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Current status of pregnancy in diabetic women. A comparison of pregnancy in IDDM and NIDDM mothers
Diabetes Research and C
cal Practice, 24 Suppl. (1994) §273-S278
Ahtract Pregnancy in diabetic patients was uncommon before 196G in Japan. it has increased recently and there has been a 3-fooEd increase since 1971. Only 26% of the cases of diabetic pregnancy had IDDM, th of infants decreased from 10.8% in 1971-1975 to 1.1% in X6-1990, bur rhe Fr 5.7-8.2% during this College. The ratio of to the duration of diabetes was longer The prevalence of maternal COmpiiCatiOnS was NIDDM was often detected for the f&t time du of IDDM mothers but in 5.8% of the infants of NIDDM before pregnancy. Keywr&c
Pregnancy; IDD
I. Introduction
In Japan, the first description of pregnancy in diabetic women appeared in the medical literature in 1932. ancies in diabetics gradxThe number of ill rather low before 1960. ally increased but Since 1971, in order to gather nation-wide data on pregnancy in diabetic patients, we have been sending questionmaires every 5 public hospitals with more than 200 beds. number of pregnancies in diabetics about three-fold since 1971. e.q countries [l], the ratio of
in Japan, so the majority of patients have the non-insu care of diabetes in pregnancy. the nation-wide trend obtaine naires, and our own parison of pre patients.
*Corresponding author. 01688227/94/$07.013 0 1994 Hsevier Science Ireland Ltd. AJl rights resewed SSDI 0168-8227(94hXJ.28-N
s274
I! Onuni et al /Diabetes Res Clh hct.
693 and 694 in 1976-1980, to 899 and 906 in
1981-1985, and to 1160 and 1173 in 1986-1990 [2]. Patients with IDDM comprised oniy 26% of pregnant diabetic women. NameIy, about 3/4 of pregnant diabetic patients had NIDDM. The mean age at delivery was 29 years in 1971-1975 and 31 years in 1986-1990, and the mean age at the unset of diabetes was 25 years. In 1971-1975, 324% of patients were treated with insuiin, 5.6% with oral hypogIycemic agents and 25% by diet onIy, while in 1985-1990, 51.2% were treated with insuhn, 0.3% used oraI agents and 14.6% were treated by diet only. Recentiy, insulin was used more frequently to achieve better glycemia control. The perinatai mortality of infants improved remarkably from 10.8% (41/378) in 1971-1975 to 1.1% (13/1166) in 1985-1990. The most recent figure is comparable with those from the best institutions in the world. Major and minor CongenitaI malformations were observed in 5.7%, 6.5%, 8.2% and 6.5%, respectiveIy, in the periods 1971-1975, 1976-1980, 1981-1985 and 1986-1990. Despite the decrease in perinatal mortaiity, there has been no decreasing tendency in the incidence of malformations. This may indi-
24 SqyL (1994) S273-S278
cate that prepregnancy management of diabetes is still insufficient in this country. Between 1985 and 1990, 114 (10.8%) of 1057 pregnant women developed diabetes at 15 years of age or earlier. The type cf their diabetes was IDDM in 74 and NIDDM in 36 cases, and the remaining 4 were unclassified. 3. Comparison of IDDM and NIDDM pregnancy in patients seen at the Diabetes Center, Tokyo Women’s Medical College 3.1. The ratio of IDDM and NIDDM in pqnant women
Fig. 1 shows the number of deliveries from diabetic mothers since 1964. The type of diabetes was judged clinically and by C-peptide assay. Among these pregnant women 71.8% had NIDDM and 28.2 had IDDM. 3.2. Compakon of IDDM and NIDDMpregnancy Table 1 shows the clinical features of pregnant women with IDDM and NIDDM who were treated at our Diabetes Center from 1988 to 1992. During this period, we managed 207 deliver-
Year Fii 1. Chroaobgkal changes of numbersof pregnant diabeticsin the Diabetes center, Tokyo Women’sMedical College from 1964 to 1991.
