000 g had low sensitivity and low positivepredictive value and, therefore, the authors concluded that routine sonographic screening for macrosomia in prolonged pregnancies is associated with relatively low accuracy.43-45 In an attempt to improve the accuracy of sonographic estimates of fetal weight, O’Reilly-Green and Divon used receiver operating characteristic curve analysis to identify optimal cutoff values of estimate of fetal weight in the prediction of macrosomia in prolonged pregnancies.46 The authors concluded that cutoff values derived from their analysis resulted in reasonable sensitivities but disappointingly low positive-predictive values. The practical implications of the low predictive value of ultrasonography have been highlighted by Rouse and coworkers. These authors have shown that in nondiabetic pregnancies the level of intervention and the economic costs of prophylactic cesarean delivery for fetal macrosomia diagnosed by mean of ultrasonography would be excessive.47,48 It would seem reasonable that as fetal weight continues to increase with advancing gestational age, delivery of those pregnancies with a potential for macrosomia might prevent some cases of shoulder dystocia and a subsequent brachial plexus injury. However, this intervention could be achieved only by increasing the rate of inductions of labor or by an increased use of cesarean deliveries, both of which would subject the patient to added morbidity or even unnecessary mortality.
Summary Management of the prolonged pregnancy is primarily determined by the interplay of three factors: certainty of gestational dating, the risks associated with expectant management, and the likelihood of spontaneous vaginal delivery following an induction of labor. A Cochrane Database of Systematic Review from 2007 assessed the effects of interventions aimed at either reducing the incidence or
Postdates and antenatal testing improving the outcome of postterm pregnancy. Twentysix trials of variable quality were included.49 The author concluded that routine early pregnancy ultrasound examination and subsequent adjustment of delivery date appear to reduce the incidence of postterm pregnancy. Furthermore, routine induction of labor after 41 weeks gestation appears to reduce perinatal mortality. However, there was not enough evidence to evaluate the effects of antenatal testing on fetal wellbeing.
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299 19. Freeman RK, Anderson G, Dorchester W: A prospective multicenter multi institutional study of antepartum fetal heart rate monitoring. II. Contraction stress test versus non-stress test for primary surveillance. Am J Obstet Gynecol 143:778-781, 1982 20. Alfirevic Z, Walkinshaw SA: A randomized controlled trial of simple compared with complex antenatal fetal monitoring after 42 weeks of gestation. Br J Obstet Gynaecol 102:638-643, 1995 21. Sylvestre G, Fisher M, Westgren M, et al: Non-reassuring fetal status in the prolonged pregnancy: the impact of fetal weight. Ultrasound Obstet Gynecol 18:244-247, 2001 22. Onyeije CI, Divon MY: The impact of maternal ketonuria on fetal test results in the setting of postterm pregnancy. Am J Obstet Gynecol 184:713-718, 2001 23. Marks AD, Divon MY: Longitudinal study of the amniotic fluid index in postdates pregnancy. Obstet Gynecol 79:229-233, 1992 24. Gresham El, Rankin JH, Makowski EL, et al: An evaluation of fetal renal function in chronic sheep preparation. J Clin Invest 51:149156, 1972 25. Trimmer KJ, Leveno KJ, Peters MT, et al: Observation on the cause of oligohydramnios in prolonged pregnancy. Am J Obstet Gynecol 163: 1900-1903, 1990 26. Bar-Hava I, Divon MY, Sardo M, et al: Is oligohydramnios in post-term pregnancy associated with redistribution of fetal blood flow? Am J Obstet Gynecol 173:519-522, 1995 27. Leveno