Baseline characteristics of children with maternal exposure to metformin, combination treatment, or insulin
| Characteristics | Metformin (n=3967) | Combination treatment (n=889) | Insulin (n=5273) | Standardized difference* | |||
| Metformin versus insulin | Combination treatment versus insulin | ||||||
| Before IPTW weighting | After IPTW weighting† | Before IPTW weighting | After IPTW weighting† | ||||
| Gestational age at birth (weeks), median (IQR)‡ | 39.4 (38.6–40.3) | 38.9 (38.0–39.6) | 39.1 (38.4–40.0) | Not included in propensity score | |||
| Sex, n (%) | Not included in propensity score | ||||||
| Female | 1884 (47.5) | 431 (48.5) | 2487 (47.2) | ||||
| Male | 2083 (52.5) | 458 (51.5) | 2786 (52.8) | ||||
| Year of birth, n (%) | 0.536 | 0.067 | 1.060 | 0.117 | |||
| 2004–2008 | 608 (15.3) | 47 (5.3) | 1479 (28.1) | 0.288 | 0.010 | 0.634 | 0.013 |
| 2009–2013 | 1632 (41.1) | 337 (37.9) | 2359 (44.7) | 0.091 | 0.024 | 0.136 | 0.057 |
| 2014–2016 | 1727 (43.5) | 505 (56.8) | 1435 (27.2) | 0.344 | 0.033 | 0.619 | 0.048 |
| Child’s region of residency at birth, n (%)§ | 0.451 | 0.027 | 0.378 | 0.114 | |||
| Helsinki | 1071 (27.0) | 272 (30.6) | 914 (17.4) | ||||
| Pirkanmaa | 399 (10.1) | 167 (18.8) | 1029 (19.5) | ||||
| Varsinais-Suomi | 1068 (26.9) | 86 (9.7) | 167 (3.2) | ||||
| Other (18 regions) | 1429 (36.0) | 364 (40.9) | 3163 (60.0) | ||||
| Type of delivery, n (%) | Not included in propensity score | ||||||
| Vaginal birth | 3000 (75.6) | 597 (67.2) | 3914 (74.2) | ||||
| Caesarean section | 966 (24.4) | 292 (32.8) | 1358 (25.8) | ||||
| Missing | 1 (0.0) | 0 (0.0) | 1 (0.0) | ||||
| Maternal age at delivery, median (IQR) | 32.0 (28.0–35.0) | 34.0 (30.0–37.0) | 33.0 (29.0–37.0) | −0.111 | −0.040 | 0.181 | 0.051 |
| Maternal pre-pregnancy BMI, median (IQR)¶** | 29.7 (25.0–34.7) | 34.0 (29.4–38.7) | 30.1 (26.1–34.9) | 0.130 | 0.046 | 0.985 | 0.135 |
| Maternal parity, n (%) | 0.187 | 0.036 | 0.035 | 0.024 | |||
| Nulliparous | 1711 (43.1) | 239 (26.9) | 1482 (28.1) | 0.264 | 0.048 | 0.031 | 0.030 |
| Parity 1–2 | 1849 (46.6) | 487 (54.8) | 2879 (54.6) | 0.127 | 0.019 | 0.003 | 0.009 |
| Parity ≥3 | 406 (10.2) | 163 (18.3) | 910 (17.3) | 0.177 | 0.036 | 0.032 | 0.024 |
| Missing | 1 (0.0) | 0 (0.0) | 2 (0.0) | NA | NA | NA | NA |
| Maternal educational level during pregnancy, n (%) | 0.130 | 0.039 | 0.030 | 0.062 | |||
| Higher education | 1802 (45.4) | 319 (35.9) | 1995 (37.8) | 0.115 | 0.051 | 0.038 | 0.084 |
| High school | 1562 (39.4) | 425 (47.8) | 2450 (46.5) | 0.118 | 0.022 | 0.030 | 0.041 |
| Missing | 603 (15.2) | 145 (16.3) | 828 (15.7) | 0.006 | 0.038 | 0.010 | 0.059 |
| Maternal smoking during pregnancy, n (%) | 0.123 | 0.043 | 0.063 | 0.132 | |||
| Yes | 570 (14.4) | 146 (16.4) | 948 (18.0) | 0.078 | 0.037 | 0.061 | 0.128 |
| No | 3338 (84.1) | 721 (81.1) | 4147 (78.6) | 0.113 | 0.044 | 0.042 | 0.132 |
| Missing | 59 (1.5) | 22 (2.5) | 178 (3.4) | 0.100 | 0.025 | 0.051 | 0.012 |
| Maternal comorbidities before pregnancy | |||||||
| Pregestational T2DM, n (%) | 154 (3.9) | 168 (18.9) | 130 (2.5) | 0.095 | 0.003 | 0.536 | 0.017 |
| PCOS, n (%) | 464 (11.7) | 42 (4.7) | 124 (2.4) | 0.279 | 0.011 | 0.119 | 0.006 |
| Obesity at the beginning of pregnancy, n (%) | Not included in propensity score | ||||||
| Yes | 1897 (47.8) | 641 (72.1) | 2614 (49.6) | ||||
