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Insulin-requiring diabetes in pregnancy: A randomized trial of active induction of labor and expectant management
Insulin-requiring diabetes in pregnancy: A randomized trial of active induction of labor and expectant management Siri L. Kjos, MD, Olivia A. Henry, MPH, MB, BCh, Martin Montoro, MD, Thomas A. Buchanan, MD, and Jorge H. Mestman, MD
Los Angeles, California OBJECTIVE: Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth. STUDY DESIGN: Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestation who were compliant with care and whose infants were judged appropriate for gestational age were randomly assigned to (1) active induction of labor within 5 days or (2) expectant management. The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery. RESULTS: Expectant management increased the gestational age at delivery by 1 week. Approximately half (49%) of the mothers in the expectant management group required induction of labor for obstetric indications. The cesarean delivery rate was not significantly different in the expectant management group (31%) from the active induction group (25%). The mean birth weight (3672 ± 407 gm) and percentage large for gestational age, as defined by birth weight ~ 90th percentile, of infants in the expectantly managed group (23%) was greater than those in the active induction group (3466 ± 372 gm, p < 0.0001, 10% large for gestational age). This difference persisted after controlling for gestational age and maternal age and body weight (p < 0.01). CONCLUSION: In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes, expectant management of pregnancy after 38 weeks' gestation did not reduce the incidence of cesarean delivery. Moreover, there was an increased prevalence of large-for-gestational-age infants (23% vs 10%) and shoulder dystocia (3% vs 0%). Because of these risks, delivery should be contemplated at 38 weeks and, if not pursued, careful monitoring of fetal growth must be performed. (AM J OBSTET GVNECOL 1993; 169:611-5.)
Key words: Diabetes, labor induction, expectant management The infant of the diabetic mother and the infant of the mother with untreated gestational diabetes are at increased risk of perinatal death. I. 2 Until recently the risk of fetal death in term infants of diabetic mothers prompted elective delivery at 38 completed weeks of gestation, after documentation offetallung maturity. In insulin-requiring diabetic pregnancies, this practice of active induction is thought to have contributed to an increased cesarean delivery rate, which in some studies ranges up to 71%.3. 4 In the Los Angeles CountyUniversity of Southern California Women's Hospital, 45% of women with insulin-requiring gestational diabetes, and non-insulin-dependent diabetes before pregFrom the Department of Obstetrics and Gynecology, University of Southern California School of Medicine. Received for publication November 25, 1992; accepted March 10, 1993. Reprints not available. Copyright © 1993 by Mosby-Year Book, Inc. 0002-9378193 $1.00 + .20 6/1/47141
nancy reqmrmg insulin treatment during pregnancy, and class B insulin-dependent diabetes were delivered by cesarean section in 1987 through 1990. In Ireland a low cesarean section rate of 20% was achieved by allowing all uncomplicated pregnancies of insulin-dependent diabetic mothers to continue through 40 weeks. 5 To assess whether the cesarean delivery rate could be safely reduced by expectant management as opposed to our current practice of active induction of labor at 38 weeks, we conducted a randomized comparison of these two approaches in pregnant women with uncomplicated gestational and class B diabetes who required insulin treatment during pregnancy and who were cared for at the Women's Hospital, Los Angeles County-University of Southern California Medical Center. Method
A randomized clinical trial comparing active induction of labor and expectant management was con611
September 1993 Am J Obstet Gynecol
612 Kjos et al.
ducted between October 1987 and February 1991 among 200 women with insulin-requiring diabetes. Women diagnosed before pregnancy with insulin-dependent diabetes mellitus or non-insulin-dependent diabetes mellitus without vascular complications (class B) or with gestational diabetes (class A2) requiring insulin treatment during pregnancy, and with good metabolic control of blood glucose levels, were eligible for the study. Capillary blood glucose was monitored by patients four times daily: fasting and 2 hours after breakfast, lunch, and dinner. In addition, prelunch and predinner glucose levels were measured tWice weekly. Glucose levels were measured visually (with Chemstrips) by 80% of women; 20% used reflectance meters with memory chips. Preprandial and fasting blood glucose levels S 90 mg/dl and postprandial values S 120 mg/dl were considered indicative of good glucose control. Only women satisfying these criteria for at least 90% of the readings were offered participation in the study. In addition, they had to meet the following criteria: (1) 38 completed weeks' gestation (266 days), (2) good compliance with clinic appointments and home blood glucose monitoring, (3) no abnormalities in the twice weekly antepartum assessment with nons tress testing and amniotic fluid volume measurement performed from 34 weeks onward, (4) singleton gestation and cephalic presentation, (5) clinical and ultrasonographic estimation of fetal weight < 3800 gm at 38 completed weeks with no evidence of intrauterine growth retardation, (6) no other medical or obstetric complications, and (7) a candidate for trial of vaginal delivery (no more than two previous cesarean sections). Women gave written informed consent for participation in the study, which was approved by the Research Committee of the Los Angeles County-University of Southern California Medical Center. These women were randomly allotted to active induction or expectant management of the pregnancy. Two hundred women (100 per group) were recruited, a number sufficient to detect a 30% decrease in cesarean section rate on the basis of a power analysis at 80%. Active induction of labor management. Amniocentesis was performed to assess fetal lung maturity in pregnancies where the gestational age could not be determined with accuracy (i.e., first physical examination after 20 weeks or first ultrasonographic scan after 26 weeks). Induction of labor was scheduled within 5 days for those mothers with (1) accurate estimation of fetal age or (2) with evidence of fetal lung maturity, a lecithin sphingomyelin ratio ~2.0. If fetal lung maturity was not confirmed, amniocentesis was repeated 1 week later, while patients continued twice weekly antepartum surveillance (nons tress test and amniotic fluid volume index) and home insulin therapy. Labor was induced with intravenous oxytocin in accordance with
