Breastfeeding and Behavioral Development: A Nationwide Longitudinal Survey in Japan Takashi Yorifuji, MD, PhD1, Toshihide Kubo, MD, PhD2, Michiyo Yamakawa, PhD1, Tsuguhiko Kato, PhD3, Sachiko Inoue, MMS4,5, Akiko Tokinobu, MMS1,4, and Hiroyuki Doi, MD, PhD4 Objective To prospectively examine the prolonged effect of breastfeeding on behavioral development. Study design We used a large, nationwide Japanese population-based longitudinal survey that began in 2001. We restricted participants to term singletons with birth weight >2500 g (n = 41 188). Infant feeding practice was queried at age 6-7 months. Responses to survey questions about age-appropriate behaviors at age 2.5 and 5.5 years were used as indicators of behavioral development. We conducted logistic regression analyses, controlling for potential child and parental confounding factors, with formula feeding as the reference group. Results We observed a dose–response relationship between breastfeeding status and an inability to perform ageappropriate behaviors at both ages. With a single exception, all ORs for outcomes for exclusive breastfeeding were smaller than those for partial feeding of various durations. The protective associations did not change after adjustment for an extensive list of confounders or in the sensitivity analyses. Conclusion We observed prolonged protective effects of breastfeeding on developmental behavior skills surveyed at age 2.5 and 5.5 years. Beneficial effects were most likely in children who were breastfed exclusively, but whether a biological ingredient in breast milk or extensive interactions through breastfeeding, or both, is beneficial is unclear. (J Pediatr 2014;164:1019-25).
T
he World Health Organization recommends exclusive breastfeeding for the first 6 months of life,1 based on accumulated evidence of the protective effects of breastfeeding against infectious diseases (eg, gastrointestinal, respiratory).2-4 In addition, potential prolonged effects of breastfeeding on several outcomes (eg, obesity, cognitive function, dental caries) have been investigated, but the findings remain inconclusive, except for a potential benefit on cognitive function.2,5 Compared with a number of studies that examined the potential benefit of prolonged breastfeeding on several major health outcomes,2,5 few studies have investigated the potential benefit on behavioral development that might be expected because of the close contact between mothers and infants during feeding.6 Although several observational studies have suggested some benefits for several behavioral outcomes from the neonatal period to adolescence,7-14 most of these studies had a small sample size. Moreover, as discussed in studies on cognitive function,5,15-17 residual confounding is thought to explain the observed protective effect of breastfeeding on behavioral outcomes.18 Potential confounders include parental educational status, parental socioeconomic status, and variations in parental effort in teaching. Indeed, a large randomized control trial (RCT) in Belarus did not find a protective effect on behavior in the intention-to-treat analysis comparing 2 groups (breastfeeding promotion group and control group), but did identify a benefit in an observational analysis based on 5 categories of breastfeeding duration.18,19 That study indicates an inherent limitation of observational studies (a possibility of residual confounding), however; the different categorization of each method of analysis in the study calls into question the authors’ conclusions. Consequently, in the present study we prospectively examined the prolonged effect of breastfeeding on behavioral development at age 2.5 and 5.5 years using data from a large Japanese nationwide population-based longitudinal survey. We attempted to determine whether dose–response relationships exist between the duration of breastfeeding and behavioral outcomes, and adjusted for an extensive list of potential confounding variables that might induce a biased association.
Methods The Japanese Ministry of Health, Labour, and Welfare (MHLW) has been surveying parents and their newborn babies annually since 2001. This survey, the Longitudinal Survey of Babies in the 21st Century, is described in detail elsewhere.20-22 In brief, when the newborns were 6 months old, baseline questionnaires were sent to all families throughout Japan that had a baby (or babies) born on January 10-17 or July 10-17, 2001. Among the 53 575 questionnaires MHLW RCT
Japanese Ministry of Health, Labour, and Welfare Randomized control trial
From the 1Department of Human Ecology, Okayama University Graduate School of Environmental and Life Science, Okayama, Japan; 2Department of Pediatrics, Okayama Medical Center, National Hospital Organization, Okayama, Japan; 3Department of Public Health and Public Policy, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 4Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; and 5 Department of Child and Adolescent Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan Supported by Health and Labour Sciences Research (H24-Jisedai-Ippan-004). The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.01.012
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that were mailed, 47 015 were completed and returned (response rate, 88%). Every year (at age 18 months, 30 months, 42 months, and so on), follow-up questionnaires were sent to all participants who initially responded. Birth records from Japanese vital statistics are also linked to each child in this survey. Birth records data include length, weight, gestational age, singleton or twin or other multiple birth, sex, parity, and parental age. For the present study, we targeted children with data collected for the third and sixth surveys (at age 2.5 and 5.5 years, respectively). We restricted the study participants to children born after 37 gestational weeks, with a birth weight >2500 g, and singleton births, because of the potential influence of prematurity, intrauterine growth retardation, and multiples on childhood development (Figure; available at www.jpeds.com). This led to the exclusion of 5125 children from each of the 2 surveys. Children with missing information on feeding practices during infancy (n = 702) were excluded as well. At the third survey, 3551 children were lost to follow-up, leaving 37 637 children in the analysis at age 2.5 years. Similarly, at the sixth survey, 7213 children were lost to follow-up, leaving 33 975 children in the analysis at age 5.5 years. Infant Feeding Practice The first survey at age 6 months included questions on infant feeding practices to determine whether the children had been breastfed, only colostrum-fed, or formula-fed.20 The duration (in months) of breastfeeding and formula feeding was then queried. In the present study, we combined the categories of “never breastfed” and “colostrum only” into a category of “formula feeding” because of the small number in the category of “never breastfed” and the short duration of colostrum feeding (ie, approximately 1 week). We created categories of “partial breastfeeding” and “exclusive breastfeeding” using information on breastfeeding and formula feeding. We further divided the category of “partial breastfeeding” based on the duration of breastfeeding (ie, breastfeeding for 1-2 months, 3-5 months, and 6-7 months). Although the first survey was administered at age 6 months, we included a category of up to 7 months depending on the timing of the response. Children in the exclusive breastfeeding category had been breastfed for 6-7 months. Finally, we categorized the feeding practice as formula feeding, partial breastfeeding (ie, breastfeeding for 1-2 months, 3-5 months, or 6-7 months), or exclusive breastfeeding at age 6-7 months. Behavioral Development Outcomes For behavioral development outcomes, we used the survey questions that elicited information on age-appropriate behavior.21 At age 2.5 years, the following questions were asked: (1) “Can your child climb stairs?”; (2) “Can your child compose 2-phrase sentences?”; (3) “Can your child say his or her own name?”; and (4) “Can your child use a spoon to eat?” We did not use the following questions because the behaviors seemed heavily dependent on parenting practices: “Can your child brush their teeth by him/herself?,” “Does your child 1020
Vol. 164, No. 5 wear a diaper during the day?,” and “Can your child put on clothes by himself?” We also did not use the questions “Can your child walk?,” “Can your child run?,” and “Can your child say things that make sense?,” because almost all responses were affirmative (>99%). The MHLW extracted the behavioral questions used in our analyses from the “Maternal and Child Health Handbook” (“Boshi Kenko Techo”). The Handbook is a record of health and child development given to every pregnant mother in Japan in which all information from postnatal visits is recorded prospectively until the child is 6 years old. The dissemination and use of the Handbook is mandated under Japanese law and has been implemented for decades. At age 5.5 years, the following questions were asked: (1) “Can your child listen without fidgeting?”; (2) “Can your child focus on one task?”; (3) “Is your child patient?”; (4) “Can your child express emotions appropriately?”; (5) “Can your child get along with others in a group setting?”; and (6) “Can your child keep promises?” According to the MHLW, these questions were developed for this survey to capture early signs of behavioral and developmental problems. During the past decade, the MHLW has been attempting to track the prevalence of behavioral and developmental problems; however, we could not confirm whether these questions have been externally validated. Statistical Analyses To evaluate the impact of loss to follow-up (Figure), we first compared baseline characteristics among eligible children, children included in the analysis (at both the third and sixth surveys), and children lost to follow-up. We then compared baseline characteristics according to the infant feeding practices among eligible children. We conducted logistic regression analyses to evaluate the relationships between infant feeding practice and behavioral development at age 2.5 and 5.5 years. We first estimated the crude OR and 95% CI for each outcome (model 1). We then estimated the OR and 95% CI for each outcome after controlling for child factors (model 2) and for both child and parental factors (model 3). Throughout the analyses, the formula feeding group served as the reference group. In the analyses, we controlled for potential confounding factors related to the children and parents based on a review5 or previous original studies10,12,13,16,18 that examined the associations between breastfeeding and cognitive functions or behavioral outcomes. In children, these factors included sex (dichotomous), birth weight (continuous), presence of a sibling (dichotomous), and day care attendance (dichotomous, only in the analysis at age 2.5 years). Parental factors included maternal age at delivery (continuous), maternal smoking habits (dichotomous), parental concern or worry regarding raising children (categorical), maternal educational attainment (categorical), and maternal working status (dichotomous). The child’s sex and birth weight and maternal age at delivery were listed in the birth record. The presence of a sibling was obtained from the information on parity (ie, number of deliveries) in the birth record. Persons who usually took Yorifuji et al
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Table I. Baseline characteristics of eligible children, children included in the analyses (at age 2.5 and 5.5 years), and lost to follow-up
Characteristics of children Sex, n (%)* Boys Girls Mean birth weight, g (SD)* Presence of a sibling, n (%)* 0 $1 Infant feeding practice, n (%)† Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding Parental characteristics Mean maternal age at delivery, y (SD)* Maternal smoking status, n (%)† Nonsmoker Smoker Unknown Presence of concern or worry in raising children, n (%)† Much Some Little Unknown
Eligible children (n = 41 188)
Children analyzed at age 2.5 y (n = 37 637)
Children lost to follow-up at age 2.5 y (n = 3551)
Children analyzed at age 5.5 y (n = 33 975)
Lost to follow-up at age 5.5 y (n = 7213)
21 478 (52.2) 19 710 (47.9) 3123 (340.0)
19 599 (52.1) 18 038 (47.9) 3123 (340.0)
1879 (52.9) 1672 (47.1) 3124 (342.1)
17 708 (52.1) 16 267 (47.9) 3122 (339.0)
3770 (52.3) 3443 (47.7) 3126 (345.6)
20 198 (49.0) 20 990 (51.0)
18 442 (49.0) 19 195 (51.0)
1756 (49.5) 1795 (50.6)
16 541 (48.7) 17 434 (51.3)
3657 (50.7) 3556 (49.3)
2411 (5.9)
2102 (5.6)
309 (8.7)
1847 (5.4)
564 (7.8)
8047 (19.5) 8154 (19.8) 13 389 (32.5) 9187 (22.3)
7003 (18.6) 7398 (19.7) 12 524 (33.3) 8610 (22.9)
1044 (29.4) 756 (21.3) 865 (24.4) 577 (16.3)
6137 (18.1) 6629 (19.5) 11 486 (33.8) 7876 (23.2)
1910 (26.5) 1525 (21.1) 1903 (26.4) 1311 (18.2)
29.9 (4.5)
30.1 (4.4)
28.2 (4.9)
30.2 (4.3)
28.4 (4.8)
33 919 (82.4) 7045 (17.1) 224 (0.5)
31 625 (84.0) 5835 (15.5) 177 (0.5)
2294 (64.6) 1210 (34.1) 47 (1.3)
28 938 (85.2) 4891 (14.4) 146 (0.4)
4981 (69.1) 2154 (29.9) 78 (1.1)
2598 (6.3) 22 819 (55.4) 15 655 (38.0) 116 (0.3)
2369 (6.3) 20 929 (55.6) 14 250 (37.9) 89 (0.2)
229 (6.5) 1890 (53.2) 1405 (39.6) 27 (0.8)
2135 (6.3) 18 972 (55.8) 12 795 (37.7) 73 (0.2)
463 (6.4) 3847 (53.3) 2860 (39.7) 43 (0.6)
*Obtained from the birth record. †Obtained from the first survey (at age 6 mo).
care of children were queried in the third survey (at age 2.5 years), and we assumed that children who cared for by nursery teachers to be attending day care. Maternal smoking status was ascertained at the first survey. The presence of concern or worry regarding raising children was also queried at the first survey and categorized as much, some, and little. Maternal educational attainment was obtained from the second survey (at age 18 months). We reclassified the original 8 categories into 4 as follows: junior high school or others, high school, junior college (2 years) or vocational school, and university (4 years) or higher. The mother’s income earned from work during the year of the child’s birth was queried at the second survey, so a mother with income was assumed to be working. We excluded missing cases and conducted our analyses with complete cases. In the sensitivity analyses, we further adjusted for the following variables in addition to the same set of covariates in model 3: paternal annual income during the year of the child’s birth, obtained at the second survey (as a continuous variable); whether parents made a conscious effort to talk to the child, as an indicator of parental stimulation, obtained at the first survey (dichotomous); and the child’s tendency to become sick, obtained at the first survey (dichotomous). These variables were also considered important potential confounding variables in the previous studies.5,10,12,13,16,18 Furthermore, to reduce the likelihood of reverse causation (ie, children who have disabilities might not be able to estab-
lish breastfeeding), we excluded children who had visited a clinic or hospital for congenital disease between age 7 and 18 months and repeated the same analysis in model 3. We had no information on visits before age 6 months. All CIs were calculated at the 95% level. Stata SE version 12 (StataCorp, College Station, Texas) was used for all analyses. This study was approved by the Institutional Review Board of the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences (#486).
