Background
Methods
Study population
Case ascertainment
Exposures: GWG and RGWG in different pregnancy stages
Covariates
Characteristic | RGWG-T2 | RGWG-T3 | ||||
---|---|---|---|---|---|---|
Optimal | Insufficient | Excessive | Optimal | Insufficient | Excessive | |
N | 10,480 | 7647 | 39,695 | 13,526 | 10,163 | 34,133 |
Weight measurements, median (IQR) | ||||||
1st trimester | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) |
2nd trimester | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) |
3rd trimester | 2.0 (1.0, 4.0) | 3.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) |
Gestational week at the first weight measurement, median (IQR) | ||||||
1st trimester | 9.4 (8.1, 10.7) | 9.3 (8.0, 10.6) | 9.1 (7.9, 10.4) | 9.1 (8.0, 10.4) | 9.3 (8.0, 10.6) | 9.1 (8.0, 10.4) |
2nd trimester | 23.1 (20.0, 24.7) | 22.6 (19.6, 24.6) | 23.0 (19.9, 24.6) | 23.0 (19.9, 24.6) | 23.1 (20.0, 24.7) | 22.9 (19.9, 24.6) |
3rd trimester | 30.9 (29.1, 34.6) | 30.6 (29.1, 33.9) | 30.9 (29.1, 34.7) | 30.9 (29.1, 34.9) | 30.9 (29.3, 34.6) | 30.9 (29.1, 34.6) |
Gestational week at the last weight measurement, median (IQR) | ||||||
1st trimester | 9.6 (8.4, 11.0) | 9.4 (8.1, 10.9) | 9.3 (8.0, 10.6) | 9.4 (8.1, 10.7) | 9.4 (8.1, 10.7) | 9.3 (8.1, 10.7) |
2nd trimester | 25.1 (24.0, 26.1) | 24.9 (24.0, 26.0) | 24.9 (24.0, 26.1) | 24.9 (24.0, 26.0) | 25.0 (24.1, 26.3) | 24.9 (24.0, 26.0) |
3rd trimester | 37.1 (36.0, 38.4) | 37.1 (36.0, 38.3) | 37.1 (36.0, 38.3) | 37.1 (36.0, 38.4) | 37.0 (35.9, 38.3) | 37.1 (36.0, 38.3) |
GWG (kg), mean (SD) | 10.8 (2.9) | 7.8 (3.8) | 14.8 (4.2) | 11.6 (3.2) | 8.9 (3.7) | 15.0 (4.5) |
RGWG-T2 (kg/week), mean (SD) | 0.4 (0.1) | 0.2 (0.2) | 0.7 (0.2) | 0.6 (0.2) | 0.5 (0.3) | 0.6 (0.3) |
RGWG-T2, % | ||||||
Optimal | 10,480 (100.0%) | NA | NA | 3155 (23.3%) | 2460 (24.2%) | 4865 (14.3%) |
Insufficient | NA | 7647 (100.0%) | NA | 2046 (15.1%) | 2085 (20.5%) | 3516 (10.3%) |
Excessive | NA | NA | 39,695 (100.0%) | 8325 (61.5%) | 5618 (55.3%) | 25,752 (75.4%) |
RGWG-T3, kg/week, mean (SD) | 0.5 (0.2) | 0.5 (0.3) | 0.5 (0.2) | 0.4 (0.1) | 0.2 (0.2) | 0.7 (0.2) |
RGWG-T3, % | ||||||
Optimal | 3155 (30.1%) | 2046 (26.8%) | 8325 (21.0%) | 13,526 (100.0%) | NA | NA |
Insufficient | 2460 (23.5%) | 2085 (27.3%) | 5618 (14.2%) | NA | 10,163 (100.0%) | NA |
Excessive | 4865 (46.4%) | 3516 (46.0%) | 25,752 (64.9%) | NA | NA | 34,133 (100.0%) |
Child’s sex, % | ||||||
Male | 5256 (50.2%) | 3748 (49.0%) | 20,577 (51.8%) | 6810 (50.3%) | 5043 (49.6%) | 17,728 (51.9%) |
Female | 5224 (49.8%) | 3899 (51.0%) | 19,118 (48.2%) | 6716 (49.7%) | 5120 (50.4%) | 16,405 (48.1%) |