standard protocol. In women with favorable Bishop scores ( < 4), unscarred uteri, and normal amniotic fluid indexes (> 5.0 cm), up to three applications of vaginal prostaglandin (3 mg) were used for cervical ripening before oxytocin treatment. Expectant management. Expectant management consisted of daily split-dose insulin therapy and home blood glucose monitoring, weekly antenatal clinic visits, and twice-weekly antepartum testing. Induction oflabor was undertaken only if any of the following developed: (1) suspected fetal distress as indicated by decelerations or unreactive nonstress testing or low volume of amniotic fluid, (2) preeclampsia, (3) maternal hyperglycemia exceeding the thresholds stated above or ketonuria, (4) estimated fetal weight ~4200 gm, or (5) 42 weeks' (294 days') gestation. Otherwise spontaneous labor was awaited. Maternal age was determined at delivery. Gestational age was calculated from the first day of the last menstrual period, adjusted if ultrasonographic estimation (before 22 weeks) differed from the menstrual age by ~ 10 days. Birth weight for gestational age was assessed by reference to data published for California. 6 Infants whose birth weights were ~ 90th percentile were classified as large for gestational age (LGA). Mter delivery the infants were fed early, capillary blood glucose was monitored for hypoglycemia, and physical examination was performed by a neonatologist. Statistical analysis. One-way analysis of variance was used to compare differences between the study groups for continuous variables (maternal age, gravidity, parity, gestational age, and birth weight). Additional covariate analysis of birth weight adjusting for maternal weight, gestational age, and maternal age was carried out. Mean values are presented with the 95% confidence intervals given in parentheses. Discrete variables, including cesarean section and induction of labor rates, were assessed by X2 analysis. Results
Study population. During the 3 1/2 years of this study over 3000 women with diabetes were delivered at Women's Hospital, 944 of whom required insulin therapy. Two hundred women were enrolled in the study, 100 in the active induction of labor group and 100 in the expectant management group. The remainder of the 944 women included those not enrolled because they did not meet the strict criteria for inclusion in the study, those in whom gestational diabetes had been recently diagnosed, and those who refused randomization. Of the 200 women enrolled, 187 had class A2 gestational diabetes and 13 had class B, non-insulin-requiring diabetes before pregnancy. Nine of the class B diabetics were in the active induction group and four were in the expectant management group. There was no significant
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Table I. Mean maternal age, gravidity, parity, and gestation at enrollment and delivery in active induction of labor and expectant management groups
Maternal age at delivery (yr) Gravidity Parity Maternal weight at delivery (kg) Gestation at entry Interval to delivery (days) Gestation at delivery (wk)
Active induction (n = 100)
Expectant management (n = 100)
32.1 (30.9-33.2) 4.3 (3.9-4.7) 2.5 (2.2-2.9) 83.7 (80.1-87.4) 38 wk 1 day (38 wk-38 wk 2 days) 6.4 (5.3-11.6) 39 wk (38 wk 6 days-39 wk 2 days)
31.9 (30.8-33.0) 4.1 (3.7-4.5) 2.4 (2.0-2.7) 85.0 (81.3-88.8) 38 wk 2 days (38 wk I day-38 wk 3 days 12.8 (11.6-13.9)* 40 wk (39 wk 6 days-40 wk 2 days)t
Numbers in parentheses are 95% confidence intervals.
*p < 0.0001 tp < 0.05.
Table II. Onset of labor in active induction of labor and expectant management groups
Spontaneous labor Induction of labor Cesarean section without labor
Active induction (n = 100)
Expectant management (n = 100)
22 70 8
44 49
7
difference in mean maternal age at delivery, gravidity, or parity between the two study groups (Table I). The mean gestational age at entry to the study was also similar (Table I). The mean interval from enrollment to delivery was 6 days greater in the expectant management group (p < 0.0001), resulting in a mean I-week gain in gestational age (p < 0.05). Labor. In the active induction group spontaneous labor before the scheduled induction occurred in 22 (22%) of the women. In the expectant management group spontaneous labor occurred in 44 (44%), whereas half (49%) required an indicated induction of labor and seven (7%) had cesarean section performed before labor (Table II). The indications for induction in these 49 patients in the expectant management group were abnormal antepartum testing (19), ruptured membranes without ensuing labor or dilatory labor (8), 42 weeks of gestation (7), poor fetal growth (4), pregnancyinduced hypertension (3), suspected macrosomia (1), and maternal insistence on delivery (7). Eight mothers in the active induction of labor group and seven in the expectant management group underwent cesarean delivery without labor (Table 11). In addition, one mother in the expectant management group presented in spontaneous labor with a transverse fetal lie; cesarean section was performed without allowing labor to proceed. Mode of delivery. In the active induction group 25 (25%) were delivered by cesarean section compared
Table III. Mode of delivery and indications for cesarean delivery in active induction of labor and expectant management groups Active induction (n = 100)
Vaginal delivery Cesarean delivery, operative indication Arrest disorder Failed induction of labor Fetal distress Macrosomia Elective repeat* Malpresentation
Expectant management (n = 100)
75 25
69 31
6 6
12 8
7 1 2 3
(2) (1) (2) (3)
3 (1) 4 (3) 3 (3) 1
N umbers in parentheses are those with cesarean delivery and no labor. There is no significant difference in mode of delivery or indications between the groups. *Mother requested cesarean delivery.