Results Table I presents baseline characteristics from the birth record and the first survey of eligible children, children included in the analysis, and children lost to follow-up. Among the eligible children, more than 22% were in the exclusive breastfeeding category, and only 5.9% were in the formula feeding category. Compared with the eligible children, children who were lost to follow-up between the first and third surveys were more likely to have been formula-fed and to have mothers who smoked. The same tendency was observed for children who were lost to follow-up between the first and sixth surveys. Table II presents the demographic characteristics of the children included in the analysis at age 2.5 years according to infant feeding practice. Compared with children who had been formula fed, children in the exclusive breastfeeding
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Table II. Demographic characteristics of children included in the analysis at age 2.5 years according to infant feeding practice (n = 37 637)
Characteristics of children Sex, n (%)* Boys Girls Mean birth weight, g (SD)* Presence of a sibling, n (%)* 0 $1 Day care attendance, n (%)† No Yes Parental characteristics Mean maternal age at delivery, y (SD)* Maternal educational attainment, n (%)z University or higher Junior college High school Junior high school or other Missing Maternal smoking status, n (%)x Nonsmoker Smoker Unknown Maternal working status, n (%)z No Yes Missing Presence of concern or worry regarding raising children, n (%)x Much Some Little Unknown
Partial breastfeeding, breastfeeding duration
Formula feeding (n = 2102)
1-2 mo (n = 7003)
3-5 mo (n = 7398)
1128 (53.7) 974 (46.3) 3118 (362.0)
3684 (52.6) 3319 (47.4) 3110 (344.0)
3740 (50.6) 3658 (49.5) 3117 (337.0)
6661 (53.2) 5863 (46.8) 3124 (336.0)
4386 (50.9) 4224 (49.1) 3138 (337.0)
1026 (48.8) 1076 (51.2)
3389 (48.4) 3614 (51.6)
3857 (52.1) 3541 (47.9)
6726 (53.7) 5798 (46.3)
3444 (40.0) 5166 (60.0)
1550 (73.7) 552 (26.3)
4875 (69.6) 2128 (30.4)
5349 (72.3) 2049 (27.7)
9343 (74.6) 3181 (25.4)
6544 (76.0) 2066 (24.0)
30.1 (5.0)
29.4 (4.7)
29.7 (4.5)
30.6 (4.2)
30.3 (4.1)
127 (6.0) 628 (29.9) 1059 (50.4) 185 (8.8) 103 (4.9)
533 (7.6) 2317 (33.1) 3385 (48.3) 451 (6.4) 317 (4.5)
868 (11.7) 2941 (39.8) 3038 (41.1) 284 (3.8) 267 (3.6)
2164 (17.3) 5545 (44.3) 4235 (33.8) 286 (2.3) 294 (2.4)
1500 (17.4) 3840 (44.6) 2871 (33.3) 188 (2.2) 211 (2.5)
1494 (71.1) 585 (27.8) 23 (1.1)
4932 (70.4) 2036 (29.1) 35 (0.5)
5960 (80.6) 1402 (19.0) 36 (0.5)
11 325 (90.4) 1147 (9.2) 52 (0.4)
7914 (91.9) 665 (7.7) 31 (0.4)
483 (23.0) 1519 (72.3) 100 (4.8)
1917 (27.4) 4796 (68.5) 290 (4.1)
2003 (27.1) 5138 (69.5) 257 (3.5)
3341 (26.7) 8932 (71.3) 251 (2.0)
1889 (21.9) 6540 (76.0) 181 (2.1)
176 (8.4) 1079 (51.3) 839 (39.9) 8 (0.4)
464 (6.6) 3744 (53.5) 2777 (39.7) 18 (0.3)
446 (6.0) 4096 (55.4) 2839 (38.4) 17 (0.2)
811 (6.5) 7304 (58.3) 4385 (35.0) 24 (0.2)
472 (5.5) 4706 (54.7) 3410 (39.6) 22 (0.3)
6-7 mo (n = 12 524)
Exclusive breastfeeding (n = 8610)
*Obtained from the birth record. †Obtained from the third survey (at age 2.5 y). zObtained from the second survey (at age 18 mo). xObtained from the first survey (at age 6 mo).
category were more likely to have siblings, mothers with higher academic attainment, nonsmoking mothers, and parents with few concerns regarding raising children. The same tendencies were observed for children included in the analysis at age 5.5 years (Table III; available at www.jpeds. com). Table IV presents associations between infant feeding practice at age 6-7 months and behavioral development outcomes at age 2.5 years. Children who were breastfed were less likely to demonstrate developmental delays in behavior, such as being unable to climb stairs or to say his or her own name. Even after adjusting for all covariates (model 3), the protective associations remained for exclusive breastfeeding as well as for partial breastfeeding with a longer duration of breastfeeding, and most of the ORs for exclusive breastfeeding were smaller than those for partial breastfeeding. For example, compared with the formula-fed group, the OR for being unable to say his or her own name were 0.61 (95% CI, 0.53-0.71) for exclusive breastfeeding, compared with 0.66 (95% CI, 0.57-0.77) for partial breastfeeding with breastfeeding duration of 6-7 months, 0.85 (95% CI, 0.73-0.99) with duration of 1022
3-5 months, and 0.83 (95% CI, 0.72-0.97) with duration of 1-2 months. We also observed a dose–response relationship between breastfeeding status and the inability to perform ageappropriate behaviors at age 5.5 years (Table V). For example, compared with the formula-fed group, the ORs for inability to listen without fidgeting were 0.64 (95% CI, 0.56-0.73) for exclusive breastfeeding, 0.74 (95% CI, 0.66-0.85) for partial breastfeeding with breastfeeding duration of 6-7 months, 0.79 (95% CI, 0.69-0.90) for partial breastfeeding with breastfeeding duration of 3-5 months, and 0.95 (95% CI, 0.84-1.09) for partial breastfeeding with breastfeeding duration of 1-2 months. In the sensitivity analyses, even after further adjustment for paternal income, the indicator of parental stimulation, or the child’s tendency to become sick, as well as the covariates in model 3, the main findings did not change substantially (Tables VI and VII; available at www.jpeds.com). In addition, 745 children with congenital disease were excluded from the further sensitivity analyses at age 2.5 years, and 676 such children were excluded at age Yorifuji et al
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Table IV. Associations of infant feeding practice with behavioral development at age 2.5 years Cases with behavioral problems, n (%) Unable to climb stairs Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to compose a 2-phrase sentence Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to say his or her own name Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to use a spoon to eat Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo
Model 1: Crude model
Model 2: Adjusted model*
Model 3: Fully adjusted model†
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 37 411)z 1 (ref)
(n = 37 411) 1 (ref)
(n = 35 991) 1 (ref)
0.68 (0.50-0.92) 0.66 (0.49-0.90) 0.53 (0.40-0.71) 0.50 (0.37-0.68) (n = 37 047) 1 (ref)
0.68 (0.50-0.93) 0.65 (0.48-0.88) 0.51 (0.38-0.69) 0.53 (0.39-0.73) (n = 37 047) 1 (ref)
0.69 (0.50-0.94) 0.64 (0.47-0.88) 0.49 (0.36-0.66) 0.52 (0.38-0.72) (n = 35 991) 1 (ref)
0.71 (0.57-0.87) 0.68 (0.55-0.83) 0.53 (0.43-0.65) 0.43 (0.35-0.54) (n = 37 371) 1 (ref)
0.73 (0.59-0.91) 0.70 (0.56-0.86) 0.52 (0.42-0.64) 0.44 (0.35-0.55) (n = 37 371) 1 (ref)
0.74 (0.59-0.92) 0.71 (0.57-0.89) 0.50 (0.41-0.63) 0.43 (0.34-0.55) (n = 35 952) 1 (ref)
52 (2.5)
0.75 (0.65-0.87) 0.76 (0.66-0.87) 0.65 (0.57-0.74) 0.59 (0.51-0.68) (n = 37 424)z 1 (ref)
0.77 (0.67-0.89) 0.78 (0.68-0.90) 0.63 (0.55-0.73) 0.58 (0.50-0.67) (n = 37 424) 1 (ref)
0.83 (0.72-0.97) 0.85 (0.73-0.99) 0.66 (0.57-0.77) 0.61 (0.53-0.71) (n = 36 006) 1 (ref)
117 (1.7) 144 (2.0) 225 (1.8) 114 (1.3)
0.67 (0.48-0.93) 0.78 (0.57-1.07) 0.72 (0.53-0.97) 0.53 (0.38-0.73)
0.71 (0.51-0.99) 0.81 (0.58-1.12) 0.70 (0.52-0.96) 0.58 (0.41-0.80)
0.76 (0.54-1.08) 0.85 (0.60-1.19) 0.69 (0.50-0.96) 0.58 (0.40-0.82)
61 (2.9) 139 (2.0) 144 (2.0) 196 (1.6) 127 (1.5) 127 (6.0) 305 (4.4) 309 (4.2) 414 (3.3) 235 (2.7) 311 (14.8) 811 (11.6) 865 (11.7) 1270 (10.1) 804 (9.3)
*Adjusted for child factors (sex, birth weight, presence of a sibling, and day care attendance). †Adjusted for child factors as well as parental factors (maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). zNumber of included cases in each analysis.
5.5 years. The protective effects were slightly attenuated at age 2.5 years, but the main findings did not change substantially (Tables VI and VII).