Maternal BMI at the first antenatal visit, % | ||||||
Normal (18.5–25 kg/m2) (optimal range 0.35–0.50 kg/week) | 8478 (80.9%) | 4948 (64.7%) | 25,549 (64.4%) | 11,304 (83.6%) | 7748 (76.2%) | 19,923 (58.4%) |
Underweight (> 18.5 kg/m2) (optimal range 0.44–0.58 kg/week) | 490 (4.7%) | 420 (5.5%) | 855 (2.2%) | 521 (3.9%) | 735 (7.2%) | 509 (1.5%) |
Overweight (25–30 kg/m2) (optimal range 0.23–0.33 kg/week) | 981 (9.4%) | 1212 (15.8%) | 10,071 (25.4%) | 1209 (8.9%) | 1106 (10.9%) | 9949 (29.1%) |
Obese (> 30 kg/m2) (optimal range 0.17– 0.27 kg/week) | 531 (5.1%) | 1067 (14.0%) | 3220 (8.1%) | 492 (3.6%) | 574 (5.6%) | 3752 (11.0%) |
Maternal age at birth (years), % | ||||||
< 25 | 1043 (10.0%) | 973 (12.7%) | 3795 (9.6%) | 1067 (7.9%) | 821 (8.1%) | 3923 (11.5%) |
25–29 | 2657 (25.4%) | 1972 (25.8%) | 9957 (25.1%) | 3105 (23.0%) | 2128 (20.9%) | 9353 (27.4%) |
30–34 | 4010 (38.3%) | 2724 (35.6%) | 15,029 (37.9%) | 5325 (39.4%) | 3858 (38.0%) | 12,580 (36.9%) |
35–39 | 2311 (22.1%) | 1605 (21.0%) | 9098 (22.9%) | 3391 (25.1%) | 2708 (26.6%) | 6915 (20.3%) |
≥ 40 | 459 (4.4%) | 373 (4.9%) | 1816 (4.6%) | 638 (4.7%) | 648 (6.4%) | 1362 (4.0%) |
Maternal smoking during pregnancy, % | ||||||
No | 9940 (94.8%) | 7112 (93.0%) | 37,168 (93.6%) | 12,836 (94.9%) | 9479 (93.3%) | 31,905 (93.5%) |
Yes | 444 (4.2%) | 491 (6.4%) | 2132 (5.4%) | 602 (4.5%) | 608 (6.0%) | 1857 (5.4%) |
Missing | 96 (0.9%) | 44 (0.6%) | 395 (1.0%) | 88 (0.7%) | 76 (0.7%) | 371 (1.1%) |
Maternal birth region, % | ||||||
Nordic | 7985 (76.2%) | 5390 (70.5%) | 29,572 (74.5%) | 10,317 (76.3%) | 7451 (73.3%) | 25,179 (73.8%) |
Europe | 557 (5.3%) | 405 (5.3%) | 2469 (6.2%) | 739 (5.5%) | 556 (5.5%) | 2136 (6.3%) |
Africa | 459 (4.4%) | 609 (8.0%) | 1455 (3.7%) | 544 (4.0%) | 650 (6.4%) | 1329 (3.9%) |
Asia | 1203 (11.5%) | 1009 (13.2%) | 5126 (12.9%) | 1585 (11.7%) | 1278 (12.6%) | 4475 (13.1%) |
Others | 276 (2.6%) | 233 (3.0%) | 1069 (2.7%) | 341 (2.5%) | 228 (2.2%) | 1009 (3.0%) |
Missing | 0 (0.0%) | NA (< 1%) | NA (< 1%) | 0 (0.0%) | 0 (0.0%) | NA (< 1%) |
Paternal birth region, % | ||||||
Nordic | 7928 (75.6%) | 5297 (69.3%) | 28,796 (72.5%) | 10,165 (75.2%) | 7330 (72.1%) | 24,526 (71.9%) |
Europe | 597 (5.7%) | 389 (5.1%) | 2408 (6.1%) | 793 (5.9%) | 541 (5.3%) | 2060 (6.0%) |
Africa | 475 (4.5%) | 621 (8.1%) | 1699 (4.3%) | 580 (4.3%) | 676 (6.7%) | 1539 (4.5%) |
Asia | 1033 (9.9%) | 952 (12.4%) | 5066 (12.8%) | 1475 (10.9%) | 1167 (11.5%) | 4409 (12.9%) |
Others | 325 (3.1%) | 277 (3.6%) | 1288 (3.2%) | 372 (2.8%) | 314 (3.1%) | 1204 (3.5%) |