with 31 (31 %) in the expectant management group (p = 0.43). During the study period the overall cesarean delivery rate for the Women's Hospital was 13.5%. The indications for cesarean section in both study groups are shown in Table III. Neither the cesarean section rate nor the indications for cesarean section were significantly different between the study groups. Prior cesarean section. Eleven mothers in the induction of labor group and 20 mothers in the expectant management group had at least one previous cesarean section. Because a previous history of cesarean section may influence subsequent success with vaginal delivery, analysis of the mode of delivery was performed after excluding mothers with a prior cesarean section from both groups. Twenty of 89 (22.5%) mothers in the induction oflabor group and 14 of 80 (17.5%) of those in the expectant management group were delivered by cesarean section; this difference was not significant (p = 0.54). Infant birth weight. The mean birth weight of the expectant management group, 3672 gm (95% confi-
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Table IV. Mean gestational age at delivery, mean infant birth weight, and numbers of infants defined as macrosomic (~4000 gm) or LGA in expectant management and active induction of labor groups Active induction (n = 100)
Gestational age at delivery (wk) Birth weight (gm) :;:,4000 gm :;:,4500 gm LGA*
39 (38 wk 6 days-39 wk 2 days) 3446 (3368-3522) 15
o
10
Expectant management (n = 100)
40 (39 wk 6 days-40 wk 2 days) 3672 (3595-3749) 27 2 23
Significance
p < 0.0001
P = 0.05
P = 0.02
Numbers in parentheses are 95% confidence intervals. *LGA is defined as :;:, 90th percentile. Significant differences are denoted by corresponding p values. dence interval 3595 to 3749) was significantly greater than that of the elective delivery group, 3446 gm (95% confidence interval 3368 to 3522) (Table IV). Birth weight remained significantly different between the two groups after controlling for gestational age, maternal weight, and maternal age (p < 0.01). Macrosomia, whether defined as birth weight ~ 4000 gm (27% vs 15%, P = 0.05) or birth weight ~ 90th percentile for gestational age (23% vs 10%, P = 0.02), was significantly more frequent in the expectant management group compared with the active induction group (Table IV). Only two infants weighed ~ 4500 gm; both were in the expectant group. The difference in birth weight occurred in spite of the mothers in each group having similar mean body weights at delivery, 85.0 kg (95% confidence interval 81.3 to 88.8) in the expectant management group compared with 83.7 kg (95% confidence interval 80.1 to 87.4) in the active induction group (Table I). Infant outcome. Mild shoulder dystocia occurred at delivery of three infants, all in the expectant management group. The birth weights of these infants were 3580, 4060,'and 4520 gm; their 5-minute Apgar scores were ~ 8 and there was no evidence of trauma such as bone fracture or Erb's palsy. There were no perinatal deaths or major congenital anomalies, and no neonates exhibited hypoglycemia that required treatment.