Discussion In the present study, we prospectively examined associations between breastfeeding (data obtained at age 67 months) and behavioral development outcomes at age 2.5 and 5.5 years using a large Japanese nationwide population-based longitudinal survey. We observed a clear dose–response relationship between breastfeeding status and the inability to perform age-appropriate developmental behavior skills surveyed at both ages. The protective associations did not change even after we adjusted for an extensive list of potential confounders or in the sensitivity analyses. This is the largest published study to date examining the association between breastfeeding and behavioral development. Behavioral development outcomes at age 2.5 years are related to gross and fine motor development, as well as to verbal development. We observed protective effects on these outcomes with longer duration of breastfeeding. This finding is consistent with previous studies demonstrating potential benefits for motor and verbal development.8,13,23-26 The present study supports those previous findings with a large sam-
ple size, a clear dose–response relationship, and adjustment for a number of potential confounders. We also observed protective effects of breastfeeding on behavioral development at age 5.5 years, related to social and self-regulatory development. Previous observational studies similarly demonstrated potential benefits on these behavioral developments, including adaptability or communication at age 1 year,13 attention-hyperactivity behaviors and social behavior at age 4 years,11 behavior scores for 5 areas of child behavior at age 5 years,10 and behaviors obtained by the Child Behavior Checklist at age 14 years.12 The large RCT in Belarus mentioned earlier found no protective effect on social and self-regulatory behavior at age 6.5 years in an intention-to-treat analysis comparing a breastfeeding promotion group and a control group.18,19 Although we cannot totally exclude the possibility of residual confounding in our study or previous observational studies, the RCT also may suffer from nondifferential exposure misclassification between the 2 groups, possibly moving effect estimates toward the null, attenuating the results.27 An absence of association in the RCT does not nullify all of the findings observed in the observational studies. Based on our data, we believe that there are at least 3 reasons for the protective effects of breastfeeding on behavioral development. First, the biological ingredients of breast milk may play a role. Breast milk contains long-chain
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Table V. Associations of infant feeding practice with behavioral development at age 5.5 years Cases with a behavioral problem, n (%) Unable to listen without fidgeting Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to focus on one task Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to remain patient Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to express emotions Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to act in a group Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to keep promises Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo
Model 1: Crude model
Model 2: Adjusted model*
Model 3: Fully adjusted model†
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 33 473)z 1 (ref)
(n = 33 473) 1 (ref)
(n = 32 588) 1 (ref)
0.95 (0.83-1.07) 0.75 (0.66-0.85) 0.68 (0.60-0.77) 0.53 (0.47-0.60) (n = 33 525) 1 (ref)
0.96 (0.84-1.09) 0.75 (0.66-0.86) 0.66 (0.59-0.75) 0.56 (0.49-0.63) (n = 33 525) 1 (ref)
0.95 (0.84-1.09) 0.79 (0.69-0.90) 0.74 (0.66-0.85) 0.64 (0.56-0.73) (n = 32 640) 1 (ref)
0.86 (0.75-1.00) 0.80 (0.69-0.92) 0.66 (0.58-0.76) 0.52 (0.45-0.60) (n = 33 349) 1 (ref)
0.87 (0.75-1.00) 0.79 (0.68-0.91) 0.65 (0.56-0.74) 0.54 (0.47-0.63) (n = 33 349) 1 (ref)
0.88 (0.76-1.02) 0.86 (0.74-0.99) 0.76 (0.66-0.87) 0.65 (0.56-0.75) (n = 32 467) 1 (ref)
0.80 (0.71-0.89) 0.72 (0.64-0.80) 0.62 (0.56-0.69) 0.54 (0.48-0.61) (n = 33 320)z 1 (ref)
0.80 (0.71-0.90) 0.73 (0.65-0.82) 0.63 (0.56-0.70) 0.54 (0.48-0.60) (n = 33 320) 1 (ref)
0.81 (0.72-0.92) 0.77 (0.69-0.87) 0.68 (0.61-0.76) 0.60 (0.53-0.67) (n = 32 441) 1 (ref)
0.84 (0.74-0.95) 0.90 (0.80-1.02) 0.84 (0.75-0.95) 0.72 (0.64-0.81) (n = 33 475) 1 (ref)
0.84 (0.75-0.95) 0.90 (0.80-1.02) 0.83 (0.74-0.93) 0.75 (0.67-0.85) (n = 33 475) 1 (ref)
0.84 (0.74-0.96) 0.92 (0.81-1.04) 0.84 (0.74-0.94) 0.76 (0.67-0.86) (n = 32 593) 1 (ref)
469 (25.4)
0.85 (0.70-1.02) 0.72 (0.59-0.87) 0.61 (0.51-0.73) 0.57 (0.47-0.68) (n = 33 171) 1 (ref)
0.86 (0.71-1.03) 0.73 (0.60-0.88) 0.60 (0.50-0.72) 0.59 (0.49-0.72) (n = 33 171) 1 (ref)
0.86 (0.71-1.04) 0.75 (0.62-0.91) 0.64 (0.53-0.77) 0.63 (0.51-0.76) (n = 32 297) 1 (ref)
1368 (22.3) 1320 (19.9) 2028 (17.7) 1235 (15.7)
0.84 (0.74-0.94) 0.72 (0.64-0.82) 0.63 (0.56-0.70) 0.54 (0.48-0.61)
0.84 (0.74-0.95) 0.73 (0.64-0.82) 0.62 (0.55-0.70) 0.56 (0.49-0.63)
0.83 (0.73-0.94) 0.77 (0.68-0.87) 0.70 (0.62-0.79) 0.63 (0.56-0.72)
413 (22.4) 1319 (21.5) 1182 (17.8) 1885 (16.4) 1052 (13.4) 312 (16.9) 919 (15.0) 930 (14.0) 1364 (11.9) 760 (9.7) 596 (32.3) 1694 (27.6) 1696 (25.6) 2645 (23.0) 1624 (20.6) 466 (25.2) 1363 (22.2) 1555 (23.5) 2560 (22.3) 1547 (19.6) 160 (8.7) 460 (7.5) 428 (6.5) 634 (5.5) 406 (5.2)
*Adjusted for child factors (sex, birth weight, and presence of a sibling). †Adjusted for child factors as well as parental factors (maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). zNumber of included cases in each analysis.
polyunsaturated fatty acids, particularly docosahexaenoic acid and arachidonic acid, which are considered to be positively associated with cognitive and behavioral functions.28 Although formula milk in Japan has been supplemented with docosahexaenoic acid or arachidonic acid in recent years, the levels of these fatty acids did not reach those provided by breastfeeding in 2001. Second, mothers who breastfeed are likely to spend more time with their babies than those who formula feed. Extensive interactions through breastfeeding may have promoted the shaping of brain circuitry in the infant as well as developing strong mother–infant bonding, which creates the foundation for later development.29 Third, there is the possibility of a biased association because of residual confounding. We extensively adjusted for potential confounders in the main analyses, however. 1024
Furthermore, we examined other potential confounders in the sensitivity analyses and found no significant change in the results. Thus, it is unlikely that our present findings can be totally attributed to residual confounding. A strength of the present study is the large, nationally representative sample. Roughly one-twentieth of the children born in Japan in 2001 are included in this survey. The large sample size allowed us to examine the dose–response relationship between breastfeeding and behavioral development outcomes. In addition, the very high response rate at baseline strengthens the validity of our findings. The duration of breastfeeding should be accurate, because the information on feeding practice was collected at the first survey (ie, when the children were aged 6-7 months); however, we could not evaluate the effect of both partial and exclusive breastfeeding beyond 6-7 months. Yorifuji et al
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May 2014 The uncertainty of the external validation of questions used to assess the behavioral outcomes poses a threat to the validity of our findings. Moreover, because of the subjective nature of these questions, we cannot exclude the possibility of misclassification of behavioral outcomes. Any misclassification would be nondifferential, however, moving the effect estimates toward the null. Loss to follow-up may be a concern. Because loss was more common in higher-risk groups, such as formula-fed children and mothers who smoked, we may be underestimating the protective effects of breastfeeding on developmental outcomes. Finally, a reverse causation (ie, children who originally had disabilities might not be able to establish breastfeeding) would be unlikely, because the findings were robust in the sensitivity analyses, which excluded children with congenital disease. In conclusion, although we are not certain whether a biological ingredient of breast milk, extensive mother–child interactions through breastfeeding, or both are beneficial, we observed prolonged effects of breastfeeding on developmental behavior skills surveyed at age 2.5 and 5.5 years. n We appreciate valuable comments by Dr Satoshi Sanada and Ms Midory Higa Diez. We thank Ms Saori Irie for her support. Submitted for publication Sep 27, 2013; last revision received Dec 10, 2013; accepted Jan 7, 2014. Reprint requests: Takashi Yorifuji, MD, PhD, Department of Human Ecology, Okayama University Graduate School of Environmental and Life Science, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. E-mail: yorichan@ md.okayama-u.ac.jp
References 1. World Health Organization. Global strategy for infant and young child feeding: the optimal duration of exclusive breastfeeding. Geneva, Switzerland: World Health Organization; 2001. 2. Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev 2012;CD003517. 3. Quigley MA, Kelly YJ, Sacker A. Breastfeeding and hospitalization for diarrheal and respiratory infection in the United Kingdom Millennium Cohort Study. Pediatrics 2007;119:e837-42. 4. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. Lancet 2000;355:451-5. 5. Horta B, Victor C. Long-term effects of breastfeeding: A systematic review. Geneva, Switzerland: World Health Organization; 2013. 6. Britton JR, Britton HL, Gronwaldt V. Breastfeeding, sensitivity, and attachment. Pediatrics 2006;118:e1436-43. 7. Anderson JW, Johnstone BM, Remley DT. Breast-feeding and cognitive development: a meta-analysis. Am J Clin Nutr 1999;70:525-35. 8. Eickmann SH, de Lira PI, Lima Mde C, Coutinho SB, Teixeira Mde L, Ashworth A. Breast feeding and mental and motor development at 12 months in a low-income population in northeast Brazil. Paediatr Perinat Epidemiol 2007;21:129-37. 9. Hart S, Boylan LM, Carroll S, Musick YA, Lampe RM. Brief report: breast-fed one-week-olds demonstrate superior neurobehavioral organization. J Pediatr Psychol 2003;28:529-34.
10. Heikkila K, Sacker A, Kelly Y, Renfrew MJ, Quigley MA. Breast feeding and child behaviour in the Millennium Cohort Study. Arch Dis Child 2011;96:635-42. 11. Julvez J, Ribas-Fito N, Forns M, Garcia-Esteban R, Torrent M, Sunyer J. Attention behaviour and hyperactivity at age 4 and duration of breastfeeding. Acta Paediatr 2007;96:842-7. 12. Oddy WH, Kendall GE, Li J, Jacoby P, Robinson M, de Klerk NH, et al. The long-term effects of breastfeeding on child and adolescent mental health: a pregnancy cohort study followed for 14 years. J Pediatr 2010; 156:568-74. 13. Oddy WH, Robinson M, Kendall GE, Li J, Zubrick SR, Stanley FJ. Breastfeeding and early child development: a prospective cohort study. Acta Paediatr 2011;100:992-9. 14. Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Higgins RD, Langer JC, et al. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics 2007;120:e953-9. 15. Der G, Batty GD, Deary IJ. Effect of breast feeding on intelligence in children: prospective study, sibling pairs analysis, and meta-analysis. BMJ 2006;333:945. 16. Holme A, MacArthur C, Lancashire R. The effects of breastfeeding on cognitive and neurological development of children at 9 years. Child Care Health Dev 2010;36:583-90. 17. Kramer MS, Aboud F, Mironova E, Vanilovich I, Platt RW, Matush L, et al. Breastfeeding and child cognitive development: new evidence from a large randomized trial. Arch Gen Psychiatry 2008;65:578-84. 18. Kramer MS, Fombonne E, Matush L, Bogdanovich N, Dahhou M, Platt RW. Long-term behavioural consequences of infant feeding: the limits of observational studies. Paediatr Perinat Epidemiol 2011;25: 500-6. 19. Kramer MS, Fombonne E, Igumnov S, Vanilovich I, Matush L, Mironova E, et al. Effects of prolonged and exclusive breastfeeding on child behavior and maternal adjustment: evidence from a large, randomized trial. Pediatrics 2008;121:e435-40. 20. Yamakawa M, Yorifuji T, Inoue S, Kato T, Doi H. Breastfeeding and obesity among schoolchildren: a nationwide longitudinal survey in Japan. JAMA Pediatr 2013;167:919-25. 21. Kato T, Yorifuji T, Inoue S, Yamakawa M, Doi H, Kawachi I. Associations of preterm births with child health and development: a Japanese population-based study. J Pediatr 2013;163:1578-84. 22. Kato T, Yorifuji T, Inoue S, Doi H, Kawachi I. Association of birth length and risk of hospitalisation among full-term babies in Japan. Paediatr Perinat Epidemiol 2013;27:361-70. 23. Dee DL, Li R, Lee LC, Grummer-Strawn LM. Associations between breastfeeding practices and young children’s language and motor skill development. Pediatrics 2007;119(Suppl 1):S92-8. 24. McCrory C, Murray A. The effect of breastfeeding on neurodevelopment in infancy. Matern Child Health J 2012;17:1680-8. 25. Sacker A, Quigley MA, Kelly YJ. Breastfeeding and developmental delay: findings from the millennium cohort study. Pediatrics 2006;118:e682-9. 26. Whitehouse AJ, Robinson M, Li J, Oddy WH. Duration of breast feeding and language ability in middle childhood. Paediatr Perinat Epidemiol 2010;25:44-52. 27. Rothman KJ. Epidemiology: An introduction. 2nd ed. New York: Oxford University Press; 2012. 28. McCann JC, Ames BN. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr 2005;82:281-95. 29. National Scientific Council on the Developing Child. The timing and quality of early experiences combine to shape brain architecture: Working Paper 5; 2007. Available from: http://www.developingchild.net. Accessed July 22, 2013.