K Gmoti et al. / Diaktes Res. Clin. &UC!.24 ~~~~1. Table 1 Comparison of I features
M pregnancy treate
No. cases No. deliveries No. infants
Age at diabetes onset (years) Age at delivery (years) Duration of diabetes at delivery (years) befor nay Obesity: 25 Family history of diabetes 1st degree relative 2nd degree reeletive 3rd degree relative Weeks at delivery Caesarean section
59
68 70 17.8 + 7.7 (l-36) 29.2 f 4.6 (22-40) PI.5 * 7.3 (l-35)
31.7 i: 4.6 (X7-42) 5.6 + 5.9 @-24)
XI.7 f I.8 (17.8-25.7) 2/68 (2.9%) 20/59 (33.9%)
23.2 + 4.6 (16.4-38.5) 42/139 (30.2%) 78/127 (61.4%)
5/59 (8.5%) IQ,‘59 (16.9%) S/S9 (8.5%) 38.3 f 2.0 (31.3-41.1) 22/68 (32.4%)
50/1127 (39.4%) 30/127 (23.6%) 35/127 (27.6%)
Data are given as mean f S.D. with range or percentage given in parentheses.
of diabetes was younger in ID
Fig. 2. Comparison of EDDY and N
pregnancy: age at onset of diabetes and duration of diabetes at de
Y. imrnri et at. /Diabetes
S276 Table 2 amparisoa
Res. Ch. Ract. 24 Suppl. W94) S273-S278
of IDDM and NIDDM pregnancy: prevalence of maternal
complications
IDDM
NIDDM
-Diabetic retinopathy Simple r$iaopathy Proliferative retinopathy Photocoagulation
24/68 (35.3%) 7/68 (10.3%) 2/68 (2.9%)
39/139 08.1%) 6/139 (4.3%) 3/139 (2.2%)
-g Pregnaacy Diabetic nephropathy Toxemia ofpregnanq
4/68 (5.9%) 18/68 (26.5%)
2/139 (1.4%) NS 43/139 (30.9%)
NIDDM patients was within the normal range but 30.2% of NIDDM women had a BMI greater than 25.0. In IDDM patients only 2.9% had a BMI greater than 25.0. The frequency of a positive family history for diabetes was much higher in NIDDM than in IDDM patients (Table 1). The mean week of delivery was 38.3 weeks in both IDDM and NIDDM patients. Caesarean section was done in 32% of IDDM and 36% of NIDDM patients. We experienced no perinatal death of infants during this period. The prevalence of maternal complications of diabetes and toxemia of pregnancy is shown in Table 2. Simple retinopathy was observed in 35% of IDDM and 28% of NIDDM patients. Proliferative retinopathy was more frequent in IDDM than in NIDDM patients but the difference was
-___
NS
not significant. Despite the relatively short duration from diagnosis of diabetes to pregnancy, proliferative retinopathy is a big problem in NIDDM [3]. None of these NIDDM pregnant women knew that they had proliferative retinopathy. Due to few clinical diabetic symptoms, their eyes had not been examined before being referred to us. The need for photocoagulation during pregnancy was nearly the same in the IDDM and NIDDM groups. There were no significant differences in diabetic nephropathy and toxemia of pregnancy between IDDM and NIDDM patients. Changes in insulin dosage during pregnancy are shown in Fig. 3. Insulin requirement during pregnancy gradually increased and reached a maximum at 36-38 weeks of gestation in both
U/day r T
‘T,
JIB.1
- DDL.lop
Fig. 3. Comparison of IDDM and NIDDM pregnancy: changes in insulin dosage during pregnancy.
$277
Fig. 4. Comparison of IDD I appropriate for date;
pregnancy: birth weight of iahnr
according to gestaiional weeks.
groups. The maximal dosage in the t
Fig. 5. Comparison of IDQ
and ~~~~
pregnancy: neonatal corn~~~ca~~~~~.
eavy for date;
X Omoti et al. /Diabetes Res. Clin. Pratt. 24 Suppl. (1994) S273-S278
s27a
Table 3 Comparison of major and minor malformations in IDDM and NIDDM pregnancy
No.delivcries No. infants Major malformation
IDDM
NIDDM
68 70
139 139
oj70
8/139 (5.8%) VSD, PDA VSD, PDA Cleft hp. Cleft palate PDA PDA+PS Hypospadias, VSD + ASD Congenital club foot Myxoma cyst” Holoprosencephaiy VSD, Cleft lip, Cleft palate
Minor malformation
l/70 (1.4%)
6/139 (4.3%)
*Prepregnancy management: the remaining cases were seen on the first visit after pregnancy.
tory distress, hyperbilirubinemia, hypocalcemia and polycythemia did not differ between the infants of IDDM and NIDDM mothers. However, the incidence of malformations was greater in the infants of NIDDM patients. The analysis of malformations revealed that none of 70 infants of 68 IDDM mothers had major malformations, whereas 8 of 139 infants of NIDDM women had major malformations (5.8%) (Table 3) [4]. Seven out of 8 diabetic women who delivered infants with congenital major malformations were referred to us after conception and they had received no prepregnancy management for diabetes. Most of the major anomalies were related to the cardiovascular system. The occurrence of malformation was not related to maternal I-IbA,, levels.