Missing | 122 (1.2%) | 111 (1.5%) | 438 (1.1%) | 141 (1.0%) | 135 (1.3%) | 395 (1.2%) |
Maternal education level, % | ||||||
Pre-highschool | 954 (9.1%) | 996 (13.0%) | 3947 (9.9%) | 1148 (8.5%) | 1082 (10.6%) | 3667 (10.7%) |
High-school | 3161 (30.2%) | 2578 (33.7%) | 13,413 (33.8%) | 3996 (29.5%) | 3127 (30.8%) | 12,029 (35.2%) |
Post-high school | 6315 (60.3%) | 4012 (52.5%) | 22,163 (55.8%) | 8317 (61.5%) | 5892 (58.0%) | 18,281 (53.6%) |
Missing | 50 (0.5%) | 61 (0.8%) | 172 (0.4%) | 65 (0.5%) | 62 (0.6%) | 156 (0.5%) |
Household income quintiles at birth, % | ||||||
First (lowest) | 831 (7.9%) | 814 (10.6%) | 2920 (7.4%) | 961 (7.1%) | 887 (8.7%) | 2717 (8.0%) |
Second | 1653 (15.8%) | 1494 (19.5%) | 6742 (17.0%) | 2115 (15.6%) | 1790 (17.6%) | 5984 (17.5%) |
Third | 1663 (15.9%) | 1294 (16.9%) | 6676 (16.8%) | 2065 (15.3%) | 1673 (16.5%) | 5895 (17.3%) |
Fourth | 2090 (19.9%) | 1479 (19.3%) | 8314 (20.9%) | 2710 (20.0%) | 1875 (18.4%) | 7298 (21.4%) |
Fifth (highest) | 4235 (40.4%) | 2552 (33.4%) | 14,981 (37.7%) | 5649 (41.8%) | 3926 (38.6%) | 12,193 (35.7%) |
Missing | 8 (0.1%) | 14 (0.2%) | 62 (0.2%) | 26 (0.2%) | 12 (0.1%) | 46 (0.1%) |
Interpregnancy interval (years), % | ||||||
First born | 4857 (46.3%) | 3404 (44.5%) | 18,550 (46.7%) | 5885 (43.5%) | 3987 (39.2%) | 16,939 (49.6%) |
< 1 | 814 (7.8%) | 678 (8.9%) | 2654 (6.7%) | 1033 (7.6%) | 889 (8.7%) | 2224 (6.5%) |
1–2 | 1774 (16.9%) | 1271 (16.6%) | 6024 (15.2%) | 2375 (17.6%) | 1820 (17.9%) | 4874 (14.3%) |
2–5 | 1957 (18.7%) | 1356 (17.7%) | 7475 (18.8%) | 2606 (19.3%) | 2091 (20.6%) | 6091 (17.8%) |
5–10 | 454 (4.3%) | 361 (4.7%) | 2294 (5.8%) | 713 (5.3%) | 646 (6.4%) | 1750 (5.1%) |
> 10 | 116 (1.1%) | 128 (1.7%) | 640 (1.6%) | 213 (1.6%) | 182 (1.8%) | 489 (1.4%) |
Missing | 508 (4.8%) | 449 (5.9%) | 2058 (5.2%) | 701 (5.2%) | 548 (5.4%) | 1766 (5.2%) |
Maternal psychiatric history, % | 1049 (10.0%) | 878 (11.5%) | 4123 (10.4%) | 1303 (9.6%) | 1167 (11.5%) | 3580 (10.5%) |
Hyperemesis gravidarum, % | 86 (0.8%) | 140 (1.8%) | 376 (1.0%) | 122 (0.9%) | 108 (1.1%) | 372 (1.1%) |
Pre-eclampsia, % | 301 (2.9%) | 293 (3.8%) | 1488 (3.8%) | 241 (1.8%) | 188 (1.9%) | 1653 (4.8%) |
Gestational diabetes mellitus, % | 22 (0.2%) | 31 (0.4%) | 127 (0.3%) | 29 (0.2%) | 48 (0.5%) | 103 (0.3%) |
Statistical analysis
Results
Study sample
Total GWG and risk of NDDs
Rates of GWG in the second trimester and risk of NDDs
Extended categorya | RGWG–T2 | RGWG–T3 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
N cases | %b | Model 1c | Model 2d | P-value | N cases | %b | Model 1c | Model 2d | P-valuee | |