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All babies born between the 10th and 17th of January or the 10th and 17th of July in 2001 in Japan: n = 53 575
Questionnaire returned at the first survey: n = 47 015 Exclusion (n = 5125) - Children < 37 gestational weeks: n = 2418 - Birth weight < 2500 g: n = 2464 - Twins or triplets: n = 243 Feeding practice information missing (n = 702) Eligible children: n = 41 188
Lost to follow up at the third survey (n = 3551)
Lost to follow up at the sixth survey (n = 7213)
Children included in the analyses - Age 2.5 years (3rd survey): n = 37 637 - Age 5.5 years (6th survey): n = 33 975
Figure. Flow chart of study participants.
Table III. Demographic characteristics of children included in the analysis at age 5.5 years according to infant feeding practice (n = 33 975)
Characteristics of children Sex, n (%)* Boys Girls Mean birth weight, g (SD)* Presence of a sibling, n (%)* 0 $1 Parental characteristics Mean maternal age at delivery, y (SD)* Maternal educational attainment, n (%)† University or higher Junior college High school Junior high school or other Missing Maternal smoking status, n (%)z Nonsmoker Smoker Unknown Maternal working status, n (%)† No Yes Missing Presence of concern or worry regarding raising children, n (%)z Much Some Little Unknown
Partial breastfeeding, breastfeeding duration
Formula feeding (n = 1847)
1-2 mo (n = 6137)
3-5 mo (n = 6629)
1000 (54.1) 847 (45.9) 3122 (360.0)
3234 (52.7) 2903 (47.3) 3109 (344.0)
3343 (50.4) 3286 (49.6) 3115 (336.0)
6117 (53.3) 5369 (46.7) 3123 (336.0)
4014 (51.0) 3862 (49.0) 3139 (335.0)
900 (48.7) 947 (51.3)
2936 (47.8) 3201 (52.2)
3437 (51.9) 3192 (48.2)
6134 (53.4) 5352 (46.6)
3134 (39.8) 4742 (60.2)
30.3 (4.9)
29.6 (4.6)
29.9 (4.4)
30.7 (4.2)
30.4 (4.0)
118 (6.4) 569 (30.8) 949 (51.4) 148 (8.0) 63 (3.4)
497 (8.1) 2125 (34.6) 2985 (48.6) 360 (5.9) 170 (2.8)
826 (12.5) 2721 (41.1) 2706 (40.8) 218 (3.3) 158 (2.4)
2071 (18.0) 5179 (45.1) 3837 (33.4) 226 (2.0) 173 (1.5)
1420 (18.0) 3587 (45.5) 2583 (32.8) 154 (2.0) 132 (1.7)
1341 (72.6) 487 (26.4) 19 (1.0)
4431 (72.2) 1678 (27.3) 28 (0.5)
5414 (81.7) 1182 (17.8) 33 (0.5)
10 460 (91.1) 985 (8.6) 41 (0.4)
7292 (92.6) 559 (7.1) 25 (0.3)
441 (23.9) 1347 (72.9) 59 (3.2)
1717 (28.0) 4269 (69.6) 151 (2.5)
1837 (27.7) 4644 (70.1) 148 (2.2)
3101 (27.0) 8251 (71.8) 134 (1.2)
1765 (22.4) 6006 (76.3) 105 (1.3)
150 (8.1) 961 (52.0) 732 (39.6) 4 (0.2)
408 (6.7) 3288 (53.6) 2427 (39.6) 14 (0.2)
402 (6.1) 3699 (55.8) 2512 (37.9) 16 (0.2)
733 (6.4) 6728 (58.6) 4006 (34.9) 19 (0.2)
442 (5.6) 4296 (54.6) 3118 (39.6) 20 (0.3)
6-7 mo (n = 11 486)
Exclusive breastfeeding (n = 7876)
*Obtained from the birth record. †Obtained from the second survey (at age 18 mo). zObtained from the first survey (at age 6 mo).
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Table VI. Sensitivity analyses at age 2.5 years Model 3* plus paternal Model 3* plus parental Model 3* plus child tendency Model 3* (Exclusion of children income† stimulation† to become sick† with congenital disease) OR (95% CI) Unable to climb stairs (n = 35 377)z Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.69 (0.50-0.95) 3-5 mo 0.65 (0.47-0.89) 6-7 mo 0.48 (0.36-0.65) Exclusive breastfeeding at age 6-7 mo 0.54 (0.39-0.74) Unable to compose a 2-phrase sentence (n = 35 378) Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.73 (0.58-0.91) 3-5 mo 0.71 (0.57-0.89) 6-7 mo 0.50 (0.41-0.63) Exclusive breastfeeding at age 6-7 mo 0.43 (0.34-0.54) Unable to say his or her own name (n = 35 339) Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.83 (0.71-0.96) 3-5 mo 0.85 (0.73-0.99) 6-7 mo 0.66 (0.57-0.76) Exclusive breastfeeding at age 6-7 mo 0.61 (0.52-0.71) Unable to use a spoon to eat (n = 35 394)z Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.75 (0.53-1.06) 3-5 mo 0.84 (0.60-1.18) 6-7 mo 0.69 (0.50-0.95) Exclusive breastfeeding at age 6-7 mo 0.58 (0.40-0.82)
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 35 991) 1 (ref)
(n = 35 991) 1 (ref)
(n = 35 258) 1 (ref)
0.69 (0.51-0.94) 0.65 (0.47-0.88) 0.49 (0.36-0.66) 0.53 (0.38-0.73) (n = 35 991) 1 (ref)
0.70 (0.51-0.95) 0.65 (0.48-0.89) 0.50 (0.37-0.68) 0.55 (0.40-0.75) (n = 35 991) 1 (ref)
0.73 (0.51-1.04) 0.80 (0.57-1.14) 0.62 (0.44-0.87) 0.68 (0.48-0.97) (n = 35 259) 1 (ref)
0.75 (0.60-0.93) 0.72 (0.57-0.89) 0.51 (0.41-0.63) 0.44 (0.35-0.55) (n = 35 952) 1 (ref)
0.74 (0.60-0.93) 0.71 (0.57-0.89) 0.51 (0.41-0.64) 0.44 (0.35-0.56) (n = 35 952) 1 (ref)
0.76 (0.60-0.96) 0.77 (0.61-0.98) 0.57 (0.45-0.71) 0.49 (0.39-0.63) (n = 35 221) 1 (ref)
0.84 (0.72-0.98) 0.86 (0.74-1.00) 0.67 (0.58-0.78) 0.62 (0.53-0.72) (n = 36 006) 1 (ref)
0.84 (0.72-0.97) 0.85 (0.73-0.99) 0.67 (0.58-0.77) 0.62 (0.53-0.72) (n = 36 006) 1 (ref)
0.84 (0.72-0.99) 0.88 (0.76-1.03) 0.69 (0.59-0.80) 0.65 (0.55-0.76) (n = 35 273) 1 (ref)
0.77 (0.54-1.09) 0.85 (0.61-1.20) 0.70 (0.51-0.97) 0.58 (0.41-0.83)
0.77 (0.54-1.09) 0.86 (0.61-1.21) 0.72 (0.52-0.99) 0.60 (0.42-0.85)
0.86 (0.58-1.26) 1.04 (0.71-1.51) 0.87 (0.60-1.24) 0.74 (0.50-1.09)
*Adjusted for child factors as well as parental factors (sex, birth weight, presence of a sibling, day care attendance, maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). †Further adjusted for each variable in the fully adjusted model (model 3). zNumber of included cases in each analysis.
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Table VII. Sensitivity analyses at age 5.5 years Model 3* plus paternal income†
Model 3* plus parental stimulation†
Model 3* plus child tendency to become sick†
Model 3* (exclusion of children with congenital disease)
Unable to listen carefully Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to focus on one task Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to remain patient Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to express emotions Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to act in a group Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to keep promises Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo
OR (95% CI)
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 32 064)z 1 (ref)
(n = 32 588) 1 (ref)
(n = 32 588) 1 (ref)
(n = 31 936) 1 (ref)
0.95 (0.83-1.08) 0.79 (0.69-0.90) 0.74 (0.65-0.84) 0.63 (0.55-0.72) (n = 32 118) 1 (ref)
0.96 (0.84-1.10) 0.80 (0.70-0.91) 0.75 (0.66-0.85) 0.65 (0.56-0.74) (n = 32 640) 1 (ref)
0.96 (0.84-1.09) 0.79 (0.69-0.90) 0.75 (0.66-0.85) 0.64 (0.56-0.73) (n = 32 640) 1 (ref)
0.96 (0.84-1.10) 0.80 (0.70-0.91) 0.75 (0.66-0.85) 0.65 (0.56-0.74) (n = 31 985) 1 (ref)
0.86 (0.75-1.00) 0.85 (0.73-0.99) 0.75 (0.65-0.86) 0.64 (0.55-0.74) (n = 31 947) 1 (ref)
0.89 (0.77-1.02) 0.86 (0.75-1.00) 0.76 (0.66-0.88) 0.65 (0.56-0.76) (n = 32 467) 1 (ref)
0.88 (0.76-1.02) 0.86 (0.74-0.99) 0.76 (0.66-0.87) 0.65 (0.56-0.75) (n = 32 467) 1 (ref)
0.90 (0.78-1.05) 0.88 (0.76-1.02) 0.77 (0.66-0.88) 0.66 (0.57-0.77) (n = 31 818) 1 (ref)
0.81 (0.72-0.91) 0.77 (0.69-0.87) 0.67 (0.60-0.75) 0.59 (0.53-0.67) (n = 31 919)z 1 (ref)
0.82 (0.73-0.92) 0.78 (0.69-0.87) 0.68 (0.61-0.76) 0.60 (0.54-0.68) (n = 32 441) 1 (ref)
0.82 (0.73-0.92) 0.77 (0.69-0.87) 0.68 (0.61-0.76) 0.60 (0.53-0.68) (n = 32 441) 1 (ref)
0.82 (0.72-0.92) 0.78 (0.69-0.87) 0.68 (0.60-0.76) 0.60 (0.53-0.68) (n = 31 785) 1 (ref)
0.86 (0.75-0.97) 0.93 (0.82-1.05) 0.85 (0.75-0.95) 0.77 (0.68-0.88) (n = 32 073) 1 (ref)
0.85 (0.75-0.96) 0.92 (0.82-1.05) 0.85 (0.75-0.96) 0.77 (0.68-0.87) (n = 32 593) 1 (ref)
0.84 (0.74-0.96) 0.92 (0.81-1.04) 0.84 (0.75-0.95) 0.76 (0.67-0.86) (n = 32 593) 1 (ref)
0.86 (0.75-0.97) 0.93 (0.82-1.05) 0.85 (0.76-0.96) 0.77 (0.68-0.88) (n = 31 932) 1 (ref)
0.86 (0.70-1.04) 0.75 (0.61-0.91) 0.64 (0.52-0.77) 0.62 (0.51-0.76) (n = 31 779) 1 (ref)
0.87 (0.71-1.05) 0.76 (0.63-0.93) 0.65 (0.54-0.79) 0.64 (0.52-0.78) (n = 32 297) 1 (ref)
0.86 (0.71-1.05) 0.76 (0.62-0.92) 0.65 (0.54-0.78) 0.63 (0.52-0.77) (n = 32 297) 1 (ref)
0.88 (0.72-1.07) 0.78 (0.63-0.95) 0.68 (0.56-0.83) 0.67 (0.55-0.83) (n = 31 645) 1 (ref)
0.82 (0.72-0.93) 0.77 (0.68-0.87) 0.69 (0.61-0.78) 0.63 (0.55-0.72)
0.84 (0.74-0.95) 0.77 (0.68-0.88) 0.70 (0.62-0.79) 0.64 (0.56-0.72)
0.83 (0.73-0.94) 0.77 (0.68-0.87) 0.70 (0.62-0.79) 0.63 (0.56-0.72)
0.83 (0.73-0.94) 0.77 (0.68-0.87) 0.69 (0.61-0.78) 0.63 (0.56-0.72)
*Adjusted for child factors as well as parental factors (sex, birth weight, presence of a sibling, maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). †Further adjusted for each variable in the fully adjusted model (model 3). zNumber of included cases in each analysis.