4. Comments In western countries diabetic women with pregnancy mostly have IDDM, while about 75% of the cases of pregnant diabetic women in Japan have NIDDM. Clinical features were similar between IDDM and NIDDM pregnancies, but the age at onset was younger and the duration of diabetes was longer in IDDM. IDDM patients were usually under medical supervision before they became pregnant. The higher incidence of malformation in infants of MDDM patients is probably related to the neglect of diabetes control before pregnancy. Major progress in the management of pregnancy in diabetic patients in Japan during the past 20 years has resulted in a dramatic decrease in perinatal mortality but further efforts are needed in order to decrease congenital malformations by better prepregnancy management. References Laokso, M. and Pyorala, K. (1985) Age of onset and type of diabetes. Diabetes Care 8, 114-117. Omori, Y. (1991) Present status of treatment of pregnant diabetic women. In: K. Kosaka and T. Kusuya, (Eds.), Diabetology 1991, Shindan-to-Chiryo-sha, Tokyo, pp. 199-209 [in Japanese]. Omori, Y., Shimizu, M., Minei, S., Sanaka, M., Honda, M. and Hirata, Y. (1991) Diabetic retinopaty in obese NIDDM pregnant women: new problems in the treatment of pregnant women. In: N. Sakamoto, A. Angel and N. Hotta, @is.), New Directions in Research and Clinical Works for Obesity and Diabetes Meilitus. Elsevier, Amsterdam, pp. 367-372. Omori, Y., Shimizu, M., Minei, S., Morita, Y., Testuo, T., Suzuki, N. and Sam&a, M. (1992) Congenital malformations in newborns from diabetic mothers. Congenital Anomalies 32,293-300.
cal Practice, 24 Suppl. (1994) §273-S278
Ahtract Pregnancy in diabetic patients was uncommon before 196G in Japan. it has increased recently and there has been a 3-fooEd increase since 1971. Only 26% of the cases of diabetic pregnancy had IDDM, th of infants decreased from 10.8% in 1971-1975 to 1.1% in X6-1990, bur rhe Fr 5.7-8.2% during this College. The ratio of to the duration of diabetes was longer The prevalence of maternal COmpiiCatiOnS was NIDDM was often detected for the f&t time du of IDDM mothers but in 5.8% of the infants of NIDDM before pregnancy. Keywr&c
Pregnancy; IDD
I. Introduction
In Japan, the first description of pregnancy in diabetic women appeared in the medical literature in 1932. ancies in diabetics gradxThe number of ill rather low before 1960. ally increased but Since 1971, in order to gather nation-wide data on pregnancy in diabetic patients, we have been sending questionmaires every 5 public hospitals with more than 200 beds. number of pregnancies in diabetics about three-fold since 1971. e.q countries [l], the ratio of
in Japan, so the majority of patients have the non-insu care of diabetes in pregnancy. the nation-wide trend obtaine naires, and our own parison of pre patients.
*Corresponding author. 01688227/94/$07.013 0 1994 Hsevier Science Ireland Ltd. AJl rights resewed SSDI 0168-8227(94hXJ.28-N
s274
I! Onuni et al /Diabetes Res Clh hct.
