Table 1

Baseline characteristics of children with maternal exposure to metformin, combination treatment, or insulin

CharacteristicsMetformin
(n=3967)
Combination treatment
(n=889)
Insulin
(n=5273)
Standardized difference*
Metformin versus insulinCombination treatment versus insulin
Before
IPTW weighting
After
IPTW weighting†
Before IPTW weightingAfter
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
Female1884 (47.5)431 (48.5)2487 (47.2)
Male2083 (52.5)458 (51.5)2786 (52.8)
Year of birth, n (%)0.5360.0671.0600.117
2004–2008608 (15.3)47 (5.3)1479 (28.1)0.2880.0100.6340.013
2009–20131632 (41.1)337 (37.9)2359 (44.7)0.0910.0240.1360.057
2014–20161727 (43.5)505 (56.8)1435 (27.2)0.3440.0330.6190.048
Child’s region of residency at birth, n (%)§0.4510.0270.3780.114
Helsinki1071 (27.0)272 (30.6)914 (17.4)
Pirkanmaa399 (10.1)167 (18.8)1029 (19.5)
Varsinais-Suomi1068 (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 birth3000 (75.6)597 (67.2)3914 (74.2)
Caesarean section966 (24.4)292 (32.8)1358 (25.8)
Missing1 (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)
−0.111−0.0400.1810.051
Maternal pre-pregnancy BMI, median (IQR)¶**29.7
(25.0–34.7)
34.0
(29.4–38.7)
30.1
(26.1–34.9)
0.1300.0460.9850.135
Maternal parity, n (%)0.1870.0360.0350.024
Nulliparous1711 (43.1)239 (26.9)1482 (28.1)0.2640.0480.0310.030
Parity 1–21849 (46.6)487 (54.8)2879 (54.6)0.1270.0190.0030.009
Parity ≥3406 (10.2)163 (18.3)910 (17.3)0.1770.0360.0320.024
Missing1 (0.0)0 (0.0)2 (0.0)NANANANA
Maternal educational level during pregnancy, n (%)0.1300.0390.0300.062
Higher education1802 (45.4)319 (35.9)1995 (37.8)0.1150.0510.0380.084
High school1562 (39.4)425 (47.8)2450 (46.5)0.1180.0220.0300.041
Missing603 (15.2)145 (16.3)828 (15.7)0.0060.0380.0100.059
Maternal smoking during pregnancy, n (%)0.1230.0430.0630.132
Yes570 (14.4)146 (16.4)948 (18.0)0.0780.0370.0610.128
No3338 (84.1)721 (81.1)4147 (78.6)0.1130.0440.0420.132
Missing59 (1.5)22 (2.5)178 (3.4)0.1000.0250.0510.012
Maternal comorbidities before pregnancy
Pregestational T2DM, n (%)154 (3.9)168 (18.9)130 (2.5)0.0950.0030.5360.017
PCOS, n (%)464 (11.7)42 (4.7)124 (2.4)0.2790.0110.1190.006
Obesity at the beginning of pregnancy, n (%)Not included in propensity score
Yes1897 (47.8)641 (72.1)2614 (49.6)
No2019 (50.9)240 (27.0)2549 (48.3)
Missing51 (1.3)8 (0.9)110 (2.1)
Toxemia in pregnancy, n (%)557 (14.0)204 (22.9)834 (15.8)0.0450.0050.1730.106
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)
0.7130.2210.9150.081
Essential hypertension in pregnancy, n (%)58 (1.5)39 (4.4)71 (1.3)0.0120.0120.1790.045
Gestational hypertension in pregnancy, n (%)293 (7.4)104 (11.7)449 (8.5)0.0400.0110.0930.083
Pre-eclampsia in pregnancy, n (%)155 (3.9)55 (6.2)198 (3.8)0.0070.0280.1040.031
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 treatment2892 (72.9)745 (83.8)5220 (99.0)
Prepregnancy metformin only1074 (27.1)130 (14.6)47 (0.9)
Other1 (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 birth60 (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.