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T
he World Health Organization recommends exclusive breastfeeding for the first 6 months of life,1 based on accumulated evidence of the protective effects of breastfeeding against infectious diseases (eg, gastrointestinal, respiratory).2-4 In addition, potential prolonged effects of breastfeeding on several outcomes (eg, obesity, cognitive function, dental caries) have been investigated, but the findings remain inconclusive, except for a potential benefit on cognitive function.2,5 Compared with a number of studies that examined the potential benefit of prolonged breastfeeding on several major health outcomes,2,5 few studies have investigated the potential benefit on behavioral development that might be expected because of the close contact between mothers and infants during feeding.6 Although several observational studies have suggested some benefits for several behavioral outcomes from the neonatal period to adolescence,7-14 most of these studies had a small sample size. Moreover, as discussed in studies on cognitive function,5,15-17 residual confounding is thought to explain the observed protective effect of breastfeeding on behavioral outcomes.18 Potential confounders include parental educational status, parental socioeconomic status, and variations in parental effort in teaching. Indeed, a large randomized control trial (RCT) in Belarus did not find a protective effect on behavior in the intention-to-treat analysis comparing 2 groups (breastfeeding promotion group and control group), but did identify a benefit in an observational analysis based on 5 categories of breastfeeding duration.18,19 That study indicates an inherent limitation of observational studies (a possibility of residual confounding), however; the different categorization of each method of analysis in the study calls into question the authors’ conclusions. Consequently, in the present study we prospectively examined the prolonged effect of breastfeeding on behavioral development at age 2.5 and 5.5 years using data from a large Japanese nationwide population-based longitudinal survey. We attempted to determine whether dose–response relationships exist between the duration of breastfeeding and behavioral outcomes, and adjusted for an extensive list of potential confounding variables that might induce a biased association.
Methods The Japanese Ministry of Health, Labour, and Welfare (MHLW) has been surveying parents and their newborn babies annually since 2001. This survey, the Longitudinal Survey of Babies in the 21st Century, is described in detail elsewhere.20-22 In brief, when the newborns were 6 months old, baseline questionnaires were sent to all families throughout Japan that had a baby (or babies) born on January 10-17 or July 10-17, 2001. Among the 53 575 questionnaires MHLW RCT
Japanese Ministry of Health, Labour, and Welfare Randomized control trial
From the 1Department of Human Ecology, Okayama University Graduate School of Environmental and Life Science, Okayama, Japan; 2Department of Pediatrics, Okayama Medical Center, National Hospital Organization, Okayama, Japan; 3Department of Public Health and Public Policy, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 4Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; and 5 Department of Child and Adolescent Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan Supported by Health and Labour Sciences Research (H24-Jisedai-Ippan-004). The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.01.012
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that were mailed, 47 015 were completed and returned (response rate, 88%). Every year (at age 18 months, 30 months, 42 months, and so on), follow-up questionnaires were sent to all participants who initially responded. Birth records from Japanese vital statistics are also linked to each child in this survey. Birth records data include length, weight, gestational age, singleton or twin or other multiple birth, sex, parity, and parental age. For the present study, we targeted children with data collected for the third and sixth surveys (at age 2.5 and 5.5 years, respectively). We restricted the study participants to children born after 37 gestational weeks, with a birth weight >2500 g, and singleton births, because of the potential influence of prematurity, intrauterine growth retardation, and multiples on childhood development (Figure; available at www.jpeds.com). This led to the exclusion of 5125 children from each of the 2 surveys. Children with missing information on feeding practices during infancy (n = 702) were excluded as well. At the third survey, 3551 children were lost to follow-up, leaving 37 637 children in the analysis at age 2.5 years. Similarly, at the sixth survey, 7213 children were lost to follow-up, leaving 33 975 children in the analysis at age 5.5 years. Infant Feeding Practice The first survey at age 6 months included questions on infant feeding practices to determine whether the children had been breastfed, only colostrum-fed, or formula-fed.20 The duration (in months) of breastfeeding and formula feeding was then queried. In the present study, we combined the categories of “never breastfed” and “colostrum only” into a category of “formula feeding” because of the small number in the category of “never breastfed” and the short duration of colostrum feeding (ie, approximately 1 week). We created categories of “partial breastfeeding” and “exclusive breastfeeding” using information on breastfeeding and formula feeding. We further divided the category of “partial breastfeeding” based on the duration of breastfeeding (ie, breastfeeding for 1-2 months, 3-5 months, and 6-7 months). Although the first survey was administered at age 6 months, we included a category of up to 7 months depending on the timing of the response. Children in the exclusive breastfeeding category had been breastfed for 6-7 months. Finally, we categorized the feeding practice as formula feeding, partial breastfeeding (ie, breastfeeding for 1-2 months, 3-5 months, or 6-7 months), or exclusive breastfeeding at age 6-7 months. Behavioral Development Outcomes For behavioral development outcomes, we used the survey questions that elicited information on age-appropriate behavior.21 At age 2.5 years, the following questions were asked: (1) “Can your child climb stairs?”; (2) “Can your child compose 2-phrase sentences?”; (3) “Can your child say his or her own name?”; and (4) “Can your child use a spoon to eat?” We did not use the following questions because the behaviors seemed heavily dependent on parenting practices: “Can your child brush their teeth by him/herself?,” “Does your child 1020
Vol. 164, No. 5 wear a diaper during the day?,” and “Can your child put on clothes by himself?” We also did not use the questions “Can your child walk?,” “Can your child run?,” and “Can your child say things that make sense?,” because almost all responses were affirmative (>99%). The MHLW extracted the behavioral questions used in our analyses from the “Maternal and Child Health Handbook” (“Boshi Kenko Techo”). The Handbook is a record of health and child development given to every pregnant mother in Japan in which all information from postnatal visits is recorded prospectively until the child is 6 years old. The dissemination and use of the Handbook is mandated under Japanese law and has been implemented for decades. At age 5.5 years, the following questions were asked: (1) “Can your child listen without fidgeting?”; (2) “Can your child focus on one task?”; (3) “Is your child patient?”; (4) “Can your child express emotions appropriately?”; (5) “Can your child get along with others in a group setting?”; and (6) “Can your child keep promises?” According to the MHLW, these questions were developed for this survey to capture early signs of behavioral and developmental problems. During the past decade, the MHLW has been attempting to track the prevalence of behavioral and developmental problems; however, we could not confirm whether these questions have been externally validated. Statistical Analyses To evaluate the impact of loss to follow-up (Figure), we first compared baseline characteristics among eligible children, children included in the analysis (at both the third and sixth surveys), and children lost to follow-up. We then compared baseline characteristics according to the infant feeding practices among eligible children. We conducted logistic regression analyses to evaluate the relationships between infant feeding practice and behavioral development at age 2.5 and 5.5 years. We first estimated the crude OR and 95% CI for each outcome (model 1). We then estimated the OR and 95% CI for each outcome after controlling for child factors (model 2) and for both child and parental factors (model 3). Throughout the analyses, the formula feeding group served as the reference group. In the analyses, we controlled for potential confounding factors related to the children and parents based on a review5 or previous original studies10,12,13,16,18 that examined the associations between breastfeeding and cognitive functions or behavioral outcomes. In children, these factors included sex (dichotomous), birth weight (continuous), presence of a sibling (dichotomous), and day care attendance (dichotomous, only in the analysis at age 2.5 years). Parental factors included maternal age at delivery (continuous), maternal smoking habits (dichotomous), parental concern or worry regarding raising children (categorical), maternal educational attainment (categorical), and maternal working status (dichotomous). The child’s sex and birth weight and maternal age at delivery were listed in the birth record. The presence of a sibling was obtained from the information on parity (ie, number of deliveries) in the birth record. Persons who usually took Yorifuji et al
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Table I. Baseline characteristics of eligible children, children included in the analyses (at age 2.5 and 5.5 years), and lost to follow-up
Characteristics of children Sex, n (%)* Boys Girls Mean birth weight, g (SD)* Presence of a sibling, n (%)* 0 $1 Infant feeding practice, n (%)† Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding Parental characteristics Mean maternal age at delivery, y (SD)* Maternal smoking status, n (%)† Nonsmoker Smoker Unknown Presence of concern or worry in raising children, n (%)† Much Some Little Unknown
Eligible children (n = 41 188)
Children analyzed at age 2.5 y (n = 37 637)
Children lost to follow-up at age 2.5 y (n = 3551)
Children analyzed at age 5.5 y (n = 33 975)
Lost to follow-up at age 5.5 y (n = 7213)
21 478 (52.2) 19 710 (47.9) 3123 (340.0)
19 599 (52.1) 18 038 (47.9) 3123 (340.0)
1879 (52.9) 1672 (47.1) 3124 (342.1)
17 708 (52.1) 16 267 (47.9) 3122 (339.0)
3770 (52.3) 3443 (47.7) 3126 (345.6)
20 198 (49.0) 20 990 (51.0)
18 442 (49.0) 19 195 (51.0)
1756 (49.5) 1795 (50.6)
16 541 (48.7) 17 434 (51.3)
3657 (50.7) 3556 (49.3)
2411 (5.9)
2102 (5.6)
309 (8.7)
1847 (5.4)
564 (7.8)
8047 (19.5) 8154 (19.8) 13 389 (32.5) 9187 (22.3)
7003 (18.6) 7398 (19.7) 12 524 (33.3) 8610 (22.9)
1044 (29.4) 756 (21.3) 865 (24.4) 577 (16.3)
6137 (18.1) 6629 (19.5) 11 486 (33.8) 7876 (23.2)
1910 (26.5) 1525 (21.1) 1903 (26.4) 1311 (18.2)
29.9 (4.5)
30.1 (4.4)
28.2 (4.9)
30.2 (4.3)
28.4 (4.8)
33 919 (82.4) 7045 (17.1) 224 (0.5)
31 625 (84.0) 5835 (15.5) 177 (0.5)
2294 (64.6) 1210 (34.1) 47 (1.3)
28 938 (85.2) 4891 (14.4) 146 (0.4)
4981 (69.1) 2154 (29.9) 78 (1.1)
2598 (6.3) 22 819 (55.4) 15 655 (38.0) 116 (0.3)
2369 (6.3) 20 929 (55.6) 14 250 (37.9) 89 (0.2)
229 (6.5) 1890 (53.2) 1405 (39.6) 27 (0.8)
2135 (6.3) 18 972 (55.8) 12 795 (37.7) 73 (0.2)
463 (6.4) 3847 (53.3) 2860 (39.7) 43 (0.6)
*Obtained from the birth record. †Obtained from the first survey (at age 6 mo).
care of children were queried in the third survey (at age 2.5 years), and we assumed that children who cared for by nursery teachers to be attending day care. Maternal smoking status was ascertained at the first survey. The presence of concern or worry regarding raising children was also queried at the first survey and categorized as much, some, and little. Maternal educational attainment was obtained from the second survey (at age 18 months). We reclassified the original 8 categories into 4 as follows: junior high school or others, high school, junior college (2 years) or vocational school, and university (4 years) or higher. The mother’s income earned from work during the year of the child’s birth was queried at the second survey, so a mother with income was assumed to be working. We excluded missing cases and conducted our analyses with complete cases. In the sensitivity analyses, we further adjusted for the following variables in addition to the same set of covariates in model 3: paternal annual income during the year of the child’s birth, obtained at the second survey (as a continuous variable); whether parents made a conscious effort to talk to the child, as an indicator of parental stimulation, obtained at the first survey (dichotomous); and the child’s tendency to become sick, obtained at the first survey (dichotomous). These variables were also considered important potential confounding variables in the previous studies.5,10,12,13,16,18 Furthermore, to reduce the likelihood of reverse causation (ie, children who have disabilities might not be able to estab-
lish breastfeeding), we excluded children who had visited a clinic or hospital for congenital disease between age 7 and 18 months and repeated the same analysis in model 3. We had no information on visits before age 6 months. All CIs were calculated at the 95% level. Stata SE version 12 (StataCorp, College Station, Texas) was used for all analyses. This study was approved by the Institutional Review Board of the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences (#486).