693 and 694 in 1976-1980, to 899 and 906 in
1981-1985, and to 1160 and 1173 in 1986-1990 [2]. Patients with IDDM comprised oniy 26% of pregnant diabetic women. NameIy, about 3/4 of pregnant diabetic patients had NIDDM. The mean age at delivery was 29 years in 1971-1975 and 31 years in 1986-1990, and the mean age at the unset of diabetes was 25 years. In 1971-1975, 324% of patients were treated with insuiin, 5.6% with oral hypogIycemic agents and 25% by diet onIy, while in 1985-1990, 51.2% were treated with insuhn, 0.3% used oraI agents and 14.6% were treated by diet only. Recentiy, insulin was used more frequently to achieve better glycemia control. The perinatai mortality of infants improved remarkably from 10.8% (41/378) in 1971-1975 to 1.1% (13/1166) in 1985-1990. The most recent figure is comparable with those from the best institutions in the world. Major and minor CongenitaI malformations were observed in 5.7%, 6.5%, 8.2% and 6.5%, respectiveIy, in the periods 1971-1975, 1976-1980, 1981-1985 and 1986-1990. Despite the decrease in perinatal mortaiity, there has been no decreasing tendency in the incidence of malformations. This may indi-
24 SqyL (1994) S273-S278
cate that prepregnancy management of diabetes is still insufficient in this country. Between 1985 and 1990, 114 (10.8%) of 1057 pregnant women developed diabetes at 15 years of age or earlier. The type cf their diabetes was IDDM in 74 and NIDDM in 36 cases, and the remaining 4 were unclassified. 3. Comparison of IDDM and NIDDM pregnancy in patients seen at the Diabetes Center, Tokyo Women’s Medical College 3.1. The ratio of IDDM and NIDDM in pqnant women
Fig. 1 shows the number of deliveries from diabetic mothers since 1964. The type of diabetes was judged clinically and by C-peptide assay. Among these pregnant women 71.8% had NIDDM and 28.2 had IDDM. 3.2. Compakon of IDDM and NIDDMpregnancy Table 1 shows the clinical features of pregnant women with IDDM and NIDDM who were treated at our Diabetes Center from 1988 to 1992. During this period, we managed 207 deliver-
Year Fii 1. Chroaobgkal changes of numbersof pregnant diabeticsin the Diabetes center, Tokyo Women’sMedical College from 1964 to 1991.
K Gmoti et al. / Diaktes Res. Clin. &UC!.24 ~~~~1. Table 1 Comparison of I features
M pregnancy treate
No. cases No. deliveries No. infants
Age at diabetes onset (years) Age at delivery (years) Duration of diabetes at delivery (years) befor nay Obesity: 25 Family history of diabetes 1st degree relative 2nd degree reeletive 3rd degree relative Weeks at delivery Caesarean section
59
68 70 17.8 + 7.7 (l-36) 29.2 f 4.6 (22-40) PI.5 * 7.3 (l-35)
31.7 i: 4.6 (X7-42) 5.6 + 5.9 @-24)
XI.7 f I.8 (17.8-25.7) 2/68 (2.9%) 20/59 (33.9%)
23.2 + 4.6 (16.4-38.5) 42/139 (30.2%) 78/127 (61.4%)
5/59 (8.5%) IQ,‘59 (16.9%) S/S9 (8.5%) 38.3 f 2.0 (31.3-41.1) 22/68 (32.4%)
50/1127 (39.4%) 30/127 (23.6%) 35/127 (27.6%)
Data are given as mean f S.D. with range or percentage given in parentheses.
of diabetes was younger in ID
Fig. 2. Comparison of EDDY and N
pregnancy: age at onset of diabetes and duration of diabetes at de
Y. imrnri et at. /Diabetes
S276 Table 2 amparisoa
Res. Ch. Ract. 24 Suppl. W94) S273-S278
of IDDM and NIDDM pregnancy: prevalence of maternal
complications
IDDM
NIDDM
-Diabetic retinopathy Simple r$iaopathy Proliferative retinopathy Photocoagulation
24/68 (35.3%) 7/68 (10.3%) 2/68 (2.9%)
39/139 08.1%) 6/139 (4.3%) 3/139 (2.2%)
-g Pregnaacy Diabetic nephropathy Toxemia ofpregnanq
4/68 (5.9%) 18/68 (26.5%)
2/139 (1.4%) NS 43/139 (30.9%)
NIDDM patients was within the normal range but 30.2% of NIDDM women had a BMI greater than 25.0. In IDDM patients only 2.9% had a BMI greater than 25.0. The frequency of a positive family history for diabetes was much higher in NIDDM than in IDDM patients (Table 1). The mean week of delivery was 38.3 weeks in both IDDM and NIDDM patients. Caesarean section was done in 32% of IDDM and 36% of NIDDM patients. We experienced no perinatal death of infants during this period. The prevalence of maternal complications of diabetes and toxemia of pregnancy is shown in Table 2. Simple retinopathy was observed in 35% of IDDM and 28% of NIDDM patients. Proliferative retinopathy was more frequent in IDDM than in NIDDM patients but the difference was
-___
NS
not significant. Despite the relatively short duration from diagnosis of diabetes to pregnancy, proliferative retinopathy is a big problem in NIDDM [3]. None of these NIDDM pregnant women knew that they had proliferative retinopathy. Due to few clinical diabetic symptoms, their eyes had not been examined before being referred to us. The need for photocoagulation during pregnancy was nearly the same in the IDDM and NIDDM groups. There were no significant differences in diabetic nephropathy and toxemia of pregnancy between IDDM and NIDDM patients. Changes in insulin dosage during pregnancy are shown in Fig. 3. Insulin requirement during pregnancy gradually increased and reached a maximum at 36-38 weeks of gestation in both
U/day r T
‘T,
JIB.1
- DDL.lop
Fig. 3. Comparison of IDDM and NIDDM pregnancy: changes in insulin dosage during pregnancy.