Comment Both pre gestational insulin-dependent diabetes mellitus and gestational diabetes are known to be associated with increased perinatal mortality. I. 2 Early elective delivery was introduced to reduce such deaths. Most American obstetricians and fetal medicine specialists electively deliver at least 70% of mothers with insulindependent diabetes mellitus. 4 Induction of labor after the thirty-eighth week of pregnancy is widely advocated" 7. 8 and is standard practice at our institution for all mothers with insulin-dependent or non-insulin-dependent diabetes mellitus or gestational diabetes who require insulin therapy during pregnancy. The practice of active induction of labor may have
contributed to the high cesarean delivery rate in diabetic women. In the United States the 1986 cesarean section rate was 53% in women with diabetes mellitus and 34% in those with "abnormal glucose tolerance."g The former incidence was approximately double the overall cesarean section rate of24% in the United States for that year. 9 Drury et al. 5 contended that obstetric intervention in diabetic mothers can be minimized by intensive control of diabetes and postponement of delivery until 40 weeks' gestation. By following this protocol they achieved a cesarean section rate of 20%, a rate that was still four times greater than the 4.8% rate among nondiabetic women in Ireland. 10 In this study of a selected group of women with uncomplicated, insulin-requiring diabetes, we failed to reduce the cesarean section rate by expectant management of pregnancy (31 %) compared with active induction of labor (25%). At Los Angeles County-University of Southern California Women's Hospital, women with previous cesarean sections are routinely offered a trial of vaginal delivery. Against this background, it was decided not to exclude such women from the current study. The incidence of cesarean section was not significantly different in the expectant management and induction of labor groups, either when all women were included or when those who had a prior cesarean section were excluded. The high rate of induction of labor in the expectant management group (49%) and of cesarean delivery in both groups may reflect a low threshold for interventions that exists in the management of pregnancies with complications such as diabetes. Additionally, diabetes, both gestational. and non-insulin-dependent diabetes mellitus, occurs more frequently in older mothers, in women with higher parity, and in those with a previous large infant, all of whom are at risk of having bigger babies and hence cesarean sections. Infants of mothers managed expectantly had significantly more infants with larger birth weights and more. LGA infants than those managed by active induction of labor. It is known that birth weight is affected not only by diabetes but also by gestational age and maternal
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weight. II. 12 In spite of correcting for maternal age, maternal weight before delivery, and gestational age at delivery, there was still a surprisingly higher prevalence of LGA infants in the expectant management group compared with the active induction oflabor group. This finding suggests that the rate of growth is greater than among the reference California populationS used in assessing LGA. Other investigators have also identified subgroups of women whose infants show accelerated fetal growth. 13-15 Ogata et al. 15 described 10 fetuses that exhibited "accelerated somatic growth"; these infants weighed more at birth, had more subcutaneous fat, and showed much steeper abdominal circumference growth curves than 13 other infants of diabetic mothers. Landon et al. I4 also found accelerated growth in LGA infants and Bochner et al. 13 demonstrated that such infants were more likely to suffer shoulder dystocia or birth trauma or to be delivered by cesarean section for failure to progress. Prolonging the gestation in diabetic pregnancies appears to be associated with not only an absolute increase in size but also an increase in size corrected for gestational age. In this study of expectant management and active induction of labor, there were few intrapartum or postpartum problems. The three cases of mild shoulder dystocia all occurred in the expectant management group and there were no permanent sequelae. In summary, expectant management of pregnancy in women with insulin-treated gestational diabetes or class B pregestational diabetes failed to decrease the cesarean section rate compared with active induction oflabor. In the expectant management group more cases of shoulder dystocia occurred, and there was a significant increase in LGA infants. In view of the accelerated growth of some infants of diabetic mothers at term, any advantage of expectant management must be weighed against the risk of macrosomia. There appears to be no advantage in delaying delivery in women with insulinrequiring diabetes past 38 to 39 weeks' gestation. If delivery is postponed, careful monitoring of fetal size and growth must be performed.
REFERENCES 1. Pedowitz P, Shlevin EL. Review of management of pregnancy complicated by diabetes and altered carbohydrate metabolism. Obstet Gynecol 1964;23:716-29. 2. O'Sullivan JB, Charles D, Mahan CM, Dandrow RV. Gestational diabetes and perinatal mortality rate. AM J OasTET GYNECOL 193;116:901-4. 3. Barss V. Obstetrical management. In Hare JW, ed. Diabetes complicating pregnancy. The Joslin Clinic method. New York: Alan R. Liss, 1989. 4. Landon MB, Gabbe SG, Sachs SL. Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal-fetal specialists. Obstet Gynecol 1990;75:635-40. 5. Drury 1M, Stronge JM, Foley ME, MacDonald DW. Pregnancy in the diabetic patient: timing and mode of delivery. Obstet Gynecol 1983;62:279-82. 6. Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, Tashiro M. Fetal growth and perinatal mortality in California. Obstet Gynecol 1982;59:624-32. 7. Gabbe SG. The diabetic pregnancy: application of scientific rationale. In: Merkatz IR, Adam PAJ, eds. The diabetic pregnancy: a perinatal perspective. New York: Grune & Stratton, 1979. 8. Freinkel N, Dooley SL, Metzger BE. Care of the pregnant woman with insulin-dependent diabetes mellitus. N Engl J Med 1985;313:96-1Ol. 9. Placek PJ, Taffel SM. Recent patterns in cesarean delivery in the United States. Gynecol Clin North Am 1988;15:60727. 10. O'Driscoli K, Foley M. Correlation of decrease in perinatal mortality and increase in cesarean section rates. Obstet GynecoI1983;61:1-5. 11. Green JR, Schumacher LB, Pawson IG, Partridge JC, Kretchmer N. Influence of maternal body habitus and glucose tolerance on birth weight. Obstet Gynecol 1991; 78:235-9. 12. Jacobson JD, Cousins L. A population-based study of maternal and perinatal outcome in patients with gestational diabetes. AM J OasTET GYNECOL 1989; 161 :981-6. 13. Bochner CJ, Medearis AL, Williams J, Castro L, Hobel CJ, Wade ME. Early third-trimester ultrasound screening in gestational diabetes to determine the risk of macrosomia and labor dystocia at term. AM] OaSTET GYNECOL 1987; 157:703-8. 14. Landon MB, Mintz MC, Gabbe SG. Sonographic evaluation of fetal abdominal growth: predictor of the large-forgestational-age infant in pregnancies complicated by diabetes mellitus. AM J OaSTET GYNECOL 1989; 160: 115-2l. 15. Ogata ES, Sabbagha R, Metzger BE, Phelps RL, Depp R, Freinkel N. Serial ultrasonography to assess evolving fetal macrosomia. JAMA 1980;243:2405-8.