Results Table I presents baseline characteristics from the birth record and the first survey of eligible children, children included in the analysis, and children lost to follow-up. Among the eligible children, more than 22% were in the exclusive breastfeeding category, and only 5.9% were in the formula feeding category. Compared with the eligible children, children who were lost to follow-up between the first and third surveys were more likely to have been formula-fed and to have mothers who smoked. The same tendency was observed for children who were lost to follow-up between the first and sixth surveys. Table II presents the demographic characteristics of the children included in the analysis at age 2.5 years according to infant feeding practice. Compared with children who had been formula fed, children in the exclusive breastfeeding
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Table II. Demographic characteristics of children included in the analysis at age 2.5 years according to infant feeding practice (n = 37 637)
Characteristics of children Sex, n (%)* Boys Girls Mean birth weight, g (SD)* Presence of a sibling, n (%)* 0 $1 Day care attendance, n (%)† No Yes Parental characteristics Mean maternal age at delivery, y (SD)* Maternal educational attainment, n (%)z University or higher Junior college High school Junior high school or other Missing Maternal smoking status, n (%)x Nonsmoker Smoker Unknown Maternal working status, n (%)z No Yes Missing Presence of concern or worry regarding raising children, n (%)x Much Some Little Unknown
Partial breastfeeding, breastfeeding duration
Formula feeding (n = 2102)
1-2 mo (n = 7003)
3-5 mo (n = 7398)
1128 (53.7) 974 (46.3) 3118 (362.0)
3684 (52.6) 3319 (47.4) 3110 (344.0)
3740 (50.6) 3658 (49.5) 3117 (337.0)
6661 (53.2) 5863 (46.8) 3124 (336.0)
4386 (50.9) 4224 (49.1) 3138 (337.0)
1026 (48.8) 1076 (51.2)
3389 (48.4) 3614 (51.6)
3857 (52.1) 3541 (47.9)
6726 (53.7) 5798 (46.3)
3444 (40.0) 5166 (60.0)
1550 (73.7) 552 (26.3)
4875 (69.6) 2128 (30.4)
5349 (72.3) 2049 (27.7)
9343 (74.6) 3181 (25.4)
6544 (76.0) 2066 (24.0)
30.1 (5.0)
29.4 (4.7)
29.7 (4.5)
30.6 (4.2)
30.3 (4.1)
127 (6.0) 628 (29.9) 1059 (50.4) 185 (8.8) 103 (4.9)
533 (7.6) 2317 (33.1) 3385 (48.3) 451 (6.4) 317 (4.5)
868 (11.7) 2941 (39.8) 3038 (41.1) 284 (3.8) 267 (3.6)
2164 (17.3) 5545 (44.3) 4235 (33.8) 286 (2.3) 294 (2.4)
1500 (17.4) 3840 (44.6) 2871 (33.3) 188 (2.2) 211 (2.5)
1494 (71.1) 585 (27.8) 23 (1.1)
4932 (70.4) 2036 (29.1) 35 (0.5)
5960 (80.6) 1402 (19.0) 36 (0.5)
11 325 (90.4) 1147 (9.2) 52 (0.4)
7914 (91.9) 665 (7.7) 31 (0.4)
483 (23.0) 1519 (72.3) 100 (4.8)
1917 (27.4) 4796 (68.5) 290 (4.1)
2003 (27.1) 5138 (69.5) 257 (3.5)
3341 (26.7) 8932 (71.3) 251 (2.0)
1889 (21.9) 6540 (76.0) 181 (2.1)
176 (8.4) 1079 (51.3) 839 (39.9) 8 (0.4)
464 (6.6) 3744 (53.5) 2777 (39.7) 18 (0.3)
446 (6.0) 4096 (55.4) 2839 (38.4) 17 (0.2)
811 (6.5) 7304 (58.3) 4385 (35.0) 24 (0.2)
472 (5.5) 4706 (54.7) 3410 (39.6) 22 (0.3)
6-7 mo (n = 12 524)
Exclusive breastfeeding (n = 8610)
*Obtained from the birth record. †Obtained from the third survey (at age 2.5 y). zObtained from the second survey (at age 18 mo). xObtained from the first survey (at age 6 mo).
category were more likely to have siblings, mothers with higher academic attainment, nonsmoking mothers, and parents with few concerns regarding raising children. The same tendencies were observed for children included in the analysis at age 5.5 years (Table III; available at www.jpeds. com). Table IV presents associations between infant feeding practice at age 6-7 months and behavioral development outcomes at age 2.5 years. Children who were breastfed were less likely to demonstrate developmental delays in behavior, such as being unable to climb stairs or to say his or her own name. Even after adjusting for all covariates (model 3), the protective associations remained for exclusive breastfeeding as well as for partial breastfeeding with a longer duration of breastfeeding, and most of the ORs for exclusive breastfeeding were smaller than those for partial breastfeeding. For example, compared with the formula-fed group, the OR for being unable to say his or her own name were 0.61 (95% CI, 0.53-0.71) for exclusive breastfeeding, compared with 0.66 (95% CI, 0.57-0.77) for partial breastfeeding with breastfeeding duration of 6-7 months, 0.85 (95% CI, 0.73-0.99) with duration of 1022
3-5 months, and 0.83 (95% CI, 0.72-0.97) with duration of 1-2 months. We also observed a dose–response relationship between breastfeeding status and the inability to perform ageappropriate behaviors at age 5.5 years (Table V). For example, compared with the formula-fed group, the ORs for inability to listen without fidgeting were 0.64 (95% CI, 0.56-0.73) for exclusive breastfeeding, 0.74 (95% CI, 0.66-0.85) for partial breastfeeding with breastfeeding duration of 6-7 months, 0.79 (95% CI, 0.69-0.90) for partial breastfeeding with breastfeeding duration of 3-5 months, and 0.95 (95% CI, 0.84-1.09) for partial breastfeeding with breastfeeding duration of 1-2 months. In the sensitivity analyses, even after further adjustment for paternal income, the indicator of parental stimulation, or the child’s tendency to become sick, as well as the covariates in model 3, the main findings did not change substantially (Tables VI and VII; available at www.jpeds.com). In addition, 745 children with congenital disease were excluded from the further sensitivity analyses at age 2.5 years, and 676 such children were excluded at age Yorifuji et al
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Table IV. Associations of infant feeding practice with behavioral development at age 2.5 years Cases with behavioral problems, n (%) Unable to climb stairs Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to compose a 2-phrase sentence Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to say his or her own name Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to use a spoon to eat Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo
Model 1: Crude model
Model 2: Adjusted model*
Model 3: Fully adjusted model†
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 37 411)z 1 (ref)
(n = 37 411) 1 (ref)
(n = 35 991) 1 (ref)
0.68 (0.50-0.92) 0.66 (0.49-0.90) 0.53 (0.40-0.71) 0.50 (0.37-0.68) (n = 37 047) 1 (ref)
0.68 (0.50-0.93) 0.65 (0.48-0.88) 0.51 (0.38-0.69) 0.53 (0.39-0.73) (n = 37 047) 1 (ref)
0.69 (0.50-0.94) 0.64 (0.47-0.88) 0.49 (0.36-0.66) 0.52 (0.38-0.72) (n = 35 991) 1 (ref)
0.71 (0.57-0.87) 0.68 (0.55-0.83) 0.53 (0.43-0.65) 0.43 (0.35-0.54) (n = 37 371) 1 (ref)
0.73 (0.59-0.91) 0.70 (0.56-0.86) 0.52 (0.42-0.64) 0.44 (0.35-0.55) (n = 37 371) 1 (ref)
0.74 (0.59-0.92) 0.71 (0.57-0.89) 0.50 (0.41-0.63) 0.43 (0.34-0.55) (n = 35 952) 1 (ref)
52 (2.5)
0.75 (0.65-0.87) 0.76 (0.66-0.87) 0.65 (0.57-0.74) 0.59 (0.51-0.68) (n = 37 424)z 1 (ref)
0.77 (0.67-0.89) 0.78 (0.68-0.90) 0.63 (0.55-0.73) 0.58 (0.50-0.67) (n = 37 424) 1 (ref)
0.83 (0.72-0.97) 0.85 (0.73-0.99) 0.66 (0.57-0.77) 0.61 (0.53-0.71) (n = 36 006) 1 (ref)
117 (1.7) 144 (2.0) 225 (1.8) 114 (1.3)
0.67 (0.48-0.93) 0.78 (0.57-1.07) 0.72 (0.53-0.97) 0.53 (0.38-0.73)
0.71 (0.51-0.99) 0.81 (0.58-1.12) 0.70 (0.52-0.96) 0.58 (0.41-0.80)
0.76 (0.54-1.08) 0.85 (0.60-1.19) 0.69 (0.50-0.96) 0.58 (0.40-0.82)
61 (2.9) 139 (2.0) 144 (2.0) 196 (1.6) 127 (1.5) 127 (6.0) 305 (4.4) 309 (4.2) 414 (3.3) 235 (2.7) 311 (14.8) 811 (11.6) 865 (11.7) 1270 (10.1) 804 (9.3)
*Adjusted for child factors (sex, birth weight, presence of a sibling, and day care attendance). †Adjusted for child factors as well as parental factors (maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). zNumber of included cases in each analysis.
5.5 years. The protective effects were slightly attenuated at age 2.5 years, but the main findings did not change substantially (Tables VI and VII).
