3.1 Status of pregnancy outcomes in women with T1D in China

From over 300 000 pregnant women, 289 women with pregestational T1D with a singleton pregnancy were initially ascertained from the 11 participating centers. Twenty-four were excluded due to elective abortion for nonmedical reasons or missing data. Finally, 265 women were included in the analysis (Figure 1). Twenty-five (25/265, 9.43%) of them had a previous history of adverse pregnancy outcomes. For the background population, we managed to collect data from 10 centers (Supplemental Materials, Table S1). The weighted average age at the end of the pregnancy of these women without T1D was 28.88 years.

Ascertainment of pregnant women with type 1 diabetes whose pregnancies ended during 1 January 2004 and 31 December 2014 in the participating centers. T1D, type 1 diabetes

Table 1 shows the maternal characteristics of the studied women with T1D. The number of pregnant women with T1D increased nearly 7-fold over the 11-year study period. However, no significant differences in maternal characteristics were observed among the three periods of 2004 to 2008, 2008 to 2011, and 2012 to 2014. Less than 60% of the studied women used appropriate insulin treatment (basal-bolus injections and continuous subcutaneous insulin injection), and 39.2% used insulin regimens like multiple injections of premixed insulin. Notably, only 22.64% (60/265) of the studied women had their HbA1c tested during the peri-pregnancy period. Among the patients with HbA1c records available, 61.67% (37/60) achieved the peri-conception HbA1c target (≤7.0%), and 43.33% (26/60) achieved the third trimester HbA1c target (≤6.5%).

TABLE 1. Maternal characteristics of singleton pregnant women with pregestational type 1 diabetes in the participating centers Variable Period 1 2004-2007 Period 2 2008-2011 Period 3 2012-2014 Overall P for trend 2004-2014 Number of pregnant women with T1D 30 82 153 265 NA Primiparas, n (%) 19 (63.33) 46 (56.10) 99 (64.71) 164 (61.88) .426 History of adverse pregnancy outcomes prior to the study period, n (%) 5 (16.67) 6 (7.31) 14 (9.15) 25 (9.43) .362 Age at conception, y (SD)a 27.83 (3.38) 27.85 (4.13) 28.30 (4.03) 28.11 (3.98) .398 Age at diabetes diagnosis, y (SD)a 21.45 (8.31) 22.56 (6.56) 22.58 (6.77) 22.02 (6.89) .514 Duration of diabetes at delivery, y (SD)a 7.16 (7.39) 5.67 (5.41) 6.25 (5.26) 5.61 (5.68) .801 Middle school or higher, n (%) 4 (100) 33 (89.19) 93 (95.88) 130 (94.2) .384 Chronic hypertension, n (%) 0 5 (6.2) 3 (2.0) 8 (3.0) NA Preconception diabetic microvascular complications - - - - - Diabetes nephropathy, n (%) 4 (13.33) 3 (3.66) 10 (6.54) 17 (6.42) .181 Diabetes retinopathy, n (%) 7 (23.33) 10 (12.20) 19 (12.42) 36 (13.58) .254 Mode of insulin treatment - - - - Basal-bolus injections, n (%) 12 (40.0) 36 (43.9) 73 (47.7) 121 (45.7) NA CSII, n (%) 4 (13.3) 11 (13.4) 21 (13.7) 36 (13.6) NA Othersb, n (%) 11 (36.7) 36 (41.5) 59 (38.6) 104 (39.2) NA Unknown, n (%) 3 (10) 1 (1.2) 0 4 (1.50) NA Smoking in pregnancy, n 0 0 0 0 NA Drinking in pregnancy, n 0 0 0 0 NA Preconception/first trimester HbA1c ≤ 7.0%, % ([n/N]) 44.44 (4/9) 75 (15/20) 58.06 (18/31) 61.67 (37/60) .246 HbA1c at delivery ≤ 6.5%, % ([n/N]) 44.44 (4/9) 50 (10/20) 38.71 (12/31) 43.33 (26/60) .184 Note: All the denominators of the percentages were the respective numbers of pregnant women with T1D presented in the first row unless otherwise noted. Abbreviations: CSII, continuous subcutaneous insulin injection; HbA1c, glycosylated hemoglobin; NA, not applicable; T1D, type 1 diabetes. a The trend of these variables was tested with linear regression models, and the trend of other variables was tested with Pearson χ2 test. b Others meant insulin regimens other than basal-bolus injections or CSII, such as multiple premixed insulin injections or a combination of premixed and short-/rapid-acting insulin injections.