Los Angeles, California OBJECTIVE: Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth. STUDY DESIGN: Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestation who were compliant with care and whose infants were judged appropriate for gestational age were randomly assigned to (1) active induction of labor within 5 days or (2) expectant management. The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery. RESULTS: Expectant management increased the gestational age at delivery by 1 week. Approximately half (49%) of the mothers in the expectant management group required induction of labor for obstetric indications. The cesarean delivery rate was not significantly different in the expectant management group (31%) from the active induction group (25%). The mean birth weight (3672 ± 407 gm) and percentage large for gestational age, as defined by birth weight ~ 90th percentile, of infants in the expectantly managed group (23%) was greater than those in the active induction group (3466 ± 372 gm, p < 0.0001, 10% large for gestational age). This difference persisted after controlling for gestational age and maternal age and body weight (p < 0.01). CONCLUSION: In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes, expectant management of pregnancy after 38 weeks' gestation did not reduce the incidence of cesarean delivery. Moreover, there was an increased prevalence of large-for-gestational-age infants (23% vs 10%) and shoulder dystocia (3% vs 0%). Because of these risks, delivery should be contemplated at 38 weeks and, if not pursued, careful monitoring of fetal growth must be performed. (AM J OBSTET GVNECOL 1993; 169:611-5.)
Key words: Diabetes, labor induction, expectant management The infant of the diabetic mother and the infant of the mother with untreated gestational diabetes are at increased risk of perinatal death. I. 2 Until recently the risk of fetal death in term infants of diabetic mothers prompted elective delivery at 38 completed weeks of gestation, after documentation offetallung maturity. In insulin-requiring diabetic pregnancies, this practice of active induction is thought to have contributed to an increased cesarean delivery rate, which in some studies ranges up to 71%.3. 4 In the Los Angeles CountyUniversity of Southern California Women's Hospital, 45% of women with insulin-requiring gestational diabetes, and non-insulin-dependent diabetes before pregFrom the Department of Obstetrics and Gynecology, University of Southern California School of Medicine. Received for publication November 25, 1992; accepted March 10, 1993. Reprints not available. Copyright © 1993 by Mosby-Year Book, Inc. 0002-9378193 $1.00 + .20 6/1/47141
nancy reqmrmg insulin treatment during pregnancy, and class B insulin-dependent diabetes were delivered by cesarean section in 1987 through 1990. In Ireland a low cesarean section rate of 20% was achieved by allowing all uncomplicated pregnancies of insulin-dependent diabetic mothers to continue through 40 weeks. 5 To assess whether the cesarean delivery rate could be safely reduced by expectant management as opposed to our current practice of active induction of labor at 38 weeks, we conducted a randomized comparison of these two approaches in pregnant women with uncomplicated gestational and class B diabetes who required insulin treatment during pregnancy and who were cared for at the Women's Hospital, Los Angeles County-University of Southern California Medical Center. Method
A randomized clinical trial comparing active induction of labor and expectant management was con611
September 1993 Am J Obstet Gynecol
612 Kjos et al.
ducted between October 1987 and February 1991 among 200 women with insulin-requiring diabetes. Women diagnosed before pregnancy with insulin-dependent diabetes mellitus or non-insulin-dependent diabetes mellitus without vascular complications (class B) or with gestational diabetes (class A2) requiring insulin treatment during pregnancy, and with good metabolic control of blood glucose levels, were eligible for the study. Capillary blood glucose was monitored by patients four times daily: fasting and 2 hours after breakfast, lunch, and dinner. In addition, prelunch and predinner glucose levels were measured tWice weekly. Glucose levels were measured visually (with Chemstrips) by 80% of women; 20% used reflectance meters with memory chips. Preprandial and fasting blood glucose levels S 90 mg/dl and postprandial values S 120 mg/dl were considered indicative of good glucose control. Only women satisfying these criteria for at least 90% of the readings were offered participation in the study. In addition, they had to meet the following criteria: (1) 38 completed weeks' gestation (266 days), (2) good compliance with clinic appointments and home blood glucose monitoring, (3) no abnormalities in the twice weekly antepartum assessment with nons tress testing and amniotic fluid volume measurement performed from 34 weeks onward, (4) singleton gestation and cephalic presentation, (5) clinical and ultrasonographic estimation of fetal weight < 3800 gm at 38 completed weeks with no evidence of intrauterine growth retardation, (6) no other medical or obstetric complications, and (7) a candidate for trial of vaginal delivery (no more than two previous cesarean sections). Women gave written informed consent for participation in the study, which was approved by the Research Committee of the Los Angeles County-University of Southern California Medical Center. These women were randomly allotted to active induction or expectant management of the pregnancy. Two hundred women (100 per group) were recruited, a number sufficient to detect a 30% decrease in cesarean section rate on the basis of a power analysis at 80%. Active induction of labor management. Amniocentesis was performed to assess fetal lung maturity in pregnancies where the gestational age could not be determined with accuracy (i.e., first physical examination after 20 weeks or first ultrasonographic scan after 26 weeks). Induction of labor was scheduled within 5 days for those mothers with (1) accurate estimation of fetal age or (2) with evidence of fetal lung maturity, a lecithin sphingomyelin ratio ~2.0. If fetal lung maturity was not confirmed, amniocentesis was repeated 1 week later, while patients continued twice weekly antepartum surveillance (nons tress test and amniotic fluid volume index) and home insulin therapy. Labor was induced with intravenous oxytocin in accordance with