Discussion In the present study, we prospectively examined associations between breastfeeding (data obtained at age 67 months) and behavioral development outcomes at age 2.5 and 5.5 years using a large Japanese nationwide population-based longitudinal survey. We observed a clear dose–response relationship between breastfeeding status and the inability to perform age-appropriate developmental behavior skills surveyed at both ages. The protective associations did not change even after we adjusted for an extensive list of potential confounders or in the sensitivity analyses. This is the largest published study to date examining the association between breastfeeding and behavioral development. Behavioral development outcomes at age 2.5 years are related to gross and fine motor development, as well as to verbal development. We observed protective effects on these outcomes with longer duration of breastfeeding. This finding is consistent with previous studies demonstrating potential benefits for motor and verbal development.8,13,23-26 The present study supports those previous findings with a large sam-
ple size, a clear dose–response relationship, and adjustment for a number of potential confounders. We also observed protective effects of breastfeeding on behavioral development at age 5.5 years, related to social and self-regulatory development. Previous observational studies similarly demonstrated potential benefits on these behavioral developments, including adaptability or communication at age 1 year,13 attention-hyperactivity behaviors and social behavior at age 4 years,11 behavior scores for 5 areas of child behavior at age 5 years,10 and behaviors obtained by the Child Behavior Checklist at age 14 years.12 The large RCT in Belarus mentioned earlier found no protective effect on social and self-regulatory behavior at age 6.5 years in an intention-to-treat analysis comparing a breastfeeding promotion group and a control group.18,19 Although we cannot totally exclude the possibility of residual confounding in our study or previous observational studies, the RCT also may suffer from nondifferential exposure misclassification between the 2 groups, possibly moving effect estimates toward the null, attenuating the results.27 An absence of association in the RCT does not nullify all of the findings observed in the observational studies. Based on our data, we believe that there are at least 3 reasons for the protective effects of breastfeeding on behavioral development. First, the biological ingredients of breast milk may play a role. Breast milk contains long-chain
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Table V. Associations of infant feeding practice with behavioral development at age 5.5 years Cases with a behavioral problem, n (%) Unable to listen without fidgeting Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to focus on one task Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to remain patient Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to express emotions Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to act in a group Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to keep promises Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo
Model 1: Crude model
Model 2: Adjusted model*
Model 3: Fully adjusted model†
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 33 473)z 1 (ref)
(n = 33 473) 1 (ref)
(n = 32 588) 1 (ref)
0.95 (0.83-1.07) 0.75 (0.66-0.85) 0.68 (0.60-0.77) 0.53 (0.47-0.60) (n = 33 525) 1 (ref)
0.96 (0.84-1.09) 0.75 (0.66-0.86) 0.66 (0.59-0.75) 0.56 (0.49-0.63) (n = 33 525) 1 (ref)
0.95 (0.84-1.09) 0.79 (0.69-0.90) 0.74 (0.66-0.85) 0.64 (0.56-0.73) (n = 32 640) 1 (ref)
0.86 (0.75-1.00) 0.80 (0.69-0.92) 0.66 (0.58-0.76) 0.52 (0.45-0.60) (n = 33 349) 1 (ref)
0.87 (0.75-1.00) 0.79 (0.68-0.91) 0.65 (0.56-0.74) 0.54 (0.47-0.63) (n = 33 349) 1 (ref)
0.88 (0.76-1.02) 0.86 (0.74-0.99) 0.76 (0.66-0.87) 0.65 (0.56-0.75) (n = 32 467) 1 (ref)
0.80 (0.71-0.89) 0.72 (0.64-0.80) 0.62 (0.56-0.69) 0.54 (0.48-0.61) (n = 33 320)z 1 (ref)
0.80 (0.71-0.90) 0.73 (0.65-0.82) 0.63 (0.56-0.70) 0.54 (0.48-0.60) (n = 33 320) 1 (ref)
0.81 (0.72-0.92) 0.77 (0.69-0.87) 0.68 (0.61-0.76) 0.60 (0.53-0.67) (n = 32 441) 1 (ref)
0.84 (0.74-0.95) 0.90 (0.80-1.02) 0.84 (0.75-0.95) 0.72 (0.64-0.81) (n = 33 475) 1 (ref)
0.84 (0.75-0.95) 0.90 (0.80-1.02) 0.83 (0.74-0.93) 0.75 (0.67-0.85) (n = 33 475) 1 (ref)
0.84 (0.74-0.96) 0.92 (0.81-1.04) 0.84 (0.74-0.94) 0.76 (0.67-0.86) (n = 32 593) 1 (ref)
469 (25.4)
0.85 (0.70-1.02) 0.72 (0.59-0.87) 0.61 (0.51-0.73) 0.57 (0.47-0.68) (n = 33 171) 1 (ref)
0.86 (0.71-1.03) 0.73 (0.60-0.88) 0.60 (0.50-0.72) 0.59 (0.49-0.72) (n = 33 171) 1 (ref)
0.86 (0.71-1.04) 0.75 (0.62-0.91) 0.64 (0.53-0.77) 0.63 (0.51-0.76) (n = 32 297) 1 (ref)
1368 (22.3) 1320 (19.9) 2028 (17.7) 1235 (15.7)
0.84 (0.74-0.94) 0.72 (0.64-0.82) 0.63 (0.56-0.70) 0.54 (0.48-0.61)
0.84 (0.74-0.95) 0.73 (0.64-0.82) 0.62 (0.55-0.70) 0.56 (0.49-0.63)
0.83 (0.73-0.94) 0.77 (0.68-0.87) 0.70 (0.62-0.79) 0.63 (0.56-0.72)
413 (22.4) 1319 (21.5) 1182 (17.8) 1885 (16.4) 1052 (13.4) 312 (16.9) 919 (15.0) 930 (14.0) 1364 (11.9) 760 (9.7) 596 (32.3) 1694 (27.6) 1696 (25.6) 2645 (23.0) 1624 (20.6) 466 (25.2) 1363 (22.2) 1555 (23.5) 2560 (22.3) 1547 (19.6) 160 (8.7) 460 (7.5) 428 (6.5) 634 (5.5) 406 (5.2)
*Adjusted for child factors (sex, birth weight, and presence of a sibling). †Adjusted for child factors as well as parental factors (maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). zNumber of included cases in each analysis.
polyunsaturated fatty acids, particularly docosahexaenoic acid and arachidonic acid, which are considered to be positively associated with cognitive and behavioral functions.28 Although formula milk in Japan has been supplemented with docosahexaenoic acid or arachidonic acid in recent years, the levels of these fatty acids did not reach those provided by breastfeeding in 2001. Second, mothers who breastfeed are likely to spend more time with their babies than those who formula feed. Extensive interactions through breastfeeding may have promoted the shaping of brain circuitry in the infant as well as developing strong mother–infant bonding, which creates the foundation for later development.29 Third, there is the possibility of a biased association because of residual confounding. We extensively adjusted for potential confounders in the main analyses, however. 1024
Furthermore, we examined other potential confounders in the sensitivity analyses and found no significant change in the results. Thus, it is unlikely that our present findings can be totally attributed to residual confounding. A strength of the present study is the large, nationally representative sample. Roughly one-twentieth of the children born in Japan in 2001 are included in this survey. The large sample size allowed us to examine the dose–response relationship between breastfeeding and behavioral development outcomes. In addition, the very high response rate at baseline strengthens the validity of our findings. The duration of breastfeeding should be accurate, because the information on feeding practice was collected at the first survey (ie, when the children were aged 6-7 months); however, we could not evaluate the effect of both partial and exclusive breastfeeding beyond 6-7 months. Yorifuji et al
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May 2014 The uncertainty of the external validation of questions used to assess the behavioral outcomes poses a threat to the validity of our findings. Moreover, because of the subjective nature of these questions, we cannot exclude the possibility of misclassification of behavioral outcomes. Any misclassification would be nondifferential, however, moving the effect estimates toward the null. Loss to follow-up may be a concern. Because loss was more common in higher-risk groups, such as formula-fed children and mothers who smoked, we may be underestimating the protective effects of breastfeeding on developmental outcomes. Finally, a reverse causation (ie, children who originally had disabilities might not be able to establish breastfeeding) would be unlikely, because the findings were robust in the sensitivity analyses, which excluded children with congenital disease. In conclusion, although we are not certain whether a biological ingredient of breast milk, extensive mother–child interactions through breastfeeding, or both are beneficial, we observed prolonged effects of breastfeeding on developmental behavior skills surveyed at age 2.5 and 5.5 years. n We appreciate valuable comments by Dr Satoshi Sanada and Ms Midory Higa Diez. We thank Ms Saori Irie for her support. Submitted for publication Sep 27, 2013; last revision received Dec 10, 2013; accepted Jan 7, 2014. Reprint requests: Takashi Yorifuji, MD, PhD, Department of Human Ecology, Okayama University Graduate School of Environmental and Life Science, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. E-mail: yorichan@ md.okayama-u.ac.jp
References 1. World Health Organization. Global strategy for infant and young child feeding: the optimal duration of exclusive breastfeeding. Geneva, Switzerland: World Health Organization; 2001. 2. Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev 2012;CD003517. 3. Quigley MA, Kelly YJ, Sacker A. Breastfeeding and hospitalization for diarrheal and respiratory infection in the United Kingdom Millennium Cohort Study. Pediatrics 2007;119:e837-42. 4. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. Lancet 2000;355:451-5. 5. Horta B, Victor C. Long-term effects of breastfeeding: A systematic review. Geneva, Switzerland: World Health Organization; 2013. 6. Britton JR, Britton HL, Gronwaldt V. Breastfeeding, sensitivity, and attachment. Pediatrics 2006;118:e1436-43. 7. Anderson JW, Johnstone BM, Remley DT. Breast-feeding and cognitive development: a meta-analysis. Am J Clin Nutr 1999;70:525-35. 8. Eickmann SH, de Lira PI, Lima Mde C, Coutinho SB, Teixeira Mde L, Ashworth A. Breast feeding and mental and motor development at 12 months in a low-income population in northeast Brazil. Paediatr Perinat Epidemiol 2007;21:129-37. 9. Hart S, Boylan LM, Carroll S, Musick YA, Lampe RM. Brief report: breast-fed one-week-olds demonstrate superior neurobehavioral organization. J Pediatr Psychol 2003;28:529-34.
10. Heikkila K, Sacker A, Kelly Y, Renfrew MJ, Quigley MA. Breast feeding and child behaviour in the Millennium Cohort Study. Arch Dis Child 2011;96:635-42. 11. Julvez J, Ribas-Fito N, Forns M, Garcia-Esteban R, Torrent M, Sunyer J. Attention behaviour and hyperactivity at age 4 and duration of breastfeeding. Acta Paediatr 2007;96:842-7. 12. Oddy WH, Kendall GE, Li J, Jacoby P, Robinson M, de Klerk NH, et al. The long-term effects of breastfeeding on child and adolescent mental health: a pregnancy cohort study followed for 14 years. J Pediatr 2010; 156:568-74. 13. Oddy WH, Robinson M, Kendall GE, Li J, Zubrick SR, Stanley FJ. Breastfeeding and early child development: a prospective cohort study. Acta Paediatr 2011;100:992-9. 14. Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Higgins RD, Langer JC, et al. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics 2007;120:e953-9. 15. Der G, Batty GD, Deary IJ. Effect of breast feeding on intelligence in children: prospective study, sibling pairs analysis, and meta-analysis. BMJ 2006;333:945. 16. Holme A, MacArthur C, Lancashire R. The effects of breastfeeding on cognitive and neurological development of children at 9 years. Child Care Health Dev 2010;36:583-90. 17. Kramer MS, Aboud F, Mironova E, Vanilovich I, Platt RW, Matush L, et al. Breastfeeding and child cognitive development: new evidence from a large randomized trial. Arch Gen Psychiatry 2008;65:578-84. 18. Kramer MS, Fombonne E, Matush L, Bogdanovich N, Dahhou M, Platt RW. Long-term behavioural consequences of infant feeding: the limits of observational studies. Paediatr Perinat Epidemiol 2011;25: 500-6. 19. Kramer MS, Fombonne E, Igumnov S, Vanilovich I, Matush L, Mironova E, et al. Effects of prolonged and exclusive breastfeeding on child behavior and maternal adjustment: evidence from a large, randomized trial. Pediatrics 2008;121:e435-40. 20. Yamakawa M, Yorifuji T, Inoue S, Kato T, Doi H. Breastfeeding and obesity among schoolchildren: a nationwide longitudinal survey in Japan. JAMA Pediatr 2013;167:919-25. 21. Kato T, Yorifuji T, Inoue S, Yamakawa M, Doi H, Kawachi I. Associations of preterm births with child health and development: a Japanese population-based study. J Pediatr 2013;163:1578-84. 22. Kato T, Yorifuji T, Inoue S, Doi H, Kawachi I. Association of birth length and risk of hospitalisation among full-term babies in Japan. Paediatr Perinat Epidemiol 2013;27:361-70. 23. Dee DL, Li R, Lee LC, Grummer-Strawn LM. Associations between breastfeeding practices and young children’s language and motor skill development. Pediatrics 2007;119(Suppl 1):S92-8. 24. McCrory C, Murray A. The effect of breastfeeding on neurodevelopment in infancy. Matern Child Health J 2012;17:1680-8. 25. Sacker A, Quigley MA, Kelly YJ. Breastfeeding and developmental delay: findings from the millennium cohort study. Pediatrics 2006;118:e682-9. 26. Whitehouse AJ, Robinson M, Li J, Oddy WH. Duration of breast feeding and language ability in middle childhood. Paediatr Perinat Epidemiol 2010;25:44-52. 27. Rothman KJ. Epidemiology: An introduction. 2nd ed. New York: Oxford University Press; 2012. 28. McCann JC, Ames BN. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr 2005;82:281-95. 29. National Scientific Council on the Developing Child. The timing and quality of early experiences combine to shape brain architecture: Working Paper 5; 2007. Available from: http://www.developingchild.net. Accessed July 22, 2013.
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All babies born between the 10th and 17th of January or the 10th and 17th of July in 2001 in Japan: n = 53 575
Questionnaire returned at the first survey: n = 47 015 Exclusion (n = 5125) - Children < 37 gestational weeks: n = 2418 - Birth weight < 2500 g: n = 2464 - Twins or triplets: n = 243 Feeding practice information missing (n = 702) Eligible children: n = 41 188
Lost to follow up at the third survey (n = 3551)
Lost to follow up at the sixth survey (n = 7213)
Children included in the analyses - Age 2.5 years (3rd survey): n = 37 637 - Age 5.5 years (6th survey): n = 33 975
Figure. Flow chart of study participants.