Adverse pregnancy outcomes in women with and without T1D are summarized in Table 2. One maternal death (0.38%, 1/265) was observed in women with T1D and 83 (0.03%, 83/318486) in women without T1D. Also, women with T1D had significantly higher rates of pregnancy loss (13.21% vs 2.92%, cRR 5.08 [95% CI, 3.56-7.26]), preeclampsia (17.74% vs 4.20%, cRR 4.94 [95% CI, 3.60-6.77]), and caesarean delivery (70.19% vs 51.15%, cRR 2.25 [95% CI, 1.73-2.93]). Besides, 11.32% (30/265) of women with T1D suffered from the progression of diabetic complication(s) during pregnancy.

TABLE 2. Maternal, neonatal, and fetal adverse pregnancy outcomes of women with type 1 diabetes compared to those of women without type 1 diabetes in the participating centers during 2004 and 2014 Pregnancy outcomes Women with T1D Women without T1D χ2 value P value Crude risk ratio 95% CI Overall number (%) 265 (100) 318 486 (100) NA NA NA NA Maternal death, n (%) 1 (0.38) 83 (0.03) 2.61a .067 14.53 2.11-104.76 All pregnancy loss, n (%) 35 (13.21) 9259 (2.92) 98.80 <.001 5.08 3.56-7.26 In the second trimester, n (%) 20 (7.55) NA NA NA NA NA In the third trimester, n (%) 6 (2.26) NA NA NA NA NA Preeclampsia, n (%) 47 (17.74) 13 330 (4.20) 120.41 <.001 4.94 3.60-6.77 Caesarean delivery, n (%) 186 (70.19) 162 891 (51.15) 38.43 <.001 2.25 1.73-2.93 Progression of diabetic complication(s), n (%) 30 (11.32) NA NA NA NA NA Infants of women with T1D Infants of women without T1D χ2 value P value Crude risk ratio 95% CI Gestational age at birth (wk) 28-36 ≥37 All NA NA NA NA NA Overall number (%) 43 (100) 187 (100) 230 (100) 324 820 (100) NA NA NA NA Neonatal death, n (%) 2 (4.65) 5 (2.67) 13 (5.65) 520 (0.16) 390.59a <.001 37.36 21.21-65.82 Preterm birth, n (%) NA NA 43 (19.13) 27 722 (8.53) 30.38 <.001 2.46 1.77-3.43 Congenital malformation(s), n (%)b 5 (11.63) 14 (7.49) 19 (8.26) 9963 (3.53) 15.04 .001 2.46 1.54-3.93 SGA, n (%)c 0 (0.00) 12 (6.42) 12 (5.31) 34 218 (10.53) 6.54 .012 0.48 0.27-0.85 LGA, n (%)c 9 (23.08) 59 (31.55) 68 (30.09) NA NA NA NA NA Macrosomia, n (%)c 3 (7.69) 33 (17.65) 36 (15.93) 8647 (2.66) 152.90 <.001 6.93 4.85-9.90 Admission to NICU, n (%) 33 (76.74) 64 (34.22) 97 (42.17) 99 258 (30.56) 14.61 <.001 1.66 1.28-2.15 Note: All the denominators of the percentages were the respective overall numbers presented in the first row unless otherwise noted. Abbreviations: LGA, large-for-gestational age; NA, not applicable; NICU, neonatal intensive care unit; SGA, small-for-gestational age; T1D, type 1 diabetes. a The χ2 value was subjected to continuity correction. b Data were not available in Nanjing Drum Tower Hospital. The number of live births of women without T1D was 282 509 excluding Nanjing Drum Tower Hospital. c The birth weight data of four neonates of women with T1D were missing.