standard protocol. In women with favorable Bishop scores ( < 4), unscarred uteri, and normal amniotic fluid indexes (> 5.0 cm), up to three applications of vaginal prostaglandin (3 mg) were used for cervical ripening before oxytocin treatment. Expectant management. Expectant management consisted of daily split-dose insulin therapy and home blood glucose monitoring, weekly antenatal clinic visits, and twice-weekly antepartum testing. Induction oflabor was undertaken only if any of the following developed: (1) suspected fetal distress as indicated by decelerations or unreactive nonstress testing or low volume of amniotic fluid, (2) preeclampsia, (3) maternal hyperglycemia exceeding the thresholds stated above or ketonuria, (4) estimated fetal weight ~4200 gm, or (5) 42 weeks' (294 days') gestation. Otherwise spontaneous labor was awaited. Maternal age was determined at delivery. Gestational age was calculated from the first day of the last menstrual period, adjusted if ultrasonographic estimation (before 22 weeks) differed from the menstrual age by ~ 10 days. Birth weight for gestational age was assessed by reference to data published for California. 6 Infants whose birth weights were ~ 90th percentile were classified as large for gestational age (LGA). Mter delivery the infants were fed early, capillary blood glucose was monitored for hypoglycemia, and physical examination was performed by a neonatologist. Statistical analysis. One-way analysis of variance was used to compare differences between the study groups for continuous variables (maternal age, gravidity, parity, gestational age, and birth weight). Additional covariate analysis of birth weight adjusting for maternal weight, gestational age, and maternal age was carried out. Mean values are presented with the 95% confidence intervals given in parentheses. Discrete variables, including cesarean section and induction of labor rates, were assessed by X2 analysis. Results
Study population. During the 3 1/2 years of this study over 3000 women with diabetes were delivered at Women's Hospital, 944 of whom required insulin therapy. Two hundred women were enrolled in the study, 100 in the active induction of labor group and 100 in the expectant management group. The remainder of the 944 women included those not enrolled because they did not meet the strict criteria for inclusion in the study, those in whom gestational diabetes had been recently diagnosed, and those who refused randomization. Of the 200 women enrolled, 187 had class A2 gestational diabetes and 13 had class B, non-insulin-requiring diabetes before pregnancy. Nine of the class B diabetics were in the active induction group and four were in the expectant management group. There was no significant
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Table I. Mean maternal age, gravidity, parity, and gestation at enrollment and delivery in active induction of labor and expectant management groups
Maternal age at delivery (yr) Gravidity Parity Maternal weight at delivery (kg) Gestation at entry Interval to delivery (days) Gestation at delivery (wk)
Active induction (n = 100)
Expectant management (n = 100)
32.1 (30.9-33.2) 4.3 (3.9-4.7) 2.5 (2.2-2.9) 83.7 (80.1-87.4) 38 wk 1 day (38 wk-38 wk 2 days) 6.4 (5.3-11.6) 39 wk (38 wk 6 days-39 wk 2 days)
31.9 (30.8-33.0) 4.1 (3.7-4.5) 2.4 (2.0-2.7) 85.0 (81.3-88.8) 38 wk 2 days (38 wk I day-38 wk 3 days 12.8 (11.6-13.9)* 40 wk (39 wk 6 days-40 wk 2 days)t
Numbers in parentheses are 95% confidence intervals.
*p < 0.0001 tp < 0.05.
Table II. Onset of labor in active induction of labor and expectant management groups
Spontaneous labor Induction of labor Cesarean section without labor
Active induction (n = 100)
Expectant management (n = 100)
22 70 8
44 49
7
difference in mean maternal age at delivery, gravidity, or parity between the two study groups (Table I). The mean gestational age at entry to the study was also similar (Table I). The mean interval from enrollment to delivery was 6 days greater in the expectant management group (p < 0.0001), resulting in a mean I-week gain in gestational age (p < 0.05). Labor. In the active induction group spontaneous labor before the scheduled induction occurred in 22 (22%) of the women. In the expectant management group spontaneous labor occurred in 44 (44%), whereas half (49%) required an indicated induction of labor and seven (7%) had cesarean section performed before labor (Table II). The indications for induction in these 49 patients in the expectant management group were abnormal antepartum testing (19), ruptured membranes without ensuing labor or dilatory labor (8), 42 weeks of gestation (7), poor fetal growth (4), pregnancyinduced hypertension (3), suspected macrosomia (1), and maternal insistence on delivery (7). Eight mothers in the active induction of labor group and seven in the expectant management group underwent cesarean delivery without labor (Table 11). In addition, one mother in the expectant management group presented in spontaneous labor with a transverse fetal lie; cesarean section was performed without allowing labor to proceed. Mode of delivery. In the active induction group 25 (25%) were delivered by cesarean section compared
Table III. Mode of delivery and indications for cesarean delivery in active induction of labor and expectant management groups Active induction (n = 100)
Vaginal delivery Cesarean delivery, operative indication Arrest disorder Failed induction of labor Fetal distress Macrosomia Elective repeat* Malpresentation
Expectant management (n = 100)
75 25
69 31
6 6
12 8
7 1 2 3
(2) (1) (2) (3)
3 (1) 4 (3) 3 (3) 1
N umbers in parentheses are those with cesarean delivery and no labor. There is no significant difference in mode of delivery or indications between the groups. *Mother requested cesarean delivery.
