University of Bristol - Explore Bristol Research. Peer reviewed version. Link to published version (if available): /peds.

Transcription

1 Gustavson, K., Ystrom, E., Stoltenberg, C., Susser, E., Suren, P., Magnus, P.,... Reichborn-Kjennerud, T. (2017). Smoking in pregnancy and child ADHD. Pediatrics, 139(2), [e ]. DOI: /peds Peer reviewed version Link to published version (if available): /peds Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via AAP at Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available:

2 Table 1. Characteristics of family members by maternal smoking status and child ADHD diagnosis. Total sample Mother did not smoke N = 104,846 N = 85,355 Maternal age 24 years or younger years 35 years or older Mother smoked N = 7,930 Mean (SD) or N (%) Mean (SD) or N (%) Mean (SD) or N (%) 12,402 (11.8%) 74,271 (70.8%) 18,173 (17.3%) 8,533 (10.0%) 61,902 (72.5%) 14,920 (17.5%) 1,862 (23.5%) 4,786 (60.4%) 1,282 (16.2%) t ADHD N = 102,262 Mean (SD) or N (%) 11,847 (11.6%) 72,602 (71.0%) 17,813 (17.4%) ADHD N = 2,035 Mean (SD) or N (%) 495 (24.3%) 1,276 (62.7%) 264 (13.0%) Paternal age 24 years or younger years 35 years or older 5,495 (5.3%) 63,823 (61.1%) 35,184 (33.7%) 3,603 (4.2%) 52,648 (61.8%) 28,885 (33.9%) 923 (11.7%) 4,468 (56.8%) 2,479 (31.5%) 5,250 (5.1%) 62,237 (61.0%) 34,469 (33.8%) 223 (11.0%) 1,262 (62.5%) 534 (26.4%) Maternal education University/college High school Less than high school 57,688 (64.1%) 25,135 (27.9%) 7,235 (8.0%) 54,743 (67.6%) 21,166 (26.1%) 5,065 (6.3%) 2,029 (27.0%) 3,462 (46.0%) 2,032 (27.0%) 56,749 (64.5%) 24,310 (27.7%) 6,861 (7.8%) 647 (38.7%) 700 (41.9%) 324 (19.4%) Paternal education University/college High school Less than high school 43,667 (50.6%) 33,088 (38.3%) 9,560 (11.1%) 41,635 (53.5%) 28,733 (36.9%) 7,407 (9.5%) 1,336 (19.0%) 3,734 (53.0%) 1,980 (28.1%) 43,010 (51.0%) 32,152 (38.1%) 9,129 (10.8%) 425 (27.0%) 780 (49.5%) 370 (23.5%) Maternal BMI a) 24.0 (4.3) 24.0 (4.2) 24.5 (4.9) 24.0 (4.3) 25.3 (5.6) Paternal BMI 25.8 (3.4) 25.8 (3.3) 26.0 (3.7) 25.8 (3.3) 26.3 (3.9) Maternal ADHD symptoms (scale 0-4 ) 1.10(0.58) 1.08 (0.57) 1.25 (0.64) 1.09 (0.57) 1.30 (0.71) Paternal ADHD symptoms (scale 0-4 ) 1.37 (0.53) 1.36 (0.53) 1.50 (0.59) 1.37 (0.53) 1.55 (0.62)

3 Table 1. Characteristics of family members by maternal smoking status and child ADHD diagnosis (continued). Alcohol consumption during pregnancy ne < once per month >= once per month 69,579 (87.0%) 8,044 (10.1%) 2,350 (2.9%) 63,978 (87.5%) 7,159 (9.8%) 2,003 (2.7%) 5,420 (81.9%) 859 (13.0%) 336 (5.1%) 67,964 (87.1%) 7,826 (10.0%) 2,281 (2.9%) 1,283 (86.4%) 155 (10.4%) 47 (3.2%) Parity = 0 45,783 (43.7%) 38,184 (44.7%) 3,432 (43.3%) 44,592 (43.6%) 943 (46.3%) Child s gender = boy 53,483 (51.0%) 43,559 (51,1%) 4,031 (50.9%) 51,708 (50.6%) 1,480 (72.7%) Child registered with ADHD diagnosis 2,035 (2.0%) 1,389 (1.6%) 364 (4.6%) Child s age (years) in (2.2) 8.8 (2.1) 9.7 (2.2) 8.9 (2.2) 10.3 (1.9) Birth weight in grams 3,600 (563) 3,612 (558) 3,475 (577) 3,603 (554) 3,569 (640) tes: a) Maternal BMI when she became pregnant

4 Table 2. Associations between smoking during pregnancy and offspring ADHD diagnoses examined with four separate Cox proportional hazard analyses. Crude Adjusted c ). of person-months at observed risk a). of cases Incidence rate b) Hazard S.E. 95% C.I. p Hazard S.E. 95% C.I. p N 1) Maternal smoking 6,956, ,996 1, < < ,499 2) Paternal smoking 5,835,047 1,903,566 1, < < ,256 3) Grandmother smoked when pregnant with mother 4,940,118 1,874, < < ,944 4) Mother smoked in previous pregnancies d) 4,239, , < < ,069 tes: Separate analyses were performed for each of the four smoking variables so that the associations between each of them and offspring ADHD are not controlled for each other. Ref: reference group to which smokers are compared. a) Observation period between January 2008 and December 2014 for participants born in or before January b) Per 100,000 person-months under observed risk. c) Adjusted for the following covariates: Maternal and paternal age, maternal and paternal education, maternal and paternal ADHD symptoms, maternal (pre-pregnancy) and paternal BMI, maternal alcohol consumption during pregnancy, parity, child s birth year, and geographical region. d) Only applicable to women who had been pregnant before.

5 Table 3. The association between maternal smoking and offspring ADHD diagnoses compared to the associations with three negative controls, mutually adjusted for each other. Crude a) Adjusted b) Hazard p-value 95% C.I. Chisquarevalue p-value chi-square test Hazard p-value 95% C.I. Chisquarevalue p-value chi-square test Maternal smoking Paternal smoking Maternal smoking Grandmother s smoking < Maternal smoking Maternal smoking in previous pregnancies tes: a) Maternal smoking and the negative controls mutually adjusted for each other, but not adjusted for covariates b) Maternal smoking and the negative controls mutually adjusted for each other and for the following covariates: Maternal and paternal age, maternal and paternal education, maternal and paternal ADHD symptoms, maternal (prepregnancy) and paternal BMI, maternal alcohol consumption during pregnancy, parity, child s birth year, and geographical region. Chi-square values were obtained from testing three null-hypotheses that the association between maternal smoking and offspring ADHD diagnoses was equal to each of the three other associations (Wald tests). Degrees of freedom = 1 in all tests.

6 Table 4. Results from sibling comparison analyses of the assocaition between maternal smoking during pregnancy and child ADHD-symptoms, with and without imputed missing values on the ADHD-measure. b a) S.E. a) p a) b b) S.E. b) P b) Total sample < <0.001 Within effects: Discordant siblings Between- effects: Maternal effects < <0.001 a) Missing values were imputed on the ADHD-measure, and 530 sibling pairs discordant for maternal smoking were available for analysis,; b) Missing values were not imputed on the ADHD-measure, yielding 72 sibling pairs discordant for maternal smoking available for analysis. All analyses were controlled for parity, maternal age, and child s birth year.