$277
Fig. 4. Comparison of IDD I appropriate for date;
pregnancy: birth weight of iahnr
according to gestaiional weeks.
groups. The maximal dosage in the t
Fig. 5. Comparison of IDQ
and ~~~~
pregnancy: neonatal corn~~~ca~~~~~.
eavy for date;
X Omoti et al. /Diabetes Res. Clin. Pratt. 24 Suppl. (1994) S273-S278
s27a
Table 3 Comparison of major and minor malformations in IDDM and NIDDM pregnancy
No.delivcries No. infants Major malformation
IDDM
NIDDM
68 70
139 139
oj70
8/139 (5.8%) VSD, PDA VSD, PDA Cleft hp. Cleft palate PDA PDA+PS Hypospadias, VSD + ASD Congenital club foot Myxoma cyst” Holoprosencephaiy VSD, Cleft lip, Cleft palate
Minor malformation
l/70 (1.4%)
6/139 (4.3%)
*Prepregnancy management: the remaining cases were seen on the first visit after pregnancy.
tory distress, hyperbilirubinemia, hypocalcemia and polycythemia did not differ between the infants of IDDM and NIDDM mothers. However, the incidence of malformations was greater in the infants of NIDDM patients. The analysis of malformations revealed that none of 70 infants of 68 IDDM mothers had major malformations, whereas 8 of 139 infants of NIDDM women had major malformations (5.8%) (Table 3) [4]. Seven out of 8 diabetic women who delivered infants with congenital major malformations were referred to us after conception and they had received no prepregnancy management for diabetes. Most of the major anomalies were related to the cardiovascular system. The occurrence of malformation was not related to maternal I-IbA,, levels.
4. Comments In western countries diabetic women with pregnancy mostly have IDDM, while about 75% of the cases of pregnant diabetic women in Japan have NIDDM. Clinical features were similar between IDDM and NIDDM pregnancies, but the age at onset was younger and the duration of diabetes was longer in IDDM. IDDM patients were usually under medical supervision before they became pregnant. The higher incidence of malformation in infants of MDDM patients is probably related to the neglect of diabetes control before pregnancy. Major progress in the management of pregnancy in diabetic patients in Japan during the past 20 years has resulted in a dramatic decrease in perinatal mortality but further efforts are needed in order to decrease congenital malformations by better prepregnancy management. References Laokso, M. and Pyorala, K. (1985) Age of onset and type of diabetes. Diabetes Care 8, 114-117. Omori, Y. (1991) Present status of treatment of pregnant diabetic women. In: K. Kosaka and T. Kusuya, (Eds.), Diabetology 1991, Shindan-to-Chiryo-sha, Tokyo, pp. 199-209 [in Japanese]. Omori, Y., Shimizu, M., Minei, S., Sanaka, M., Honda, M. and Hirata, Y. (1991) Diabetic retinopaty in obese NIDDM pregnant women: new problems in the treatment of pregnant women. In: N. Sakamoto, A. Angel and N. Hotta, @is.), New Directions in Research and Clinical Works for Obesity and Diabetes Meilitus. Elsevier, Amsterdam, pp. 367-372. Omori, Y., Shimizu, M., Minei, S., Morita, Y., Testuo, T., Suzuki, N. and Sam&a, M. (1992) Congenital malformations in newborns from diabetic mothers. Congenital Anomalies 32,293-300.