KJ, Quirk JG Jr, Cunningham FG, et al: Prolonged pregnancy observations concerning the causes of fetal distress. Am J Obstet Gynecol 150:465-473, 1984 28. Gabbe SG, Ettinger BB, Freeman RK, et al: Umbilical cord compression associated with amniotomy: laboratory observations. Am J Obstet Gynecol 126:353-355, 1976 29. Phelan JP, Smith CV, Broussard P, et al: Amniotic fluid volume assessment with the four-quadrant technique at 36-42 weeks’ gestation. J Reprod Med 32:540-542, 1987 30. Phelan JP, Ahn MO, Smith CV, et al: Amniotic fluid index measurements during pregnancy. J Reprod Med 32:601-604, 1987 31. Divon MY, Marks AD, Henderson CE: Longitudinal measurement of amniotic fluid index in postterm pregnancies and its association with fetal outcome. Am J Obstet Gynecol 172:142, 1995 32. Chauhan SP, Sanderson M, Hendrix N, et al: Perinatal outcome and amniotic fluid index in the antepartum and intrapartum periods: a meta-analysis. Am J Obstet Gynecol 181:1473-1478, 1999 33. Morris JM, Thompson K, Smithey J, et al: The usefulness of ultrasound assessment of amniotic fluid in predicting adverse outcome in prolonged pregnancy: a prospective blinded observational study. BJOG 110:989-994, 2003 34. Lam H, Leung WC, Lee CP, et al: Amniotic fluid volume at 41 weeks and infant outcome. J Reprod Med 2006 6:484-488, 2006 35. O’Reilly-Green CP, Divon MY: Predictive value of amniotic fluid index for oligohydramnios in patients with prolonged pregnancies. J Matern Fetal Med 5:218-226, 1996 36. Strokes HJ, Roberts RV, Newnham JP: Doppler flow velocity waveform analysis in postdate pregnancies. Aust NZ J Obstet Gynecol 31:27-30, 1991 37. Guidetti DA, Divon MY, Cavalieri RL, et al: Fetal umbilical artery flow velocimetry in postdate pregnancies. Am J Obstet Gynecol 157:15211523, 1987 38. Farmakides G, Schulman H, Ducey J, et al: Uterine and umbilical Doppler velocimetry in post term pregnancy. J Reprod Med 33:259261, 1988 39. Zimmermann P, Albck T, Koskinen J, et al: Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy. Ultrasound Obstet Gynecol 5:189-197, 1995 40. Oz AU, Holub B, Mendilcioglu I, et al: Renal artery Doppler investigation of the etiology of oligohydramnios in postterm pregnancy. Obstet Gynecol 100:715-718, 2002 41. Lam H, Leung WC, Lee CP, et al: The use of fetal Doppler cerebroplacental blood flow and amniotic fluid volume measurement in the surveillance of postdated pregnancies. Acta Obstet Gynecol Scand 84:844-848, 2005
300 42. Figueras F, Lanna M, Palacio M, et al: Middle cerebral artery Doppler indices at different sites: prediction of umbilical cord gases in prolonged pregnancies. Ultrasound Obstet Gynecol 24:529-533, 2004 43. Pollack RN, Hauer-Pollack G, Divon MY: Macrosomia in postdates pregnancies: the accuracy of routine ultrasonographic screening. Am J Obstet Gynecol 167:7-11, 1992 44. Chervenak JL, Divon MY, Hirsch J, et al: Macrosomia in the post-date pregnancy: is routine sonography screening indicated. Am J Obstet Gynecol 161:753-756, 1989 45. Pollack RN, Divon MY: Problems in detecting fetal macrosomia. Contemporary Ob/Gyn, October 1991 46. O’Reilly-Green CP, Divon MY: Receiver operating characteristic
M.Y. Divon and N. Feldman-Leidner curves of sonographic estimated fetal weight for prediction macrosomia in prolonged pregnancies. Ultrasound Obstet Gynecol 9:403-408, 1997 47. Rouse DJ, Owen J: Prophylactic cesarean delivery for fetal macrosomia diagnosed by means of ultrasonography—a Faustian bargain? Am J Obstet Gynecol 181:332-338, 1999 48. Rouse DJ, Owen J, Goldenberg RL, et al: The effectiveness and costs of elective cesarean delivery for fetal macrosomia diagnosed by ultrasound. JAMA 276:1480-1486, 1996 49. Crowley P: Interventions for preventing or improving the outcome of delivery at or beyond term. Cochrane Database of Systematic Reviews 2, 2007