Adverse outcomes in infants of the studied population are also shown in Table 2. Compared to those born to women without T1D, infants born to women with T1D had increased rates of neonatal death (5.65% vs 0.16%, cRR 37.36 [95% CI, 21.21-65.82]) and congenital malformation(s) (8.26% vs 3.53%, cRR 2.46 [95% CI, 1.54-3.93]) as well as elevated risk of preterm birth (19.13% vs 3.53%, cRR 2.46 [95% CI, 1.77-3.43]), macrosomia (15.93% vs 2.66%, cRR 6.93 [95% CI, 4.85-9.90]), and admission to NICU (42.17% vs 30.56%, cRR 1.66 [95% CI, 1.28-2.15]).

We divided the studied population of women with T1D into three groups according to the time of their pregnancy outcomes: 2004 to 2007, 2008 to 2011, and 2012 to 2014. The pregnancy outcomes of the three periods are summarized in Table 3. We found that the pregnancy outcomes of women with T1D during these periods were largely similar. We established logistic regression models to determine the association of different time periods with the adverse outcomes, adjusted for potential confounding factors. The results indicate that despite approaches to improve pregnancy health exerted over these periods, time period had no statistically significant association with the incidences of adverse pregnancy outcomes in our studied women with T1D (Table 3, all P > .05).

TABLE 3. Trends in maternal and neonatal outcomes of pregnant women with type 1 diabetes in the retrospective study, 2004 to 2014 All Period 1 2004-2007 Period 2 2008-2011 Period 3 2012-2014 P valuea No. of pregnant women with T1D 265 30 82 153 NA Maternal outcomes Maternal death, n (%) 1 (0.38) 0 (0) 0 (0) 1 (0.65) NA Caesarean delivery, n (%) 186 (70.19) 22 (88.00) 60 (81.08) 104 (78.79) .338 Preeclampsia, n (%) 48 (18.11) 6 (20) 19 (23.17) 23 (15.03) .295 Pregnancy loss, n (%) 34 (12.83) 5 (16.67) 8 (9.76) 21 (13.73) .502 Number of live births 230 25 74 132 N/A Neonatal outcomes Neonatal death, n (%) 7 (3.03) 0 (0) 1 (1.35) 6 (4.55) NA Congenital malformation, n (%) 20 (8.65) 4 (16) 5 (6.76) 11 (8.33) .739 Preterm birth, n (%) 43 (18.61) 5 (20) 15 (20.27) 23 (17.42) .719 Gestational age at delivery, wk (SD) 37.45 (1.76) 37.12 (1.64) 37.36 (1.96) 37.48 (1.75) .352b SGA, n (%) 13 (5.62) 0 (0) 5 (6.94) 8 (6.15) .300 LGA, n (%) 70 (30.3) 8 (32.0) 20 (27.78) 42 (32.31) .953 Macrosomia, n (%) 36 (15.59) 3 (12) 13 (18.06) 20 (15.38) .747 Neonatal hypoglycemia, n (%) 38 (16.45) 4 (16.0) 13 (17.57) 21 (15.91) .995 Neonatal jaundice, n (%) 54 (23.37) 3 (12.0) 22 (29.73) 29 (21.97) .639 Respiratory distress, n (%) 17 (7.35) 2 (8.0) 8 (10.81) 7 (5.3) .415 Neonatal admission to NICU, n (%) 96 (41.56) 10 (40.0) 31 (41.89) 55 (41.67) .411 Note: The denominators of the percentages of maternal outcomes were the respective number of pregnant women with T1D in the first row, and the denominators of the percentages of neonatal outcomes were the respective number of live births. Abbreviations: LGA, large-for-gestational age; NA, not applicable; NICU, neonatal intensive care unit; SGA, small-for-gestational age; T1D, type 1 diabetes. a Logistic regression models were established to determine the association of different periods with the adverse outcomes, using time period as a covariate, adjusted for age at conception, duration of diabetes at conception, preconceptional diabetic complication(s), and education level (middle school or higher). b The test was done by linear regression models, and P for trend was calculated.