| No | 2019 (50.9) | 240 (27.0) | 2549 (48.3) | ||||
| Missing | 51 (1.3) | 8 (0.9) | 110 (2.1) | ||||
| Toxemia in pregnancy, n (%) | 557 (14.0) | 204 (22.9) | 834 (15.8) | 0.045 | 0.005 | 0.173 | 0.106 |
| GDM, n (%) | 2897 (73.0) | 719 (80.9) | 5134 (97.4) | Not included in propensity score | |||
| Gestational week of maternal gestational diabetes diagnosis, median (IQR)††‡‡ | 24.4 (15.0–27.7) | 16.6 (13.6–23.1) | 25.4 (16.7–29.3) | 0.713 | 0.221 | 0.915 | 0.081 |
| Essential hypertension in pregnancy, n (%) | 58 (1.5) | 39 (4.4) | 71 (1.3) | 0.012 | 0.012 | 0.179 | 0.045 |
| Gestational hypertension in pregnancy, n (%) | 293 (7.4) | 104 (11.7) | 449 (8.5) | 0.040 | 0.011 | 0.093 | 0.083 |
| Pre-eclampsia in pregnancy, n (%) | 155 (3.9) | 55 (6.2) | 198 (3.8) | 0.007 | 0.028 | 0.104 | 0.031 |
| Other characteristics | |||||||
| Dispensation of antidiabetic medications within 3 months before the beginning of pregnancy, n (%)§§ | Not included in propensity score | ||||||
| No pre-pregnancy pharmacological antidiabetic treatment | 2892 (72.9) | 745 (83.8) | 5220 (99.0) | ||||
| Prepregnancy metformin only | 1074 (27.1) | 130 (14.6) | 47 (0.9) | ||||
| Other | 1 (0.0) | 14 (1.6) | 6 (0.1) | ||||
| Gestational week of initiating the pharmacological antidiabetic treatment, median (IQR) | 24.3 (4.1–31.6) | 20.1 (14.0–26.1) | 31.3 (26.4–34.0) | Not included in propensity score | |||
| Persistence of diabetes in the mother after birth | 60 (1.5) | 109 (12.3) | 72 (1.4) | Not included in propensity score | |||
| Dispensed cumulative dose of metformin during pregnancy (DDDs), median (IQR) | 50.0 (25.0–75.0) | 100.0 (50.0–150.0) | 0.0 (0.0–0.0) | Not included in propensity score | |||
*The distributions of the variables used in propensity score weighting were compared between exposure groups (metformin only exposure: yes/no), by means of standardized difference of prevalence (binary variable), standardized difference of mean (continuous variable), or Mahalanobis distance (categorical variables with more than two levels).
†Numbers >0.1 are in bold, meaning the variable was not balanced after IPTW weighting.
‡Information missing for two children in the metformin group (<0.1%) and three in the insulin group (<0.1%).
§The three hospital regions with the largest total number of study subjects are presented; counts from the other 18 regions are pooled.
¶Information missing for 51 children in the metformin group (1.3%), 8 in the combination treatment group (0.9%), and 110 in the insulin group (2.1%).
**BMI was categorized as ≤18.5, 18.6–25.0, 25.1–30.0, and >30.0.
††Gestational week of gestational diabetes diagnosis was categorized as: <12; 12–19; 20–23; 24–26; 27–30; >30; GDM detected, time unknown; and no diagnosis of gestational diabetes diagnosis.
‡‡Information missing for 1135 children in the metformin group (28.6%), 172 in the combination treatment group (19.4%), and 177 in the insulin group (3.4%).
§§Subject counts for two most frequent categories are presented. Counts for other six combinations of prepregnancy use of metformin, insulin, and other antidiabetic medications than metformin and insulin are pooled.
BMI, body mass index; GDM, gestational diabetes mellitus; IPTW, inverse probability of treatment weighting; PCOS, polycystic ovary syndrome; T2DM, type 2 diabetes mellitus.