with 31 (31 %) in the expectant management group (p = 0.43). During the study period the overall cesarean delivery rate for the Women's Hospital was 13.5%. The indications for cesarean section in both study groups are shown in Table III. Neither the cesarean section rate nor the indications for cesarean section were significantly different between the study groups. Prior cesarean section. Eleven mothers in the induction of labor group and 20 mothers in the expectant management group had at least one previous cesarean section. Because a previous history of cesarean section may influence subsequent success with vaginal delivery, analysis of the mode of delivery was performed after excluding mothers with a prior cesarean section from both groups. Twenty of 89 (22.5%) mothers in the induction oflabor group and 14 of 80 (17.5%) of those in the expectant management group were delivered by cesarean section; this difference was not significant (p = 0.54). Infant birth weight. The mean birth weight of the expectant management group, 3672 gm (95% confi-
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Table IV. Mean gestational age at delivery, mean infant birth weight, and numbers of infants defined as macrosomic (~4000 gm) or LGA in expectant management and active induction of labor groups Active induction (n = 100)
Gestational age at delivery (wk) Birth weight (gm) :;:,4000 gm :;:,4500 gm LGA*
39 (38 wk 6 days-39 wk 2 days) 3446 (3368-3522) 15
o
10
Expectant management (n = 100)
40 (39 wk 6 days-40 wk 2 days) 3672 (3595-3749) 27 2 23
Significance
p < 0.0001
P = 0.05
P = 0.02
Numbers in parentheses are 95% confidence intervals. *LGA is defined as :;:, 90th percentile. Significant differences are denoted by corresponding p values. dence interval 3595 to 3749) was significantly greater than that of the elective delivery group, 3446 gm (95% confidence interval 3368 to 3522) (Table IV). Birth weight remained significantly different between the two groups after controlling for gestational age, maternal weight, and maternal age (p < 0.01). Macrosomia, whether defined as birth weight ~ 4000 gm (27% vs 15%, P = 0.05) or birth weight ~ 90th percentile for gestational age (23% vs 10%, P = 0.02), was significantly more frequent in the expectant management group compared with the active induction group (Table IV). Only two infants weighed ~ 4500 gm; both were in the expectant group. The difference in birth weight occurred in spite of the mothers in each group having similar mean body weights at delivery, 85.0 kg (95% confidence interval 81.3 to 88.8) in the expectant management group compared with 83.7 kg (95% confidence interval 80.1 to 87.4) in the active induction group (Table I). Infant outcome. Mild shoulder dystocia occurred at delivery of three infants, all in the expectant management group. The birth weights of these infants were 3580, 4060,'and 4520 gm; their 5-minute Apgar scores were ~ 8 and there was no evidence of trauma such as bone fracture or Erb's palsy. There were no perinatal deaths or major congenital anomalies, and no neonates exhibited hypoglycemia that required treatment.
Comment Both pre gestational insulin-dependent diabetes mellitus and gestational diabetes are known to be associated with increased perinatal mortality. I. 2 Early elective delivery was introduced to reduce such deaths. Most American obstetricians and fetal medicine specialists electively deliver at least 70% of mothers with insulindependent diabetes mellitus. 4 Induction of labor after the thirty-eighth week of pregnancy is widely advocated" 7. 8 and is standard practice at our institution for all mothers with insulin-dependent or non-insulin-dependent diabetes mellitus or gestational diabetes who require insulin therapy during pregnancy. The practice of active induction of labor may have
contributed to the high cesarean delivery rate in diabetic women. In the United States the 1986 cesarean section rate was 53% in women with diabetes mellitus and 34% in those with "abnormal glucose tolerance."g The former incidence was approximately double the overall cesarean section rate of24% in the United States for that year. 9 Drury et al. 5 contended that obstetric intervention in diabetic mothers can be minimized by intensive control of diabetes and postponement of delivery until 40 weeks' gestation. By following this protocol they achieved a cesarean section rate of 20%, a rate that was still four times greater than the 4.8% rate among nondiabetic women in Ireland. 10 In this study of a selected group of women with uncomplicated, insulin-requiring diabetes, we failed to reduce the cesarean section rate by expectant management of pregnancy (31 %) compared with active induction of labor (25%). At Los Angeles County-University of Southern California Women's Hospital, women with previous cesarean sections are routinely offered a trial of vaginal delivery. Against this background, it was decided not to exclude such women from the current study. The incidence of cesarean section was not significantly different in the expectant management and induction of labor groups, either when all women were included or when those who had a prior cesarean section were excluded. The high rate of induction of labor in the expectant management group (49%) and of cesarean delivery in both groups may reflect a low threshold for interventions that exists in the management of pregnancies with complications such as diabetes. Additionally, diabetes, both gestational. and non-insulin-dependent diabetes mellitus, occurs more frequently in older mothers, in women with higher parity, and in those with a previous large infant, all of whom are at risk of having bigger babies and hence cesarean sections. Infants of mothers managed expectantly had significantly more infants with larger birth weights and more. LGA infants than those managed by active induction of labor. It is known that birth weight is affected not only by diabetes but also by gestational age and maternal