Table III. Demographic characteristics of children included in the analysis at age 5.5 years according to infant feeding practice (n = 33 975)
Characteristics of children Sex, n (%)* Boys Girls Mean birth weight, g (SD)* Presence of a sibling, n (%)* 0 $1 Parental characteristics Mean maternal age at delivery, y (SD)* Maternal educational attainment, n (%)† University or higher Junior college High school Junior high school or other Missing Maternal smoking status, n (%)z Nonsmoker Smoker Unknown Maternal working status, n (%)† No Yes Missing Presence of concern or worry regarding raising children, n (%)z Much Some Little Unknown
Partial breastfeeding, breastfeeding duration
Formula feeding (n = 1847)
1-2 mo (n = 6137)
3-5 mo (n = 6629)
1000 (54.1) 847 (45.9) 3122 (360.0)
3234 (52.7) 2903 (47.3) 3109 (344.0)
3343 (50.4) 3286 (49.6) 3115 (336.0)
6117 (53.3) 5369 (46.7) 3123 (336.0)
4014 (51.0) 3862 (49.0) 3139 (335.0)
900 (48.7) 947 (51.3)
2936 (47.8) 3201 (52.2)
3437 (51.9) 3192 (48.2)
6134 (53.4) 5352 (46.6)
3134 (39.8) 4742 (60.2)
30.3 (4.9)
29.6 (4.6)
29.9 (4.4)
30.7 (4.2)
30.4 (4.0)
118 (6.4) 569 (30.8) 949 (51.4) 148 (8.0) 63 (3.4)
497 (8.1) 2125 (34.6) 2985 (48.6) 360 (5.9) 170 (2.8)
826 (12.5) 2721 (41.1) 2706 (40.8) 218 (3.3) 158 (2.4)
2071 (18.0) 5179 (45.1) 3837 (33.4) 226 (2.0) 173 (1.5)
1420 (18.0) 3587 (45.5) 2583 (32.8) 154 (2.0) 132 (1.7)
1341 (72.6) 487 (26.4) 19 (1.0)
4431 (72.2) 1678 (27.3) 28 (0.5)
5414 (81.7) 1182 (17.8) 33 (0.5)
10 460 (91.1) 985 (8.6) 41 (0.4)
7292 (92.6) 559 (7.1) 25 (0.3)
441 (23.9) 1347 (72.9) 59 (3.2)
1717 (28.0) 4269 (69.6) 151 (2.5)
1837 (27.7) 4644 (70.1) 148 (2.2)
3101 (27.0) 8251 (71.8) 134 (1.2)
1765 (22.4) 6006 (76.3) 105 (1.3)
150 (8.1) 961 (52.0) 732 (39.6) 4 (0.2)
408 (6.7) 3288 (53.6) 2427 (39.6) 14 (0.2)
402 (6.1) 3699 (55.8) 2512 (37.9) 16 (0.2)
733 (6.4) 6728 (58.6) 4006 (34.9) 19 (0.2)
442 (5.6) 4296 (54.6) 3118 (39.6) 20 (0.3)
6-7 mo (n = 11 486)
Exclusive breastfeeding (n = 7876)
*Obtained from the birth record. †Obtained from the second survey (at age 18 mo). zObtained from the first survey (at age 6 mo).
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Table VI. Sensitivity analyses at age 2.5 years Model 3* plus paternal Model 3* plus parental Model 3* plus child tendency Model 3* (Exclusion of children income† stimulation† to become sick† with congenital disease) OR (95% CI) Unable to climb stairs (n = 35 377)z Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.69 (0.50-0.95) 3-5 mo 0.65 (0.47-0.89) 6-7 mo 0.48 (0.36-0.65) Exclusive breastfeeding at age 6-7 mo 0.54 (0.39-0.74) Unable to compose a 2-phrase sentence (n = 35 378) Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.73 (0.58-0.91) 3-5 mo 0.71 (0.57-0.89) 6-7 mo 0.50 (0.41-0.63) Exclusive breastfeeding at age 6-7 mo 0.43 (0.34-0.54) Unable to say his or her own name (n = 35 339) Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.83 (0.71-0.96) 3-5 mo 0.85 (0.73-0.99) 6-7 mo 0.66 (0.57-0.76) Exclusive breastfeeding at age 6-7 mo 0.61 (0.52-0.71) Unable to use a spoon to eat (n = 35 394)z Formula feeding 1 (ref) Partial breastfeeding, breastfeeding duration 1-2 mo 0.75 (0.53-1.06) 3-5 mo 0.84 (0.60-1.18) 6-7 mo 0.69 (0.50-0.95) Exclusive breastfeeding at age 6-7 mo 0.58 (0.40-0.82)
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 35 991) 1 (ref)
(n = 35 991) 1 (ref)
(n = 35 258) 1 (ref)
0.69 (0.51-0.94) 0.65 (0.47-0.88) 0.49 (0.36-0.66) 0.53 (0.38-0.73) (n = 35 991) 1 (ref)
0.70 (0.51-0.95) 0.65 (0.48-0.89) 0.50 (0.37-0.68) 0.55 (0.40-0.75) (n = 35 991) 1 (ref)
0.73 (0.51-1.04) 0.80 (0.57-1.14) 0.62 (0.44-0.87) 0.68 (0.48-0.97) (n = 35 259) 1 (ref)
0.75 (0.60-0.93) 0.72 (0.57-0.89) 0.51 (0.41-0.63) 0.44 (0.35-0.55) (n = 35 952) 1 (ref)
0.74 (0.60-0.93) 0.71 (0.57-0.89) 0.51 (0.41-0.64) 0.44 (0.35-0.56) (n = 35 952) 1 (ref)
0.76 (0.60-0.96) 0.77 (0.61-0.98) 0.57 (0.45-0.71) 0.49 (0.39-0.63) (n = 35 221) 1 (ref)
0.84 (0.72-0.98) 0.86 (0.74-1.00) 0.67 (0.58-0.78) 0.62 (0.53-0.72) (n = 36 006) 1 (ref)
0.84 (0.72-0.97) 0.85 (0.73-0.99) 0.67 (0.58-0.77) 0.62 (0.53-0.72) (n = 36 006) 1 (ref)
0.84 (0.72-0.99) 0.88 (0.76-1.03) 0.69 (0.59-0.80) 0.65 (0.55-0.76) (n = 35 273) 1 (ref)
0.77 (0.54-1.09) 0.85 (0.61-1.20) 0.70 (0.51-0.97) 0.58 (0.41-0.83)
0.77 (0.54-1.09) 0.86 (0.61-1.21) 0.72 (0.52-0.99) 0.60 (0.42-0.85)
0.86 (0.58-1.26) 1.04 (0.71-1.51) 0.87 (0.60-1.24) 0.74 (0.50-1.09)
*Adjusted for child factors as well as parental factors (sex, birth weight, presence of a sibling, day care attendance, maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). †Further adjusted for each variable in the fully adjusted model (model 3). zNumber of included cases in each analysis.
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Table VII. Sensitivity analyses at age 5.5 years Model 3* plus paternal income†
Model 3* plus parental stimulation†
Model 3* plus child tendency to become sick†
Model 3* (exclusion of children with congenital disease)
Unable to listen carefully Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to focus on one task Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to remain patient Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to express emotions Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to act in a group Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo Unable to keep promises Formula feeding Partial breastfeeding, breastfeeding duration 1-2 mo 3-5 mo 6-7 mo Exclusive breastfeeding at age 6-7 mo
OR (95% CI)
OR (95% CI)
OR (95% CI)
OR (95% CI)
(n = 32 064)z 1 (ref)
(n = 32 588) 1 (ref)
(n = 32 588) 1 (ref)
(n = 31 936) 1 (ref)
0.95 (0.83-1.08) 0.79 (0.69-0.90) 0.74 (0.65-0.84) 0.63 (0.55-0.72) (n = 32 118) 1 (ref)
0.96 (0.84-1.10) 0.80 (0.70-0.91) 0.75 (0.66-0.85) 0.65 (0.56-0.74) (n = 32 640) 1 (ref)
0.96 (0.84-1.09) 0.79 (0.69-0.90) 0.75 (0.66-0.85) 0.64 (0.56-0.73) (n = 32 640) 1 (ref)
0.96 (0.84-1.10) 0.80 (0.70-0.91) 0.75 (0.66-0.85) 0.65 (0.56-0.74) (n = 31 985) 1 (ref)
0.86 (0.75-1.00) 0.85 (0.73-0.99) 0.75 (0.65-0.86) 0.64 (0.55-0.74) (n = 31 947) 1 (ref)
0.89 (0.77-1.02) 0.86 (0.75-1.00) 0.76 (0.66-0.88) 0.65 (0.56-0.76) (n = 32 467) 1 (ref)
0.88 (0.76-1.02) 0.86 (0.74-0.99) 0.76 (0.66-0.87) 0.65 (0.56-0.75) (n = 32 467) 1 (ref)
0.90 (0.78-1.05) 0.88 (0.76-1.02) 0.77 (0.66-0.88) 0.66 (0.57-0.77) (n = 31 818) 1 (ref)
0.81 (0.72-0.91) 0.77 (0.69-0.87) 0.67 (0.60-0.75) 0.59 (0.53-0.67) (n = 31 919)z 1 (ref)
0.82 (0.73-0.92) 0.78 (0.69-0.87) 0.68 (0.61-0.76) 0.60 (0.54-0.68) (n = 32 441) 1 (ref)
0.82 (0.73-0.92) 0.77 (0.69-0.87) 0.68 (0.61-0.76) 0.60 (0.53-0.68) (n = 32 441) 1 (ref)
0.82 (0.72-0.92) 0.78 (0.69-0.87) 0.68 (0.60-0.76) 0.60 (0.53-0.68) (n = 31 785) 1 (ref)
0.86 (0.75-0.97) 0.93 (0.82-1.05) 0.85 (0.75-0.95) 0.77 (0.68-0.88) (n = 32 073) 1 (ref)
0.85 (0.75-0.96) 0.92 (0.82-1.05) 0.85 (0.75-0.96) 0.77 (0.68-0.87) (n = 32 593) 1 (ref)
0.84 (0.74-0.96) 0.92 (0.81-1.04) 0.84 (0.75-0.95) 0.76 (0.67-0.86) (n = 32 593) 1 (ref)
0.86 (0.75-0.97) 0.93 (0.82-1.05) 0.85 (0.76-0.96) 0.77 (0.68-0.88) (n = 31 932) 1 (ref)
0.86 (0.70-1.04) 0.75 (0.61-0.91) 0.64 (0.52-0.77) 0.62 (0.51-0.76) (n = 31 779) 1 (ref)
0.87 (0.71-1.05) 0.76 (0.63-0.93) 0.65 (0.54-0.79) 0.64 (0.52-0.78) (n = 32 297) 1 (ref)
0.86 (0.71-1.05) 0.76 (0.62-0.92) 0.65 (0.54-0.78) 0.63 (0.52-0.77) (n = 32 297) 1 (ref)
0.88 (0.72-1.07) 0.78 (0.63-0.95) 0.68 (0.56-0.83) 0.67 (0.55-0.83) (n = 31 645) 1 (ref)
0.82 (0.72-0.93) 0.77 (0.68-0.87) 0.69 (0.61-0.78) 0.63 (0.55-0.72)
0.84 (0.74-0.95) 0.77 (0.68-0.88) 0.70 (0.62-0.79) 0.64 (0.56-0.72)
0.83 (0.73-0.94) 0.77 (0.68-0.87) 0.70 (0.62-0.79) 0.63 (0.56-0.72)
0.83 (0.73-0.94) 0.77 (0.68-0.87) 0.69 (0.61-0.78) 0.63 (0.56-0.72)
*Adjusted for child factors as well as parental factors (sex, birth weight, presence of a sibling, maternal educational attainment, maternal smoking status, maternal age at delivery, maternal working status, and parental concern or worry regarding raising children). †Further adjusted for each variable in the fully adjusted model (model 3). zNumber of included cases in each analysis.
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