Optimal | ||||||||||
Any NDDs | 380 | 3.63 | 1.00 (ref) | 1.00 (ref) | – | 469 | 3.47 | 1.00 (ref) | 1.00 (ref) | – |
Any ASD | 207 | 1.98 | 1.00 (ref) | 1.00 (ref) | – | 253 | 1.87 | 1.00 (ref) | 1.00 (ref) | – |
Any ADHDf | 217 | 2.07 | 1.00 (ref) | 1.00 (ref) | – | 278 | 2.06 | 1.00 (ref) | 1.00 (ref) | – |
Any ID | 42 | 0.40 | 1.00 (ref) | 1.00 (ref) | – | 51 | 0.38 | 1.00 (ref) | 1.00 (ref) | – |
Extremely insufficient | ||||||||||
Any NDDs | 160 | 4.80 | 1.35 (1.12–1.62) | 1.16 (0.96–1.40) | 0.12 | 165 | 3.61 | 1.05 (0.88–1.26) | 0.99 (0.83–1.18) | 0.91 |
Any ASD | 76 | 2.28 | 1.18 (0.90–1.53) | 1.07 (0.82–1.39) | 0.64 | 83 | 1.82 | 0.99 (0.77–1.27) | 0.95 (0.74–1.21) | 0.66 |
Any ADHDf | 110 | 3.30 | 1.62 (1.29–2.04) | 1.35 (1.07–1.70) | 0.01 | 107 | 2.34 | 1.16 (0.92–1.45) | 1.08 (0.86–1.35) | 0.52 |
Any ID | 23 | 0.69 | 1.76 (1.06–2.92) | 1.42 (0.85– 2.39) | 0.18 | 15 | 0.33 | 0.88 (0.49–1.56) | 0.76 (0.43–1.35) | 0.35 |
Insufficient | ||||||||||
Any NDDs | 183 | 4.24 | 1.19 (1.00–1.42) | 1.12 (0.94–1.34) | 0.20 | 178 | 3.18 | 0.91 (0.77–1.09) | 0.89 (0.75–1.06) | 0.18 |
Any ASD | 88 | 2.04 | 1.06 (0.82–1.36) | 1.02 (0.79–1.31) | 0.89 | 91 | 1.63 | 0.87 (0.68–1.10) | 0.85 (0.67–1.08) | 0.17 |
Any ADHDf | 120 | 2.78 | 1.36 (1.09–1.70) | 1.26 (1.01–1.57) | 0.04 | 111 | 1.98 | 0.96 (0.77–1.19) | 0.93 (0.75–1.16) | 0.53 |
Any ID | 19 | 0.44 | 1.12 (0.65–1.92) | 1.02 (0.59–1.75) | 0.96 | 25 | 0.45 | 1.18 (0.73–1.90) | 1.08 (0.67–1.73) | 0.77 |
Excessive | ||||||||||
Any NDDs | 719 | 3.65 | 0.99 (0.87–1.12) | 0.98 (0.86–1.11) | 0.70 | 677 | 3.57 | 1.02 (0.91–1.15) | 0.98 (0.87–1.10) | 0.69 |
Any ASD | 373 | 1.89 | 0.94 (0.79–1.12) | 0.93 (0.78–1.10) | 0.40 | 350 | 1.84 | 0.98 (0.84–1.16) | 0.95 (0.81–1.11) | 0.51 |
Any ADHDf | 420 | 2.13 | 1.01 (0.86–1.19) | 0.99 (0.85–1.17) | 0.95 | 398 | 2.10 | 1.01 (0.87–1.18) | 0.96 (0.82–1.12) | 0.62 |
Any ID | 97 | 0.49 | 1.22 (0.85–1.75) | 1.21 (0.84–1.74) | 0.31 | 90 | 0.47 | 1.26 (0.89–1.77) | 1.19 (0.84–1.67) | 0.33 |
Extremely excessive | ||||||||||
Any NDDs | 763 | 3.81 | 1.03 (0.91–1.16) | 0.97 (0.86–1.10) | 0.65 | 716 | 4.72 | 1.34 (1.19–1.51) | 1.17 (1.04–1.32) | 0.01 |
Any ASD | 375 | 1.87 | 0.93 (0.78–1.10) | 0.89 (0.75–1.05) | 0.16 | 342 | 2.26 | 1.19 (1.01–1.40) | 1.08 (0.91–1.27) | 0.39 |
Any ADHDf | 486 | 2.43 | 1.14 (0.97–1.34) | 1.07 (0.91–1.25) | 0.43 | 459 | 3.03 | 1.46 (1.26–1.69) | 1.23 (1.06–1.43) | 0.01 |
Any ID | 89 | 0.44 | 1.10 (0.76–1.58) | 1.06 (0.73–1.52) | 0.78 | 89 | 0.59 | 1.56 (1.10–2.20) | 1.44 (1.01–2.03) | 0.04 |