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weight. II. 12 In spite of correcting for maternal age, maternal weight before delivery, and gestational age at delivery, there was still a surprisingly higher prevalence of LGA infants in the expectant management group compared with the active induction oflabor group. This finding suggests that the rate of growth is greater than among the reference California populationS used in assessing LGA. Other investigators have also identified subgroups of women whose infants show accelerated fetal growth. 13-15 Ogata et al. 15 described 10 fetuses that exhibited "accelerated somatic growth"; these infants weighed more at birth, had more subcutaneous fat, and showed much steeper abdominal circumference growth curves than 13 other infants of diabetic mothers. Landon et al. I4 also found accelerated growth in LGA infants and Bochner et al. 13 demonstrated that such infants were more likely to suffer shoulder dystocia or birth trauma or to be delivered by cesarean section for failure to progress. Prolonging the gestation in diabetic pregnancies appears to be associated with not only an absolute increase in size but also an increase in size corrected for gestational age. In this study of expectant management and active induction of labor, there were few intrapartum or postpartum problems. The three cases of mild shoulder dystocia all occurred in the expectant management group and there were no permanent sequelae. In summary, expectant management of pregnancy in women with insulin-treated gestational diabetes or class B pregestational diabetes failed to decrease the cesarean section rate compared with active induction oflabor. In the expectant management group more cases of shoulder dystocia occurred, and there was a significant increase in LGA infants. In view of the accelerated growth of some infants of diabetic mothers at term, any advantage of expectant management must be weighed against the risk of macrosomia. There appears to be no advantage in delaying delivery in women with insulinrequiring diabetes past 38 to 39 weeks' gestation. If delivery is postponed, careful monitoring of fetal size and growth must be performed.
REFERENCES 1. Pedowitz P, Shlevin EL. Review of management of pregnancy complicated by diabetes and altered carbohydrate metabolism. Obstet Gynecol 1964;23:716-29. 2. O'Sullivan JB, Charles D, Mahan CM, Dandrow RV. Gestational diabetes and perinatal mortality rate. AM J OasTET GYNECOL 193;116:901-4. 3. Barss V. Obstetrical management. In Hare JW, ed. Diabetes complicating pregnancy. The Joslin Clinic method. New York: Alan R. Liss, 1989. 4. Landon MB, Gabbe SG, Sachs SL. Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal-fetal specialists. Obstet Gynecol 1990;75:635-40. 5. Drury 1M, Stronge JM, Foley ME, MacDonald DW. Pregnancy in the diabetic patient: timing and mode of delivery. Obstet Gynecol 1983;62:279-82. 6. Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, Tashiro M. Fetal growth and perinatal mortality in California. Obstet Gynecol 1982;59:624-32. 7. Gabbe SG. The diabetic pregnancy: application of scientific rationale. In: Merkatz IR, Adam PAJ, eds. The diabetic pregnancy: a perinatal perspective. New York: Grune & Stratton, 1979. 8. Freinkel N, Dooley SL, Metzger BE. Care of the pregnant woman with insulin-dependent diabetes mellitus. N Engl J Med 1985;313:96-1Ol. 9. Placek PJ, Taffel SM. Recent patterns in cesarean delivery in the United States. Gynecol Clin North Am 1988;15:60727. 10. O'Driscoli K, Foley M. Correlation of decrease in perinatal mortality and increase in cesarean section rates. Obstet GynecoI1983;61:1-5. 11. Green JR, Schumacher LB, Pawson IG, Partridge JC, Kretchmer N. Influence of maternal body habitus and glucose tolerance on birth weight. Obstet Gynecol 1991; 78:235-9. 12. Jacobson JD, Cousins L. A population-based study of maternal and perinatal outcome in patients with gestational diabetes. AM J OasTET GYNECOL 1989; 161 :981-6. 13. Bochner CJ, Medearis AL, Williams J, Castro L, Hobel CJ, Wade ME. Early third-trimester ultrasound screening in gestational diabetes to determine the risk of macrosomia and labor dystocia at term. AM] OaSTET GYNECOL 1987; 157:703-8. 14. Landon MB, Mintz MC, Gabbe SG. Sonographic evaluation of fetal abdominal growth: predictor of the large-forgestational-age infant in pregnancies complicated by diabetes mellitus. AM J OaSTET GYNECOL 1989; 160: 115-2l. 15. Ogata ES, Sabbagha R, Metzger BE, Phelps RL, Depp R, Freinkel N. Serial ultrasonography to assess evolving fetal macrosomia. JAMA 1980;243:2405-8.